\r\n\t
\r\n\tComputer graphics are not entirely an original topic, because it defines and solves problems using some already established techniques such as geometry, algebra, optics, and psychology. The geometry provides a framework for describing 2D and 3D space, while the algebraic methods are used for defining and evaluating equality related to the specific space. The science of optics enables the application of the model for the description of the behavior of light, while psychology provides models for visualization and color perception.
\r\n\t
\r\n\t3D computer graphics (or 3D graphics, three-dimensional computer graphics, three-dimensional graphics) is a term describing the different methods of creating and displaying three-dimensional objects by using computer graphics.
\r\n\tThe first types of graphic interpretations were put in the plane (two-dimensional 2D). Requirements for a universal interpretation led to a three-dimensional (3D) interpretation content. From these creations have arisen applied mathematics and information disciplines of graphic interpretation of content - computer graphics. It relies on the principles of Mathematics, Descriptive Geometry, Computer Science and Applied Electronics.
\r\n\t
\r\n\t3D computer graphics or three-dimensional computer graphics use a three-dimensional representation of geometric data (often in terms of the Cartesian coordinate system) that is stored on a computer for the purpose of doing the calculation and creating 2D images. The images that are made can be stored for later use (probably as animation) or can be displayed in real-time.
\r\n\t
\r\n\tObjects within the 3D computer graphics are often called 3D models. Unlike rendered (generated) images, data that are ""tied"" to the model are inside graphic files. The 3D model is a mathematical representation of a random three-dimensional object. The model can be displayed visually as a two-dimensional image through a process called 3D rendering or can be used in non-graphical computer simulations and calculations. With 3D printing, models can be presented in real physical form.
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\r\n\tComputer graphics have remained one of the most interesting areas of modern technology, and it is the area that progresses the fastest. It has become an integral part of both application software, and computer systems in general. Computer graphics is routinely applied in the design of many products, simulators for training, production of music videos and television commercials, in movies, in data analysis, in scientific studies, in medical procedures, and in many other fields.
As markets become more global and competition intensifies, firms are beginning to realize that competition is not exclusively a firm versus firm domain, but a supply chain against supply chain phenomenon (***a, 2008). Under these circumstances, an increasing strategic importance to any organization independent of size or of sector is to deliver information, goods and services in full, on time and error-free to customers.
Radio Frequency Identification (RFID) technology represents one of a number of possible solutions to enhance supply chain. RFID technology permits the unique identification of each container, pallet, case and item to be manufactured, shipped and sold, thus allowing an increased visibility throughout the supply chain. Also, an RFID anti-counterfeiting mechanism could be implemented.
This chapter focuses on how RFID technology can be used to solve problems faced by supply chain, such as track and traceability, anti-counterfeiting. It proposes a track-and-trace anti-counterfeiting system using RFID technology. The submitted system (hereinafter referred to as ATPROD system) is aimed at relatively high-end consumer products, and it helps protect genuine products by maintaining the product pedigree and the supply chain integrity. Our system integrates mobile systems to extend corporate data outwards to mobile devices for viewing and querying. Also, users can use any mobile device endowed with an RFID reader for data collection. In this way, manual entry data has been eliminated. Moreover, users can read the tags wherever the items are placed, which enables a more flexible storage environment and an efficiency increase of supply chains and anti-counterfeiting.
We developed an RFID embedded system based on an eBox with an RFID reader attached. This system, named MICC (Interfacing, Command and Control Module), enables many applications to run at the same time as concurrent processes.
Each entry or/and exit gate of the warehouse in a supply chain could be managed by a MICC module. If there are multiple gates the installed MICC modules (from warehouse or company) could be linked together into a network.
From a functional perspective, the MICC module must meet the following requirements: to read/write data on RFID tags attached to items passing through a gate, to manage a large number of RFID tags passing through a gate at the same time, to provide data transmission via the network to a central server, to process local data and to provide the possibility of online and offline operation, as well as a set of commands in order to adapt it to a range of applications by software configurations.
From a hardware perspective, the MICC module is an embedded device, built around Vortex86SX SoC (System on Chip) device. This device integrates an x86 processor, different input/output interfaces (RS-232, parallel, USB, GPIO), BIOS, power management, MTBF counter, LoC (LAN on Chip), JTAG on the same chip. Two versions of MICC module have been designed and developed: MICC01 - without VGA output and MICC02 with VGA output. The RFID reader could be directly connected to the eBox using the USB or serial port. As for the operating system employed, each module runs Windows CE 6.0, which can perform real-time operations.
An OPC (OLE for process control) data server will run on a MICC module. This server is designed according to OPC specifications and can be a possible support for RFID middleware. The OPC data server ensures communication with the RFID reader/writer and sends information to the central database.
Thus, the application from the MICC module will be developed as an OPC data server that will communicate via RS232 or USB with RFID reader/writer. The communication between data server and RFID reader is based on a communication model that uses real-time capabilities of the operating system. This communication model allows the management of a large number of tags at the same time.
The developed system offers a good price-performance ratio. Also, it will satisfy a large number of customer requirements for fields such as industry, retail, supply chain, logistics etc.
The MICC module is designed as a component of an RFID-based authentication and track & trace system for supply chains. This subchapter displays a short description of this system.
The main role of the system is to authenticate well-known brand products. Such authentication is carried out at various points within the supply chain (starting with the manufacturer, up to the end user). The secondary function of the system is to track and trace products.
Each product has an RFID tag (also named transponder) attached to it. An RFID tag has a factory-programmed identification code stored in a non-volatile memory. This tag also provides a limited capacity memory that is used to store required information. Thus, an RFID tag could store data concerning the trace of the product to which the tag is attached (for every point of the trace; such information will also be sent to the manufacturer’s server).
Operationally, product authentication and track & trace can be structured on three levels (see Fig. 1): manufacturer, distributor and retailer. At the manufacturer’s level, there is a server by which product authentication is performed.
At the manufacturer’s level, each manufactured product will have an attached tag that identifies the product (at the encasement phase). This tag may display initial information (manufacturer, product code, manufacturing date, warranty period, server’s address where authentication of products can be performed, or any other information). If a product needs special transport and storage conditions, the RFID tag may hold a temperature sensor and memory, in order to carry out temperature logger (automatic data recorder), which will include data read from the temperature sensor. Also, at this level, products can be grouped into packages or pallets.
Authentication and track and trace of products from manufacturer to end user customer
At the distributor’s level, when a product is received into the warehouse, the information saved on the attached RFID tag will be read and sent to the manufacturer (if authentication is required). To accomplish the authentication process, a comparison is carried out between the information received from the distributor and the information from the manufacturer (stored in the manufacturer’s database server). The distributor receives the results of this comparison. If the authentication process confirms the product’s origin, then the data regarding product reception into the distributor’s warehouse will be automatically written to the product tag. Since distributors can be organized on three levels (international, national and regional), products or packages can be transported to any other distributor or retail dealer in the supply chain.
In retail, when products are received into the warehouse, authentication can be performed in the same manner as at the distributor’s level. Afterwards, the RFID tag attached to the product can be destroyed or kept attached to the product in order to preserve product ID for future maintenance.
The operational model proposed in this chapter aims to authenticate, track and trace products, starting from their manufacturing phase up to their selling to end users (Fig. 1). The ATPROD system may also be developed in order to track and trace products, until they reach a recycling center. Block diagram and hardware elements are illustrated as follows:
Fig. 2 emphasizes the general hardware architecture of the operational model, at one of points in the supply chain where a pallet/product passes: manufacturing, distribution or retail. Elements illustrated in the block diagram are the following: RFID tags attached to products and pallets, RFID readers, MICCs (Interface, Command and Control Module), PCs used in order to process information read from RFID tags and to authenticate products in accordance to this information; firewall and/or router used to secure Internet connection, manufacturer’s server – installed at the manufacturer’s level for each manufacturer, PCs provided in order to read information associated to each product, MICC. The MICC module will be used in order to process information read from RFID tags, to authenticate the products according to this data, as well as to write the product tag and send information to the manufacturer’s database server.
For each manufacturer, a central server is employed to store data specific to each product. This server will be connected to the Internet (and protected by a firewall), and used to perform authentication. All PCs connected to the Internet can connect to this server, through a password and security certificate, to access information about products of a specific manufacturer.
Pallets and/or products are provided with RFID tags. Information stored on these tags is read/written/updated by RFID readers. Readers are connected by a serial port or USB port to PC or MICC module, which controls and processes information read from RFID tags. By means of these connections, the MICC modules should receive information read from RFID tags; the modules should also transmit new information to be written on the RFID tags. The ATPROD system should operate on 13.56 MHz and should allow multiple tag readability (reading of tags attached to products included in a pallet) enabled by its anti-collision function.
MICC modules are similar, in function, to dedicated computing systems (Barr, 2007), being connected to the Internet (and protected by means of firewalls), in order to carry out the authentication of products on manufacturer’s server. Dedicated computing systems are used more often, because they center round systems designed and optimized to carry out specific tasks. In contradistinction to the general use of computing systems (personal computers), a dedicated system includes a hardware subsystem specialized and optimized to carry out the tasks for which the system was designed. Since the system is dedicated to reach specific tasks, the designers can optimize its architecture, in order to reduce its dimension and final cost.
Hardware architecture of the ATPROD system
The architecture illustrated in Fig. 2 is part of the class of dedicated architectures; these types of architectures face intensive network traffic better, the latter being specific to the infrastructures of a high number of RFID tags. A router of firewall equipment will isolate the network, and ensure data security. In this way, bandwidth is saved, which would have been otherwise busy with various passwords, authentications and other security information. Computing time is also saved, which otherwise would have been spent with different encryption/decryption methods, key generators etc.
In defining hardware architecture at unit level (manufacturer, reseller or retailer), hardware resources should be taken into consideration (storing capacity, communication interfaces, computational ability), required by the software packages used on implementing the system.
In what concerns the software, the use of OPC specifications helps improve the system (Lange et al., 2010) (Gaitan et al., 2010), as a potential support to RFID middleware. These specifications are used by many manufacturers to implement many applications of their work field. The current OPC specifications reached the maturity phase (Mahnke et al., 2009). OPC specifications allow the connection of any OPC server to any other OPC client. Several clients can be connected to the same server and a client can connect to more than one server. Thus, a server can become another server’s client, or servers can connect directly with one another. A special versatility will therefore be achieved for application configuration. These characteristics may generate a configuration of servers hierarchically connected in a tree type structure.
Clients at the level of MICC modules can also be created, in the view of configuring and local tracking, for packaging of cases, pallets or charging/discharging at docks level. If servers from other levels are clients of other servers, then servers from the last level will represent the clients of readers. The diversity and complexity of readers should be hidden by these servers. As result, they will implement a software level, often named HAL (Hardware Abstraction Level), especially to operating systems, which signifies a level of hardware abstracting. Each unit is connected to the Internet, and all units are grouped in a VPN network.
After an analysis of hardware requirements for the MICC module, its designing in accordance with SoC Vortex86SX device was proposed. Depending on functions provided by the Vortex86SX processor (***a, 2010), carrying out a MICC module is proposed. Its architecture can be seen in Fig. 3. The Vortex86SX processor (***a, 2010) is compatible with x86 family and is of a SoC type. By using this solution, Windows XP or Linux operating systems can be set up on a MICC module, where the system operates as a desktop system of limited resources. If the aim is the executing of tasks in real time, operating systems as Linux Embedded or Windows CE can be used. As illustrated in the figure, the MICC module provides 1 port of Ethernet, 3 USB ports, 2 RS232 ports, 32 programmable digital I/O (0-5V), 1 IDE port for HDD connection, an interface for connecting a CF flash card, one PS2 port for connecting mouse and keyboard, as well as one VGA output used for monitor connection.
Block diagram of MICC module
Most of the facilities provided by the MICC module are integrated on a SoC Vortex86SX chip (***a, 2010). Besides, this chip includes a DDR2 memory of 128 MB connected to Vortex86SC by a DDR2 interface, and a graphical controller XGI Volari Z9s connected to Vortex86SX by a PCI interface. After defining these requirements, printed circuit board (PCB) design can be started. Electrical circuitries can be performed for MICC02 version (with VGA port), and the MICC01 (without VGA) can be obtained by using the same PCB, on which the graphical controller and DDR2 memory used will not be mounted.
The MICC module is designed according to Vortex86SX (***a, 2010) produced by DMP company (***b, 2010). Vortex86SX is a SoC x86, manufactured by using 0.13 microns technology and a model of very low power consumption (less than 1 Watt). This intelligent SoC displays important features, such as: various interfaces of input/output (RS-232, parallel, USB or GPIO), BIOS, WatchDog type timer, management of power consumption, MTFB counter, LoC (LAN on chip), JTAG, etc., features that are not integrated on a single chip of 27x27mm (BGA-581). Vortex86SX is compatible with Windows CE, Linux and DOS operating systems. It integrates, on the same chip SoC 32KB a cache memory L1, ISA bus on 16bits, PCI bus Rev. 2.1 of 33MHz on 32 bits, SDRAM, DDR2, ROM controller, IPC (peripheral internal controllers with DMA and timer/counter of interruption included), SPI (serial peripheral interface), Fast Ethernet MAC, FIFO UART, USB 2.0 main and IDE controller.
The next step in designing the MICC module is the PCB circuit board design. We aimed to obtain a board of 11x11cm, resulting in an ergonomic MICC module of low sizes. The PCB circuit board is structured on 3 layers (Top, Middle and Bottom) of minimal width of a running wire of 10 mil (use of three layers is preferred, due to the high number of pins for Vortex86SX SoC chip). Fig. 4 illustrates the PCB circuit board for designing the MICC device.
Front and back images of the PCB
The general architecture of the ATPROD system is illustrated in Fig. 5. It is obvious that several manufacturers may co-exist in this architecture. Each of them could have more production lines, geographically distributed in more locations. The warehouses and retailers are also geographically distributed in some more locations, provided with Internet connection, in order to have access to the manufacturers’ servers and to be able to authenticate products and send information related to their traceability.
Software architecture of the ATPROD system
Each manufacturer has a central server, on which an OPC_UA_HDA_AT server runs. This server will store information regarding the products that exit the production line and are sent to the resellers’ warehouses. At the level of each distribution point, there is a PC that runs an OPC_UA_AT server. This server is able to send requests for information about the manufacturing process, as well as to save relevant information within a local database historian.
It is important to remember that this server should not be in the same location as the manufacturing points, where the only condition to be met is the existence of an Internet connection. In this way, OPC_UA_AT servers from the manufacturing points are in fact clients of the OPC_UA_HDA_AT server. Fig. 5 also illustrates the way in which the shared database is developed: for each reseller, the database is shared to all distribution points and central server.
Each warehouse is provided with a server, on which an OPC_UA_AT server runs; this server also represents a client of OPC_UA_HDA_AT associated to each producer, in order to require necessary data for authentication. The manufacturer’s server will also receive information about input of products, storing conditions or exit of products from warehouses. In what concerns the retail dealers, a PDA with an RFID reader can be used, on which a client of OPC_UA_HDA_AT servers runs. These servers are clients for OPC_UA_AT manufacturers’ servers and can be used in order to authenticate products.
ATPROD system seen from the perspective of a retail dealer
A client from a warehouse or retail dealer can send an authentication request to the manufacturer’s servers (central or local). If the needed information cannot be found within the central database server associated to the manufacturer, this will require data from a server existing in the manufacturing point. After information is achieved, it is sent to the client which has required it, in order for the client to identify products. Using such mechanism, information existing within the shared database related to the tagged products can be freely accessed.
As can be seen in Fig. 5, the shared database between manufacturers’ local servers and the central servers is illustrated in red color. For each point, a SQL database server is set up. OPC_UA_AT and OPC_UA_HDA_AT servers can access the local database by means of SQL commands.
Fig. 6 emphasizes the way a shared database can be accessed by dealers. Therefore, one or several PDA or tag-reading PCs can be provided for each dealer. It is very important that PDA devices and PCs used for authentication should be connected to the Internet, so as to make possible the access to the manufacturers’ servers. If the Internet connection of a manufacturer associated server does not work properly, the authentication of products will not be accomplished. On such computing systems, an OPC client application runs for OPC_UA_HDA_AT servers associated to each manufacturer. When a product is sold, the client application requires information from the manufacturer’s server in relation to the authentication of that product.
The requested information is sent to client application, and the authentication of product is carried out. After authentication, information concerning the selling of product is sent back to the manufacturer’s server.
Information concerning the selling of products is not erased from the database. By means of client application, the database administrator will be able to carry out erasing operations related to products sold or to create an archive with this information (for each manufacturer) that users can use at a later time.
Operationally, servers within ATPROD system are placed in two different locations: at manufacturers and in warehouses. Fig. 7 illustrates the structure of servers, as seen from the manufacturer’s perspective.
There are several RFID tagging points at each manufacturing point, and several MICC modules connected to RFID readers. The OPC servers running at these points are assigned as OPC_DA_CE_AT and their presence is justified by the necessity to label all products that exit the production line. Since MICC module should work both online and offline, a historian OPC server can also run on it; therefore, a historian will be carried out for data that should have been sent on network, but cannot be transmitted when the connection with the server is no longer active at the level of manufacturing points. OPC_UA_AT server existing at the manufacturing point level includes OPC_DA_UA_AT and OPC_HDA_UA_AT wrapper, so as to connect to OPC_DA_AT and OPC_HDA_AT servers on MICC modules. This server stores a historian with all operations performed at the manufacturing point. The central server OPC_UA_HDA_AT from the manufacturer’s level should also be a client of the OPC_UA_AT servers, at the level of manufacturing points, so as to require the necessary data. However, such data is not stored within the central server database, but within the database of manufacturing points. OPC_UA_AT servers can be replaced with OPC_NET3.0_AT servers that use WCF (Windows Communication Foundation) technology.
Placing of servers to the manufacturer site
Placing of servers to warehouses’ site
Fig. 8 emphasizes the architecture of servers as regards the warehouses. One might see that here, at the level of each system’s gate, there is a MICC module. Such a module is provided with an RFID reader, connected by RS232 serial port or USB port, in order to read/write information from RFID labels. This module runs OPC_DA_CE_AT and OPC_HDA_CE_AT servers. An OPC_UA_AT server runs on a server at the warehouse level. This server is a client of OPC_DA_CE_AT and OPC_HDA_CE_AT from MICC modules. This fact is accomplished by including the OPC_DA_UA_AT and OPC_HDA_UA_AT wrappers. In order to achieve the information necessary to product authentication, this server signifies a client of the servers existing at manufacturers’ level. Any input or output of products from the warehouse will be sent to manufacturers’ servers. In case of small distribution chains, OPC_UA servers can be replaced with OPC_NET3.0_AT servers that use the WCF (Windows Communication Foundation) technology.
Up to the present, six types of servers have been identified: OPC_DA_CE_AT, OPC_HDA_CE_AT, OPC_UA_AT, OPC_DA_UA_AT, OPC_UA_HDA_AT, OPC_NET3.0_AT.
OPC_DA_CE_AT runs on MICC modules, specific to manufactures and warehouses. This server includes a driver for the communication with RFID reader. Such a server should run on WINDOWS CE 6.0 operating system. OPC_HDA_CE_AT runs on MICC modules, specific to manufacturers and warehouses. This server is a client of OPC_DA_CE_AT server and will carry out a history if the local connection is interrupted. The server should run on WINDOWS CE 6.0 operating system. OPC_UA_AT runs at the level of manufacturing points and warehouses. It is a client of OPC_DA_CE_AT and OPC_HDA_CE_AT servers, including the OPC_DA_UA_AT and OPC_DA_UA_AT wrappers. This is also a client of OPC_UA_HDA_AT servers, at the level of manufacturers. OPC_UA_HDA_AT runs at the level of manufacturing points and centralizes all data corresponding to products circulating within the distribution chain. OPC_NET3.0_AT- emphasizes an alternative of OPC_UA_AT and OPC_UA_HDA_AT servers.
MICC module is connected by means of RS232 or USB ports to a RFID reader/writer, using 13.56 MHz frequency band and ISO 15693 standard. This module should allow the reading or writing of information on RFID tags.
One should mention that products can use two types of RFID tags: standard self-adhesive RFID tags, 13.56 frequency band, ISO 15693, variable memory (I code SLI – 896 bits, Tag-it TM HF-I - 2048 bits) and RFID tags of types: flexible card, self-adhesive, active, 13.56 MHz frequency band, ISO 15693, provided with integrated temperature sensor and temperature values history, Variosens model made by KSW Microtec, 8kbits EEPROM, which can store 1 720 values of 10 bits temperature values. All products have tags attached to them, mostly of them of first class mentioned above; those products that need special conditions of warehousing and transport can also have attached RFID tags of the second type.
Operationally, the MICC device should meet the following requirements: reading of information from RFID tags; setting up the tags so as to establish the sampling rate; if necessary, reading the temperature and storing its value into RFID tag’s memory; storing of information read from RFID tag into its own memory; sending data to central server by means of Ethernet; possibility of both on-line and off-line operations.
Fig. 9 illustrates the position of MICC module within ATPROD system. Therefore, it is placed at the input or exit of a warehouse. In what concerns the input, the MICC device reads the RFID tags attached to products that enter warehouses, sends the information read to the central server, accomplishes the authentication of products (by comparing information from tags to information existing within manufacturer’s server), and writes the information related to the input on RFID tag. When products have attached RFID tags provided with temperature sensors, the MICC module reads the history of temperatures and deletes this history from RFID tag.
MICC module operating mode
Fig. 10 also shows the UML diagram with a view to using the MICC module. From this diagram, the main two operations carried out in this module can be identified, as follows: reading of information from RFID tag, as well as writing of information on this RFID tag.
UML diagram of using MICC module
Reading of information from RFID tag is done depending upon RFID tag’s type (with or without temperature sensor). The operation of product authentication is carried out after reading information from RFID tag, and includes the connection to the manufacturer’s server, the reading of information from this server about products, and finally a comparison between this information and that provided on RFID tags. Due to this procedure, authentication of products can be performed only if the module is provided with direct connection to manufacturers’ servers.
As previously stated, data writing is performed depending upon the RFID tag under use. If an RFID tag provided with temperature sensor is used, then the sampling rate can be set up in order to save temperature values, and to empty the memory after reading the information included on RFID tag. If a classical tag is used, that is, without temperature sensor, then the tag will be written with information concerning the input or exit in or from warehouse, input/exit date, warehouse code, etc.
The application running on MICC device will be further developed in C++, under an OPC server type, able to communicate with the RFID by means of RS232 or USB. The application will be developed by using SDK package, performed after creating an image on Windows CE 6.0 (Samuel, 2008).
RFID will have significant impacts on the economy as well as on the operational and financial performance of companies in the focus areas: productivity, employment, markets, goods and services, and innovations and new products. RFID will especially generate significant impacts in applications with a unique selling proposition, e.g. anti-counterfeiting, secure supply chains, and cold chain and quality monitoring, as well as better information for decision makers.
This chapter proposes an RFID-based system to track, at the item level, material flows among partners until they reach the consumer, while maintaining data accuracy. The presented system helps small, medium companies and enterprise organizations to improve productivity and provide better service to their customers. Thus, our system has the potential of helping retailers provide the right product at the right place at the right time, allowing maximizing sales and profits.
The system is still under construction and in the near future some security aspects will also be taken into consideration.
This work was supported by the project "Computer system for controlling and checking the authenticity of products - ATPROD" - Contract no. 12082/2008, project co-funded by 2007-2013 PNCDI Program.
The periodic table comes to the mind when thinking of elements in chemistry, while organic chemistry brings to mind substances such as alcohol, aldehydes, ketones, aromatics, and other compounds based on the functional groups. Aldehydes, ketones, and carbonyl moieties are the most popular and routinely exploited functional groups in synthetic organic chemistry and in the design of organic synthesis since they render the desired synthetic manipulation and spring an easy access to complex molecular architecture. Not only in modern times but also from the times of alchemy, formaldehyde is very well utilized for embalming and preserving dead animal species by biologists; consequently, aldehyde class of compounds ranks to be the parent compounds for many other classes of compounds. Acetyl coenzyme derived from aldehyde functional group or acetaldehyde moiety is responsible for the wide variety of natural products through biosynthesis, while toward the syntheses and manufacture of chemicals on the laboratory and in industries, also the aldehyde functional group is very well synthetically manipulated. They were not only converted into structurally complex compounds through enzymes, catalysts, and thermal process, but also photons convert aldehydes into other molecular architectures by means of eminent photochemical-chemical reactions such as Norrish-type photolysis, cyclobutanol formation through Yang reaction, and [2+2] cycloaddition with alkene (Paternó-Büchi reaction). Apart from conventional catalytic way, traditional synthesis uses name reactions and photochemistry; of late, visible light is being used [1]. Apparently, solar energy is a benign, benevolent, and renewable source of energy. Visible light emerging from the source of sun promotes chemical transformations through single-electron mechanism. Basically using visible light as energy source and in the presence of catalytic amount of metal photosensitizers or organocatalysts, the chemical reactions are carried out, and this process is termed as visible-light photocatalysis and abbreviated as VLPC [2, 3]. This opens a new chapter in the textbook of organic synthesis [4]. Photosensitizers are special molecules which support these light-induced molecular transformations by electron or energy transfer using its abundant light absorbance and redox property [5]. Aldehydes are subjected to VLPC conditions either protected as acetals or directly during the course of a reaction [6]. Further transformations such as oxidation to COOH are also essential reaction of aldehydes [7]. Aldol condensations and enamines are further variations in their reactions as building blocks in organic synthesis [4]. Thus, the application of aldehydes as building blocks is now elaborated with their VLPC reactions adding to its reaction repertoire. In this chapter we will discuss on the recent developments on VLPC of aldehydes.
VLPC is advantageous over the conventional catalysis since it employs the clean, renewable, and readily available visible light from our sun and this state-of-the-art protocol is convenient in its operation. Bench chemists are fascinated by VLPC due to the ease of recycling the heterogeneous catalytic material by simple filtration and because reactions are carried at ambient temperature and the work-up procedure is quite simple. Eventually, this field and phenomenon of synthetic organic chemistry have emerged as an innovative subdiscipline over the last decade; the scientists have made a step forward by carrying out the asymmetric induction [8]; with the advancement in modern analytical tools and the hard work of enthusiastic chemists, VLPC of aldehydes is emerging exponentially.
In the visible-light photocatalysis, the catalytic species is activated by the action of light, and the photocatalytic material is mostly a semiconducting material which in turn is capable of activating even the small molecules [5]. When the catalytic material is irradiated with light, it undergoes the absorption of photon, and the electron (e−) is excited from the valence bond to the conduction band; consequently, a positive electron hole is generated in the semiconducting material (h+), and this process is termed as
Photosensitizers: [Ru(bpy)3]2+, [Ru(bpz)3]2+, fac-[Ir(ppy)3], [Ir(ppy)2(dtbbpy)]+. Properties of [Ru(bpy)3]2+ photocatalyst—[MLCT − λ = 452 nm].
Ru redox cycle: A—sacrificial electron acceptor; D—sacrificial electron donor; S—substrate; bpy—2,2′-bipyridine; MLCT (metal to ligand charge transfer) − λ = 452 nm.
The polypyridyl complexes of Ru and Ir afford unique chemical reactivities due to their long-lived excited states when excited by visible light [5]. They are chemically robust and possess redox properties that are further fine-tunable by modifying the polypyridyl ancillary ligands. The Ru(bpy)3Cl2 is a widely known and commonly used photoredox molecule. The absorption of visible light leads to excited states that can function both as oxidants and reductants, which allows the generation of radical cations or radical anions under mild conditions. The amphoteric redox reactivity of the excited triplet state of RuII(bpy)32+, (*RuII(bpy)3)2+, enables two distinct catalytic cycles, namely, the reductive quenching (RQC) and the oxidative quenching cycles (OQC). In RQC, (*RuII(bpy)3)2+ first oxidizes a reductant into a radical cation and reduces into RuI(bpy)3+ which subsequently reduces an oxidant into a radical anion species and converts itself into the ground-state catalyst. OQC starts with the oxidation of the complex (*RuII(bpy)3)2+ to RuIII(bpy)33+ followed by its reduction into RuII(bpy)32+.
Based on these viewpoints, cyclometallated Ir complexes have been rapidly developed due to their superior photophysical and photochemical properties. These photocatalysts are chemically robust and possess long-lived excited states. Their favorable redox properties allow redox-neutral reactions to be carried out as both reductants and oxidants that can be transiently generated during different stages in the catalytic process. This reactivity pattern thus is beneficial allowing exploration of alternate reaction pathways under benign reaction conditions. They have thus been used as photoredox catalysts and serve as photosensitizers in organic synthesis [5].
Aldehydes are prone to oxidation and amenable to attack by nucleophiles and can enolize, and as a result the ▬CHO functional group needs to be protected while carrying out the complex molecular architecture. Protection, de-protection, and reversing the reactivity or polarity through umpolung are the rudimentary strategies in the realm of organic synthesis. For these important tactics, recently VLPC has contributed a protection methodology, and the authors have protected the ▬CHO group as acetal [6]. The advantage of this protocol is that it does not employ the strong mineral, Lewis, and other acidic conditions; consequently the VLPC strategy presented by the chemists ranks as green technology. The protection was carried out using an organic dye, Eosin Y, with the use of [light-emitting diode (LED)] irradiation to promote the reaction under a milder condition. Several aldehydes were catalyzed in very high yields under household irradiation to the corresponding acetals (Figure 3).
Photocatalytic synthesis of acetals from aldehydes.
The oxidation of organic compounds is being continuously explored since it is an important functional group modification, and the bench chemists are looking for environmental compatible and cost-effective methodologies for the same. By means of commercially affordable catalytic materials, several aldehydes were conveniently converted into their respective carboxylic acids where the 1[O2] is used as oxidant catalyzed by Ru and Ir catalytic materials. The reaction is notably chemoselective and does not distress other oxidizable functional groups assembled within the molecule. Among the photosensitizers studied, Ir(dFppy)3 was the most efficient giving 99% yield of product from p-anisaldehyde. A wide range of aldehydes was studied with this catalyst and efficaciously oxidized under visible light [7] (Figure 4).
Photocatalytic oxidation of aldehydes [
Direct and catalytic C▬H activation or functionalization comprising of arylation, alkenylation, alkylation, allylation, and annulation reaction is an important field in the synthetic organic chemistry in the manufacture and the process development of pharmacologically and biologically active ingredients. Knowing the importance of C▬H activation, direct arylation of aldehydes has been achieved in a synergistic manner, where nickel catalyst was employed in combination with VLPC system. In this outstanding redox system, a hydrogen atom transfer (HAT) was achieved on the reactions in between commercially available aldehydes and aryl and alkyl bromides under milder conditions; it is interesting to note that the yields are excellent [9] (Figure 5).
Direct C▬H arylation and alkylation of aldehydes [
The mechanism is based on the photoexcitation of the Ir photocatalyst which gives rise to the highly oxidizing species Ir* Ir[dF(CF3)ppy]2(dtbbpy) which oxidizes quinuclidine to form a cation radical. This radical cation then engages in a HAT event with any aldehyde to generate the acyl radical. Simultaneously oxidative addition of aryl bromide to LnNi (0) generates the aryl-Ni (II) species which is intercepted by the acyl radical to form the acyl-Ni complex. Both the Ni and the Ir photoredox catalysts then turn over in a critical reductive elimination step to the desired ketone product while regenerating the Ir and Ni catalysts. It is interesting to note that using this protocol, a pharmacologically active ingredient, namely, haloperidol, a typical antipsychotic drug, was synthesized [9] (Figure 6).
Synthesis of haloperidol.
A two-step synthesis of haloperidol was achieved by this photoredox methodology. 1,4-Chlorobutanal was merged with 1-bromo-4-fluorobenzene using the photoredox protocol to yield the ketone in high yield. Further exposure of this to the piperidine nucleophile thus gave haloperidol in short steps.
The α-alkylation of carbonyl compounds is a routine affair for synthetic chemists both for making substituents and also to synthesize pharmaceutically active ingredients (Figures 7 and 8). In the case of α-alkylation of aldehydes, the acidic methylenic (CH2) hydrogen atoms are acidic in nature, and they can be removed; as a result an enol form is produced which directs the alkylating agents attached to the α-alkylation. A skillful execution of three catalytic materials together in a synergistic fashion enables an enantiomeric α-alkylation of aldehydes; mechanistically, the triple catalytic process is sequenced to deliver a hydrogen atom transfer, electron borrowing tendency, and chirality induction through chiral imidazolidinones or prolinols with a thiophenol where the iridium catalyst transfers the activation of molecules by means of light energy (λ). The α-alkylation is carried out both by inter- and intramolecularly where the alkenes are alkylated at the α-position to the aldehyde functional group to furnish cyclic and acyclic products. The process is atom economical with a stereoselective process, allowing the production of value-added molecules from feedstock chemicals in a single step while consuming only one photon [10].
Intermolecular alkylation with alkenes.
Intramolecular alkylation.
The mechanistic pathway is based on the excitation of Ir complex, and simultaneously the chiral reagent adds to the aldehyde compound through elimination of water and forms an enamine. The excited iridium complex oxidizes the enamine present in the reaction medium through a single-electron transfer mechanism; thus formed enaminyl radical adds to the alkene substrate producing a carbon radical which is finally trapped by the hydrogen atom transfer catalyst. During the work-up procedure, the iminium ion is hydrolyzed to get the enantiomerically enriched product, and the organocatalyst is regenerated. Finally the reduction of the thiyl radical by the Ir(I) species regenerates the thiol catalyst as well as the Ir(III) catalyst to complete the redox cycle.
With the success in the α-alkylation protocol, its intramolecular version also achieved where an intramolecular cyclization with tethered alkenes was first attempted to determine the feasibility of enantioselective ring formation reaction. Interestingly, carbocycles and heterocycles were synthesized with high yield and enantiocontrol. Tosamide- or carbamate-protected N-tethered aldehydic alkenes gave rise to the corresponding piperidines, ether-linked systems provided trans-substituted tetrahydropyrans, and carbocycles were also attained. Pyrrolidines were also formed as well as seven-membered rings such as azepanes or cycloheptanes. High stereocontrol was obtained with trisubstituted alkenes, and where multiple alkenes were available, only proximal alkenes reacted to provide the corresponding cyclic molecule.
Following this successful reaction, intermolecular reactions with styrene was attempted. A variety of substituted aldehydes provided the alkylated products in high yields and selectivity. Terminal alkenes were suitable substrates though 1,1-disubstituted alkenes reacted with moderate efficiency.
The fluorinated hydrocarbons possess unique physical properties and are so useful in dyes, polymers, agrochemicals, and drugs. In pharmaceuticals the perfluoroalkylated compounds which impart valuable physiological properties that enhance binding properties elevate lipophilicity and/or improved metabolic stability. The enantioselective incorporation of the CF3 and perfluoroalkyl groups has thus been a challenging task for the synthetic chemists, and the enantioselective α-alkyl trifluoromethylation of ketones and aldehydes has been elusive. First the enantioselective and organocatalytic α-trifluoromethylation and α-perfluoroalkylation of aldehydes have been successfully achieved using a commercially available iridium photocatalyst and imidazolidinone catalyst. MacMillan et al. describe the enantioselective trifluoromethylation of aldehydes via the successful merger of enamine and photoredox catalysis [11]. Their reaction is based on the property of electrophilic radicals to combine with facially biased enamine intermediates (derived from aldehydes and chiral amines). The radicals are derived from the reduction of alkyl halides by a photoredox catalyst (Ir(ppy)2(dtbbpy)). A broad range of perfluoroalkyl halides were found to participate in the enantioselective alkylation reaction. N-perfluoroalkyl substrates of varying chain length undergo successfully reductive radical formation and enamine addition with high yields and enantioselectivity (Figure 9).
α-Trifluoromethylation of aldehydes [
The α-alkylation of carbonyl compounds is always an essential tool in the synthetic organic chemistry. It can be carried out both inter- and intramolecularly; the intramolecular version builds up the cyclic compounds with enhanced stereoselectivity. Among the α-alkylation reactions, of late, α-trifluoromethylation reactions are being much exploited since these compounds are of greater importance in agrochemical and pharmaceutical compounds. Iodotrifluoromethane is employed as a trifluoromethylating agent under a VLPC condition where the reaction and optical yields are highly appreciable. Mechanistically, the light excites the Ir complex, which oxidizes the enamine compound through a single-electron transfer mechanism; the enamine radical adds with the alkene substrate producing carbon-centered radical; thus series of reaction provides the desired compound, and the catalyst is regenerated [12].
Photoredox catalysis and organocatalysis are two powerful fields of molecule activation that have found widespread application in the areas of inorganic coordination and organic chemistry. The merger of these two fields is an important solution in asymmetric chemical synthesis. Specifically, the enantioselective intermolecular α-alkylation of aldehydes with α-bromocarbonyls has been accomplished using an activation pathway that combines both the photoredox catalyst Ru(bpy)3Cl2 (where bpy is 2,2′-bipyridine) and an imidazolidinone organocatalyst. This simple alkylation reaction, which was previously elusive, is now broadly applicable and highly enantioselective [11].
The initiation of the reaction requires quenching of the photocatalyst excited state *Ru(bpy)32+ by a sacrificial amount of enamine to provide the strongly reducing Ru(bpy)3+. Electron transfer to the alkyl bromide induces fragmentation, affording bromide and the electron-deficient radical. Condensation of the aldehyde with the imidazolidinone organocatalyst furnishes chiral enamine. The C▬C bond formation then occurs by the radical electrophile addition to the accessible
The direct asymmetric alkylation of aldehydes.
Catalytic cycle—the direct asymmetric alkylation of aldehyde.
The synthetic design and developing methodology on the creation of C▬N bonds within the complex molecular architecture in a stereospecific manner is a challenging task which is routinely needed in the process development of drug molecules. Consequently, α-amino aldehydes are the valuable structural motifs in the process development of drug molecules. However, asymmetric α-amination of aldehydes poses a plethora of potential challenges since the reaction medium contains reagents and chemicals that can racemize product molecule. In this context, a VLPC methodology has been demonstrated for α-amination of aldehydes in an enantioselective fashion using nitrogen-centered radicals which enables the synthesis stable to racemization, a tactful synthetic methodology. N-centered radicals are easily generated using dinitrosulfonyloxy groups (ODNs) which are capable of producing the requisite heteroatom-centered radical upon exposure to household light and in the presence of designed catalyst. The nitrogen-centered radical thus is produced when treated with a transient π-rich enamine (derived from the coupling of an imidazolidinone catalyst with the aldehyde); upon photonic excitation, single-electron transfer reaction produces nitrogen-centered radical. Then the reaction proceeds to yield an iminium ion, which up on hydrolysis gives rise to enantiomerically enriched α-amino aldehyde [13] (Figures 12 and 13).
α-Amination of aldehydes.
Catalytic cycle of α-amination.
This is an organocatalytic and photoredox-based approach to the asymmetric α-amination of aldehyde, where a functionalized nitrogen is directly coupled with a formyl precursor. This protocol provides a ready access to N-substituted α-amino aldehyde architecture without any racemization with more than 85% enantiomeric excess.
The α- and γ-alkylations of aldehydes and enals, respectively, are an important C▬C bond forming reaction and very important in the building complex molecular architecture. These alkylations were reported as a photo-organocatalytic reaction where the product is enantioselective. The procedure is executed utilizing the commercially available aminocatalyst and carried out under the illumination of fluorescent light bulb in the absence of photoredox catalyst. The authors have demonstrated a strategy in which photochemical activation of substrates provides reactive radical species by the action of visible-light active photoredox catalyst. In this system the catalyst is chiral that acts as a dual catalytic system and provides an easy access to chiral molecules as products in an asymmetric fashion. In a sense, in the reaction medium, the transiently generated enamines undergo electronic excitation by the action of light form reactive radical species from organic halides, which, in turn, provide an effective stereochemical induction to yield enantioselective alkylated products [14] (Figures 14 and 15).
α-Alkylation of aldehydes.
γ-Alkylation of enals.
Aldehydes under the treatment with visible light underwent catalytic asymmetric cross-dehydrogenative coupling reactions with xanthenes and thioxanthenes, and it is interesting to note that xanthenes are important candidates in the dye stuff and drug industries. The coupling reactions are very highly enantioselective with good reaction and optical yields, and it was found to tolerate many functional groups under the reaction conditions that are described by the authors. They report that they were successful in their initial attempt itself on the symmetric cross-dehydrogenative coupling reaction between xanthene and pentanal employing Jørgensen’s catalyst. With this protocol they developed the scope of enantioselective CDC of xanthenes with various aldehydes. Excellent product and optical yields were obtained with aliphatic aldehydes, while sterically hindered isobutyraldehyde gave poor yield but with excellent optical yield. Thioxanthenes too are tolerant under CDC reaction conditions [15] (Figure 16).
Photoredox cross-dehydrogenative coupling of aldehydes with xanthenes.
The α-arylation of aldehyde-derived N,N-dialkylhydrazones with electron-deficient aryl and heteroaryl cyanides gives rise to substituted products under visible-light conditions with the use of photoredox catalysts. These structural motifs hold interesting pharmacological activities, and by these novel technologies, α,α′-diaryl-N,N-cycloalkylhydrazones were obtained in moderate yields, and it is to be noted that conventional methods for the same are found to be non-cost-effective and time-consuming in nature. In this typical methodology, hydrazine and aryl or heteroaryl cyanides were subjected to 455 nm blue light-emitting diodes with 1 mol% of Ir(ppy)3 as photocatalyst at 40°C with LiOAc (2 equiv) as base and DMSO as solvent to get the desired product [16] (Figure 17).
α-Arylation of hydrazones.
The mechanism describes that single-electron transfer occurs from Ir(III) to cyanoarene, then the oxidized Ir(IV) undergoes a second electron transfer mechanism with hydrazine forming a radical cation, and the Ir is ready for the catalytic cycle. LiOAc deprotonates the proton from hydrazine system; then various steps of reactions yield the product. Ultimately, structurally complex α,α′-diaryl-N,N-cycloalkylhydrazones were obtained in moderate yields by the repetition of the direct arylation protocol. A continuous flow procedure for the preparation of α-aryl-N,N-dialkylhydrazones on a multigram scale has also been established.
Realizing the importance of asymmetric synthesis of the late chemists, they are making use of photoredox and organocatalysis together, among which C▬C bond forming reactions are very important in the construction of biologically active compounds in a stereoselective fashion. One of the C▬C bond forming reactions which enable the alkylation of aldehydes with a reserved cyanide functional group in the new bond is useful for synthetic manipulations. The research article presented describes the generation of C▬C bond by making use of α-bromocyanoalkylated compounds as reagents, and this reaction generated β-cyano alkyls in a single synthetic operation with stereoselectivity. In a typical experimental procedure, an aldehydic compound α-bromoacetonitrile, Ru(bpy)3Cl2, asymmetric organocatalyst, and an imidazolidinone catalyst reaction mixture is irradiated by a 26 W CFL light source. The results are highly appreciable with preparative yield and with excellent enantioselectivity. More interestingly, this useful methodology has also demonstrated a total synthesis of a lignin natural product, namely, (−) bursehernin [17].
Piperazines are important class of compounds with important pharmacological properties such as anthelmintic, antiallergic, antibacterial, antihistaminic, antiemetic, and antimigrainic activities, and hence developing a working technology for the syntheses of piperazine analogues is very important to arrive at structural activity relationship. To arrive at an array of piperazines, recently a research article is reported that utilizes silicon-based reagents, and they denote this as silicon amine protocol (SLAP); in this process a variety of aromatic, heteroaromatic, and aliphatic aldehydes and ketones were employed to produce an array of piperazines using iridium-based photoredox catalyst (Ir[(ppy)2dtbbpy]PF6) and blue light radiation. The products obtained do not have any trace metal impurities since this protocol is tin-free alternative (SnAP—tin amine protocol). The reaction conditions enforced is mild and tolerates unprotected functional groups and steric hindrance and very importantly provides an access to wide array of piperazines without any trace metals for the SAR studies [18].
The direct β-functionalization of carbonyl groups is very little known. MacMillan et al. first reported the combination of organocatalysis and photoredox catalysis for the direct β-C▬H arylation of carbonyl compounds using benzonitrile as aryl donor (Figure 18). The proposed mechanistic rationale is shown in Figure 19 and follows an oxidative quenching cycle pathway, starting with the formation of a cyclohexadienyl radical anion [19].
β-Arylation of aldehydes.
β-Arylation of aldehydes—organocatalytic cycle.
Saturated aldehydes can be alkylated at the beta position directly by a synergistic combination of photoredox catalysis and organocatalysis [20]. Enamine oxidation by visible-light LED provides an activated β-enaminyl radical which readily combines with a wide range of Michael acceptors to produce β-alkyl aldehydes efficiently. Both inter- and intramolecular C▬H functionalizations are possible in an atom economical redox-neutral process (Figure 20).
Direct β-alkylation of enamines.
1,4-Diazabicyclo[2.2.2]octane (DABCO) as an organic base and DME as solvent were essential for the desired bond formation reaction. Thus a unique 5-πe-carbonyl activation utilizing the synergistic merger of organocatalysis and photoredox catalysis was used to accomplish the direct β-arylation of saturated ketones and aldehydes. A catalytically generated enaminyl radical formed via oxidation and β-deprotonation of an enamine and a radical anion generated by photocatalytic reduction of cyanoarene couple to form the β-carbonyl products. The generality of the activation platform was further demonstrated by a β-aldol reaction of ketones with transiently generated aryl ketyl radicals to form γ-hydroxy ketone adducts. The reaction was then further extended to intramolecular cyclization via formation of cyclic molecules through both 6-exo and 5-exo cyclizations with useful efficiencies and diastereocontrol. This proves further that the critical step does not involve radical-radical coupling (Figure 21).
5πe− activation, 6-exo to 5-exo.
Chiral iminium ion photochemistry is an emerging synthetic field; with the creativity of synthetic chemistry, they utilized [2+2] photocycloaddition to arrive at complex molecular architecture. In order to execute the [2+2] photocycloaddition, they have first synthesized an alkene tethered to a chiral iminium perchlorate salt, to procure the chiral product; the iminium salt is produced using a C2-symmetric chiral auxiliary. The bench chemists observed that (i) substituents at positions C2 and C5 of the pyrrolidine were crucial, (ii) the reaction process proceeds through single-electron transfer, (iii) the reaction takes place at the singlet hypersurface, (iv) this notable [2+2] cycloaddition reaction takes place via a concerted pathway resulting from the strong π to π* absorption, and (v) the iminium salt absorbs light at 280 nm. The reward from this developed protocol was 82% ee and 40% chemical yield [21] (Figure 22).
Iminium catalysis: [2+2] photocycloaddition reaction of iminium salts.
The chemistry of ortho-quinodimethanes is very well exploited for the generation of six-membered carbocyclic frameworks by reacting with a diene and through an inter- or intramolecular [4+2] cycloaddition. Under VLPC condition, reports indicate that the photoexcitation of ortho-alkyl-substituted benzaldehydes and benzophenones generates the ortho-quinodimethanes, a diene intermediate, whereas instead of undergoing the [4+2] cycloaddition to yield the carbocyclic product, it gave solely the β-benzylated products through a Michael-type addition reaction. The secondary amine employed in this reaction is solely responsible for the Michael-type product (Figure 23).
β-Benzylation of enals and enones.
The reaction mechanism is very interesting for the academic enthusiastic personalities; the chiral secondary amines react with the α,β-unsaturated compound that is used in the reaction medium. When the reaction mixture was irradiated with λ = 365 nm, the photons enolize the ortho-alkyl-substituted benzaldehyde or benzophenone to (E)-enol and then the iminium salts in close proximity with the other reactants to deliver the Michael-type addition products rather than [4+2] cycloadducts. A density functional theory (DFT) computational study was carried out by the authors to shed some light on this unusual reactivity, and the results indicated that this transformation proceeds through a water-assisted proton shuttle mechanism. The optical yields are excellent, and it is worth mentioning that no photocatalyst was needed in this reaction.
A major breakthrough in the field of asymmetric radical chemistry was represented by Melchiorre group; they achieved the first enantioselective radical conjugate addition (RCA) to β,β-disubstituted cyclic enones by a combination of photoredox catalysis and iminium-based organocatalysis. The organocatalyst and the primary amine moiety react with a α,β-unsaturated enone forming a chiral iminium ion as the reactive intermediate; the 1,3-benzodioxole present in the reaction medium upon irradiation by means of an UV light-emitting diode and in the presence of tetrabutylammonium decatungstate (TBADT) generates a carbon-centered radical. Thus generated carbon-centered radical being short-lived and active, it reacts with the chiral iminium ion producing an α-iminyl radical cation. Then through an intramolecular SET process, the α-iminyl radical cation was reduced to enamine. A tautomerism reaction, that is, enamine-imine tautomerization, regenerates photocatalyst TBADT, and finally the work procedure gives rise to the product with excellent enantio- and diastereoselectivities, and the chiral amine is recovered [22] (Figure 24).
Iminium catalysis: β-alkylation of enals and enones.
Following the footpaths of iminium catalysis, the twin brothers, namely, the photoredox catalysis and organocatalysis, fruitfully accomplished the enantioselective α-alkylation of aldehydes; the photoredox catalyst employed was 0.5 mol% of Ru(bpy)3Cl2 (bpy = 2,20-bipyridine), and the photocatalyst utilized was 20 mol% of a chiral imidazolidinone. Under the reaction condition, the substrate aldehydic compound reacts with a chiral enamine (organocatalyst) forming a chiral enamine intermediate; thereby the substrate is tuned to be nucleophilic in nature, and the nucleophilicity arises at the α-position to the aldehydic chromophore. Simultaneously, in the reaction medium, the photocatalyst is electronically excited by the visible light; once excited, it accepts a single electron from the chiral enamine, and the Ru [I] species then reduces the α-bromocarbonyl compound, and in this process the photocatalyst is regenerated. At the work-up the coupled product is released from the enamine with high stereoselectivity and in good yields (Figure 25).
Enamine catalysis.
α-Benzylation and α-alkylation are thematically one and the same; however, much recent advances in α-benzylation of carbonyl compounds were reported with stereoselectivity (Figure 26).
Enamine benzylation.
A variety of electron-deficient aryl and heteroaryl methylene bromides were examined as the benzylating agents, and they were coupled with a range of aldehydes bearing different functional groups efficiently with excellent enantioselectivity. The benzylation reaction proceeds via an oxidative quenching cycle, in contrast to the reductive quenching cycle operation in the α-alkylation reaction. The hybrid organocatalytic cycle and photoredox catalytic cycle are similar to the reaction of aldehydes with alkyl halides described in Figure 11. The Ir photocatalyst fac-Ir(ppy)3 and imidazolidinone organocatalyst generate the benzyl radical from electron-deficient benzyl halides. This benzyl radical then couples with the chiral enamine providing α-amino radical which is oxidized by the intermediate Ir(IV) species. Hydrolysis of the iminium ion releases the α-benzyl aldehyde. A range of electron-deficient heteroaromatics such as pyridines, pyrazines, pyrimidines, quinolines, and benzimidazoles undergo facile reaction (Figure 27).
A catalytic cycle—enantioselective benzylation of aldehydes.
The α-hydroxylation of carbonyl compounds is a very important class of reaction in the design of drug molecules; mostly the hydroxylation is appended in a stereoselective fashion. Conveniently it is achieved by enolizing the carbonyl, and the oxidation is done by oxidizing agents such as epoxides, OsO4, and so on. Rarely the singlet oxygen is used for this functional group introduction. In this VLPC condition, the hardships related to the α-hydroxylation reactions are tackled with ease; an amine-catalyzed enantioselective α-hydroxylation of aldehydes under photochemical condition was achieved where (L)-α-Me proline-based organocatalyst was exploited and singlet oxygen is employed instead of explosive oxidizing agents. Mechanistically the amino acid-based organocatalyst activated the aldehyde, and the α-position is ready for reactivity. Photosensitizer tetraphenylporphyrin (TPP) sensitizes 3O2 to 1O2 by the action of visible light, which then reacts with the substrate enamine through an ene-type reaction, forming α-hydroperoxide which is then reduced using NaBH4 to get 1,2-diols. Later this methodology was extended to cyclic ketones and yielded appreciable enantioselectivity (Figure 28).
Enamine hydroxylation.
The α-functionalization of carbonyl compounds is easily carried out, whereas functionalizing at the β-position is not easy and requires multiple synthetic operations. With creativity and with clear understanding of radical chemistry using a VLPC protocol, these authors have enolized the cyclic ketones; thereby a double bond is formed, and the radical chemistry created an allyl radical at the β-position. In the reaction medium, the iridium-based catalyst generated arene radical cation from cyanoarenes, which reacts with the allyl radical and forms the β-substituted ketones with the elimination of the cyanide group from the arene (Figure 29).
Ketone β-arylation.
A relay visible-light photocatalysis strategy using formal 4+1 annulation and aromatization was achieved. Three successive photoredox cycles (one oxidative cycle and two reductive quenching cycles) were engaged in a reaction with one photocatalyst. Multiple quenching cycles could be demonstrated in a single reaction involving formal 4+1 annulation of hydrazone with 2-bromo diethylmalonate [23] (Figure 30).
Relay VLPC.
Photosynthesis has attracted biologists, physicists, and chemists for centuries; chemists by understanding how the plants synthesized chemicals using sunlight have been inspired, and that resulted in this new domain. Ultimately these new sets of reactions under VLPC are photosynthesis mimic reactions, and the chemists brought the process into action at the laboratories.
VLPC strategies developed by chemists in recent years portrait the esthetic taste and the design of energy-saving and environmentally compatible and benign features in this innovative domain of organic synthesis.
Among all the subdisciplines of catalysis, the newly emerged gifted child, namely, visible-light photoredox catalysis, has grown rapidly and has made a great of deal of interest in both academia and industry; in the near future, we will be witnessing the process development of drug molecules.
The twin catalysis comprising a chiral agent and the transition metal catalyst brought forward the asymmetric synthesis in a one-pot synthetic fashion in this neoteric protocol which portraits the highest level of creativity of synthetic chemists. Consequently, it can be construed that from the catalytic professionals, more VPLC protocols will emerge to attain pharmaceutically active ingredients through industrial manufacturing processes, especially in enantiomerically enriched forms.
In terms of kinetics, not much work is done, and such research articles are expected in the pipeline; much work has to be done on the recyclability and reusability of catalytic materials including the studies on leaching.
It is interesting to note that only in this domain the methodology quickly reached to the stage of asymmetric synthesis in a rapid way, implying the success in the process development of drug molecules; subsequently, more process developments are expected as the industrial process.
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Generally, the phytochemical constituents of plants fall into two categories based on their role in basic metabolic processes, namely primary and secondary metabolites. Primary plant metabolites are involved in basic life functions; therefore, they are more or less similar in all living cells. On the other hand, secondary plant metabolites are products of subsidiary pathways as the shikimic acid pathway. In the course of studying, the medicinal effect of herbals is oriented towards the secondary plant metabolites. Secondary plant metabolites played an important role in alleviating several aliments in the traditional medicine and folk uses. In modern medicine, they provided lead compounds for the production of medications for treating various diseases from migraine up to cancer. Secondary plant metabolites are classified according to their chemical structures into various classes. In this chapter, we will be presenting various classes of secondary plant metabolites, their distribution in different plant families and their important medicinal uses.",book:{id:"6302",slug:"herbal-medicine",title:"Herbal Medicine",fullTitle:"Herbal Medicine"},signatures:"Rehab A. Hussein and Amira A. El-Anssary",authors:[{id:"212117",title:"Dr.",name:"Rehab",middleName:null,surname:"Hussein",slug:"rehab-hussein",fullName:"Rehab Hussein"},{id:"221140",title:"Dr.",name:"Amira",middleName:null,surname:"El-Anssary",slug:"amira-el-anssary",fullName:"Amira El-Anssary"}]},{id:"64851",doi:"10.5772/intechopen.80348",title:"Herbal Medicines in African Traditional Medicine",slug:"herbal-medicines-in-african-traditional-medicine",totalDownloads:14206,totalCrossrefCites:30,totalDimensionsCites:52,abstract:"African traditional medicine is a form of holistic health care system organized into three levels of specialty, namely divination, spiritualism, and herbalism. The traditional healer provides health care services based on culture, religious background, knowledge, attitudes, and beliefs that are prevalent in his community. Illness is regarded as having both natural and supernatural causes and thus must be treated by both physical and spiritual means, using divination, incantations, animal sacrifice, exorcism, and herbs. Herbal medicine is the cornerstone of traditional medicine but may include minerals and animal parts. The adjustment is ok, but may be replaced with –‘ Herbal medicine was once termed primitive by western medicine but through scientific investigations there is a better understanding of its therapeutic activities such that many pharmaceuticals have been modeled on phytochemicals derived from it. Major obstacles to the use of African medicinal plants are their poor quality control and safety. Traditional medical practices are still shrouded with much secrecy, with few reports or documentations of adverse reactions. However, the future of African traditional medicine is bright if viewed in the context of service provision, increase of health care coverage, economic potential, and poverty reduction. Formal recognition and integration of traditional medicine into conventional medicine will hold much promise for the future.",book:{id:"6302",slug:"herbal-medicine",title:"Herbal Medicine",fullTitle:"Herbal Medicine"},signatures:"Ezekwesili-Ofili Josephine Ozioma and Okaka Antoinette Nwamaka\nChinwe",authors:[{id:"191264",title:"Prof.",name:"Josephine",middleName:"Ozioma",surname:"Ezekwesili-Ofili",slug:"josephine-ezekwesili-ofili",fullName:"Josephine Ezekwesili-Ofili"},{id:"211585",title:"Prof.",name:"Antoinette",middleName:null,surname:"Okaka",slug:"antoinette-okaka",fullName:"Antoinette Okaka"}]},{id:"54028",doi:"10.5772/67291",title:"Chemical Composition and Biological Activities of Mentha Species",slug:"chemical-composition-and-biological-activities-of-mentha-species",totalDownloads:7474,totalCrossrefCites:13,totalDimensionsCites:46,abstract:"The genus Mentha L. (Lamiaceae) is distributed all over the world and can be found in many environments. Mentha species, one of the world’s oldest and most popular herbs, are widely used in cooking, in cosmetics, and as alternative or complementary therapy, mainly for the treatment of gastrointestinal disorders like flatulence, indigestion, nausea, vomiting, anorexia, and ulcerative colitis. Furthermore, it is well documented that the essential oil and extracts of Mentha species possess antimicrobial, fungicidal, antiviral, insecticidal, and antioxidant properties. The economic importance of mints is also evident; mint oil and its constituents and derivatives are used as flavoring agents throughout the world in food, pharmaceutical, herbal, perfumery, and flavoring industry. To provide a scientific basis for their traditional uses, several studies have been conducted to determine the chemical composition of mints and assess their biological activities. This chapter describes the therapeutic effects and uses of Mentha species and their constituents, particularly essential oils and phenolic compounds; some additional biological activities will also be considered.",book:{id:"5612",slug:"aromatic-and-medicinal-plants-back-to-nature",title:"Aromatic and Medicinal Plants",fullTitle:"Aromatic and Medicinal Plants - Back to Nature"},signatures:"Fatiha Brahmi, Madani Khodir, Chibane Mohamed and Duez Pierre",authors:[{id:"193281",title:"Dr.",name:"Fatiha",middleName:null,surname:"Brahmi",slug:"fatiha-brahmi",fullName:"Fatiha Brahmi"},{id:"199693",title:"Prof.",name:"Khodir",middleName:null,surname:"Madani",slug:"khodir-madani",fullName:"Khodir Madani"},{id:"199694",title:"Prof.",name:"Pierre",middleName:null,surname:"Duez",slug:"pierre-duez",fullName:"Pierre Duez"},{id:"203738",title:"Prof.",name:"Mohamed",middleName:null,surname:"Chibane",slug:"mohamed-chibane",fullName:"Mohamed Chibane"}]},{id:"58270",doi:"10.5772/intechopen.72437",title:"Toxicity and Safety Implications of Herbal Medicines Used in Africa",slug:"toxicity-and-safety-implications-of-herbal-medicines-used-in-africa",totalDownloads:3376,totalCrossrefCites:16,totalDimensionsCites:39,abstract:"The use of herbal medicines has seen a great upsurge globally. In developing countries, many patronize them largely due to cultural acceptability, availability and cost. In developed countries, they are used because they are natural and therefore assumed to be safer than allopathic medicines. In recent times, however, there has been a growing concern about their safety. This has created a situation of ambivalence in discussions regarding their use. Some medicinal plants are intrinsically toxic by virtue of their constituents and can cause adverse reactions if inappropriately used. Other factors such as herb-drug interactions, lack of adherence to good manufacturing practice (GMP), poor regulatory measures and adulteration may also lead to adverse events in their use. Many in vivo tests on aqueous extracts largely support the safety of herbal medicines, whereas most in vitro tests on isolated single cells mostly with extracts other than aqueous ones show contrary results and thus continue the debate on herbal medicine safety. It is expected that toxicity studies concerning herbal medicine should reflect their traditional use to allow for rational discussions regarding their safety for their beneficial use. While various attempts continue to establish the safety of various herbal medicines in man, their cautious and responsible use is required.",book:{id:"6302",slug:"herbal-medicine",title:"Herbal Medicine",fullTitle:"Herbal Medicine"},signatures:"Merlin L.K. Mensah, Gustav Komlaga, Arnold D. Forkuo, Caleb\nFirempong, Alexander K. Anning and Rita A. Dickson",authors:[{id:"190435",title:"Dr.",name:"Caleb",middleName:null,surname:"Firempong",slug:"caleb-firempong",fullName:"Caleb Firempong"},{id:"212111",title:"Dr.",name:"Gustav",middleName:null,surname:"Komlaga",slug:"gustav-komlaga",fullName:"Gustav Komlaga"},{id:"217045",title:"Dr.",name:"Arnold Forkuo",middleName:null,surname:"Donkor",slug:"arnold-forkuo-donkor",fullName:"Arnold Forkuo Donkor"},{id:"217049",title:"Prof.",name:"Merlin Lincoln Kwao",middleName:null,surname:"Mensah",slug:"merlin-lincoln-kwao-mensah",fullName:"Merlin Lincoln Kwao Mensah"},{id:"217488",title:"Dr.",name:"Alexander K.",middleName:null,surname:"Anning",slug:"alexander-k.-anning",fullName:"Alexander K. Anning"},{id:"223959",title:"Prof.",name:"Akosua Rita",middleName:null,surname:"Dickson",slug:"akosua-rita-dickson",fullName:"Akosua Rita Dickson"}]},{id:"26489",doi:"10.5772/28224",title:"Alternative and Traditional Medicines Systems in Pakistan: History, Regulation, Trends, Usefulness, Challenges, Prospects and Limitations",slug:"alternative-and-traditional-medicines-systems-in-pakistan-history-regulation-trends-usefulness-chall",totalDownloads:9199,totalCrossrefCites:9,totalDimensionsCites:21,abstract:null,book:{id:"542",slug:"a-compendium-of-essays-on-alternative-therapy",title:"A Compendium of Essays on Alternative Therapy",fullTitle:"A Compendium of Essays on Alternative Therapy"},signatures:"Shahzad Hussain, Farnaz Malik, Nadeem Khalid, Muhammad Abdul Qayyum and Humayun Riaz",authors:[{id:"73162",title:"Dr.",name:"Shahzad",middleName:null,surname:"Hussain",slug:"shahzad-hussain",fullName:"Shahzad Hussain"},{id:"82266",title:"Dr.",name:"Farnaz",middleName:null,surname:"Malik",slug:"farnaz-malik",fullName:"Farnaz Malik"},{id:"124185",title:"Dr.",name:"Humayun",middleName:null,surname:"Riaz",slug:"humayun-riaz",fullName:"Humayun Riaz"},{id:"124186",title:"Mr.",name:"Muhammad Abdul",middleName:null,surname:"Qayyum",slug:"muhammad-abdul-qayyum",fullName:"Muhammad Abdul Qayyum"},{id:"125340",title:"Mr.",name:"Nadeem",middleName:null,surname:"Khalid",slug:"nadeem-khalid",fullName:"Nadeem Khalid"}]}],mostDownloadedChaptersLast30Days:[{id:"64851",title:"Herbal Medicines in African Traditional Medicine",slug:"herbal-medicines-in-african-traditional-medicine",totalDownloads:14207,totalCrossrefCites:30,totalDimensionsCites:52,abstract:"African traditional medicine is a form of holistic health care system organized into three levels of specialty, namely divination, spiritualism, and herbalism. The traditional healer provides health care services based on culture, religious background, knowledge, attitudes, and beliefs that are prevalent in his community. Illness is regarded as having both natural and supernatural causes and thus must be treated by both physical and spiritual means, using divination, incantations, animal sacrifice, exorcism, and herbs. Herbal medicine is the cornerstone of traditional medicine but may include minerals and animal parts. The adjustment is ok, but may be replaced with –‘ Herbal medicine was once termed primitive by western medicine but through scientific investigations there is a better understanding of its therapeutic activities such that many pharmaceuticals have been modeled on phytochemicals derived from it. Major obstacles to the use of African medicinal plants are their poor quality control and safety. Traditional medical practices are still shrouded with much secrecy, with few reports or documentations of adverse reactions. However, the future of African traditional medicine is bright if viewed in the context of service provision, increase of health care coverage, economic potential, and poverty reduction. Formal recognition and integration of traditional medicine into conventional medicine will hold much promise for the future.",book:{id:"6302",slug:"herbal-medicine",title:"Herbal Medicine",fullTitle:"Herbal Medicine"},signatures:"Ezekwesili-Ofili Josephine Ozioma and Okaka Antoinette Nwamaka\nChinwe",authors:[{id:"191264",title:"Prof.",name:"Josephine",middleName:"Ozioma",surname:"Ezekwesili-Ofili",slug:"josephine-ezekwesili-ofili",fullName:"Josephine Ezekwesili-Ofili"},{id:"211585",title:"Prof.",name:"Antoinette",middleName:null,surname:"Okaka",slug:"antoinette-okaka",fullName:"Antoinette Okaka"}]},{id:"61866",title:"Plants Secondary Metabolites: The Key Drivers of the Pharmacological Actions of Medicinal Plants",slug:"plants-secondary-metabolites-the-key-drivers-of-the-pharmacological-actions-of-medicinal-plants",totalDownloads:8875,totalCrossrefCites:56,totalDimensionsCites:140,abstract:"The vast and versatile pharmacological effects of medicinal plants are basically dependent on their phytochemical constituents. Generally, the phytochemical constituents of plants fall into two categories based on their role in basic metabolic processes, namely primary and secondary metabolites. Primary plant metabolites are involved in basic life functions; therefore, they are more or less similar in all living cells. On the other hand, secondary plant metabolites are products of subsidiary pathways as the shikimic acid pathway. In the course of studying, the medicinal effect of herbals is oriented towards the secondary plant metabolites. Secondary plant metabolites played an important role in alleviating several aliments in the traditional medicine and folk uses. In modern medicine, they provided lead compounds for the production of medications for treating various diseases from migraine up to cancer. Secondary plant metabolites are classified according to their chemical structures into various classes. In this chapter, we will be presenting various classes of secondary plant metabolites, their distribution in different plant families and their important medicinal uses.",book:{id:"6302",slug:"herbal-medicine",title:"Herbal Medicine",fullTitle:"Herbal Medicine"},signatures:"Rehab A. Hussein and Amira A. El-Anssary",authors:[{id:"212117",title:"Dr.",name:"Rehab",middleName:null,surname:"Hussein",slug:"rehab-hussein",fullName:"Rehab Hussein"},{id:"221140",title:"Dr.",name:"Amira",middleName:null,surname:"El-Anssary",slug:"amira-el-anssary",fullName:"Amira El-Anssary"}]},{id:"77433",title:"Extraction of Bioactive Compounds from Medicinal Plants and Herbs",slug:"extraction-of-bioactive-compounds-from-medicinal-plants-and-herbs",totalDownloads:1266,totalCrossrefCites:2,totalDimensionsCites:5,abstract:"Human beings have relied on herbs and medicinal plants as sources of food and remedy from time immemorial. Bioactive compounds from plants are currently the subject of much research interest, but their extraction as part of phytochemical and/or biological investigations present specific challenges. Herbalists or scientists have developed many protocols of extraction of bioactive ingredients to ensure the effectiveness and the efficacy of crude drugs that were used to get relief from sickness. With the advent of new leads from plants such as morphine, quinine, taxol, artemisinin, and alkaloids from Voacanga species, a lot of attention is paid to the mode of extraction of active phytochemicals to limit the cost linked to the synthesis and isolation. Thus, the extraction of active compounds from plants needs appropriate extraction methods and techniques that provide bioactive ingredients-rich extracts and fractions. The extraction procedures, therefore, play a critical role in the yield, the nature of phytochemical content, etc. This chapter aims to present, describe, and compare extraction procedures of bioactive compounds from herbs and medicinal plants.",book:{id:"10356",slug:"natural-medicinal-plants",title:"Natural Medicinal Plants",fullTitle:"Natural Medicinal Plants"},signatures:"Fongang Fotsing Yannick Stéphane, Bankeu Kezetas Jean Jules, Gaber El-Saber Batiha, Iftikhar Ali and Lenta Ndjakou Bruno",authors:[{id:"224515",title:"Dr.",name:"Fongang Fotsing",middleName:null,surname:"Yannick Stéphane",slug:"fongang-fotsing-yannick-stephane",fullName:"Fongang Fotsing Yannick Stéphane"},{id:"227816",title:"Dr.",name:"Bankeu Kezetas",middleName:null,surname:"Jean Jules",slug:"bankeu-kezetas-jean-jules",fullName:"Bankeu Kezetas Jean Jules"},{id:"227817",title:"Prof.",name:"Lenta Ndjakou",middleName:null,surname:"Bruno",slug:"lenta-ndjakou-bruno",fullName:"Lenta Ndjakou Bruno"},{id:"349790",title:"Prof.",name:"Gaber",middleName:null,surname:"El-Saber Batiha",slug:"gaber-el-saber-batiha",fullName:"Gaber El-Saber Batiha"},{id:"357350",title:"Dr.",name:"Iftikhar",middleName:null,surname:"Ali",slug:"iftikhar-ali",fullName:"Iftikhar Ali"}]},{id:"26491",title:"Homeopathy: Treatment of Cancer with the Banerji Protocols",slug:"homeopathy-treatment-of-cancer-with-the-banerji-protocols",totalDownloads:54048,totalCrossrefCites:1,totalDimensionsCites:2,abstract:null,book:{id:"542",slug:"a-compendium-of-essays-on-alternative-therapy",title:"A Compendium of Essays on Alternative Therapy",fullTitle:"A Compendium of Essays on Alternative Therapy"},signatures:"Prasanta Banerji and Pratip Banerji",authors:[{id:"79939",title:"Dr",name:"Prasanta",middleName:null,surname:"Banerji",slug:"prasanta-banerji",fullName:"Prasanta Banerji"},{id:"79943",title:"Dr.",name:"Pratip",middleName:null,surname:"Banerji",slug:"pratip-banerji",fullName:"Pratip Banerji"}]},{id:"54028",title:"Chemical Composition and Biological Activities of Mentha Species",slug:"chemical-composition-and-biological-activities-of-mentha-species",totalDownloads:7474,totalCrossrefCites:13,totalDimensionsCites:46,abstract:"The genus Mentha L. (Lamiaceae) is distributed all over the world and can be found in many environments. Mentha species, one of the world’s oldest and most popular herbs, are widely used in cooking, in cosmetics, and as alternative or complementary therapy, mainly for the treatment of gastrointestinal disorders like flatulence, indigestion, nausea, vomiting, anorexia, and ulcerative colitis. Furthermore, it is well documented that the essential oil and extracts of Mentha species possess antimicrobial, fungicidal, antiviral, insecticidal, and antioxidant properties. The economic importance of mints is also evident; mint oil and its constituents and derivatives are used as flavoring agents throughout the world in food, pharmaceutical, herbal, perfumery, and flavoring industry. To provide a scientific basis for their traditional uses, several studies have been conducted to determine the chemical composition of mints and assess their biological activities. This chapter describes the therapeutic effects and uses of Mentha species and their constituents, particularly essential oils and phenolic compounds; some additional biological activities will also be considered.",book:{id:"5612",slug:"aromatic-and-medicinal-plants-back-to-nature",title:"Aromatic and Medicinal Plants",fullTitle:"Aromatic and Medicinal Plants - Back to Nature"},signatures:"Fatiha Brahmi, Madani Khodir, Chibane Mohamed and Duez Pierre",authors:[{id:"193281",title:"Dr.",name:"Fatiha",middleName:null,surname:"Brahmi",slug:"fatiha-brahmi",fullName:"Fatiha Brahmi"},{id:"199693",title:"Prof.",name:"Khodir",middleName:null,surname:"Madani",slug:"khodir-madani",fullName:"Khodir Madani"},{id:"199694",title:"Prof.",name:"Pierre",middleName:null,surname:"Duez",slug:"pierre-duez",fullName:"Pierre Duez"},{id:"203738",title:"Prof.",name:"Mohamed",middleName:null,surname:"Chibane",slug:"mohamed-chibane",fullName:"Mohamed Chibane"}]}],onlineFirstChaptersFilter:{topicId:"991",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:89,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:32,numberOfPublishedChapters:318,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:106,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:15,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"14",title:"Artificial Intelligence",doi:"10.5772/intechopen.79920",issn:"2633-1403",scope:"Artificial Intelligence (AI) is a rapidly developing multidisciplinary research area that aims to solve increasingly complex problems. In today's highly integrated world, AI promises to become a robust and powerful means for obtaining solutions to previously unsolvable problems. This Series is intended for researchers and students alike interested in this fascinating field and its many applications.",coverUrl:"https://cdn.intechopen.com/series/covers/14.jpg",latestPublicationDate:"June 11th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:9,editor:{id:"218714",title:"Prof.",name:"Andries",middleName:null,surname:"Engelbrecht",slug:"andries-engelbrecht",fullName:"Andries Engelbrecht",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRNR8QAO/Profile_Picture_1622640468300",biography:"Andries Engelbrecht received the Masters and PhD degrees in Computer Science from the University of Stellenbosch, South Africa, in 1994 and 1999 respectively. He is currently appointed as the Voigt Chair in Data Science in the Department of Industrial Engineering, with a joint appointment as Professor in the Computer Science Division, Stellenbosch University. Prior to his appointment at Stellenbosch University, he has been at the University of Pretoria, Department of Computer Science (1998-2018), where he was appointed as South Africa Research Chair in Artifical Intelligence (2007-2018), the head of the Department of Computer Science (2008-2017), and Director of the Institute for Big Data and Data Science (2017-2018). In addition to a number of research articles, he has written two books, Computational Intelligence: An Introduction and Fundamentals of Computational Swarm Intelligence.",institutionString:null,institution:{name:"Stellenbosch University",institutionURL:null,country:{name:"South Africa"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:6,paginationItems:[{id:"22",title:"Applied Intelligence",coverUrl:"https://cdn.intechopen.com/series_topics/covers/22.jpg",isOpenForSubmission:!0,editor:{id:"27170",title:"Prof.",name:"Carlos",middleName:"M.",surname:"Travieso-Gonzalez",slug:"carlos-travieso-gonzalez",fullName:"Carlos Travieso-Gonzalez",profilePictureURL:"https://mts.intechopen.com/storage/users/27170/images/system/27170.jpeg",biography:"Carlos M. Travieso-González received his MSc degree in Telecommunication Engineering at Polytechnic University of Catalonia (UPC), Spain in 1997, and his Ph.D. degree in 2002 at the University of Las Palmas de Gran Canaria (ULPGC-Spain). He is a full professor of signal processing and pattern recognition and is head of the Signals and Communications Department at ULPGC, teaching from 2001 on subjects on signal processing and learning theory. His research lines are biometrics, biomedical signals and images, data mining, classification system, signal and image processing, machine learning, and environmental intelligence. He has researched in 52 international and Spanish research projects, some of them as head researcher. He is co-author of 4 books, co-editor of 27 proceedings books, guest editor for 8 JCR-ISI international journals, and up to 24 book chapters. He has over 450 papers published in international journals and conferences (81 of them indexed on JCR – ISI - Web of Science). He has published seven patents in the Spanish Patent and Trademark Office. He has been a supervisor on 8 Ph.D. theses (11 more are under supervision), and 130 master theses. He is the founder of The IEEE IWOBI conference series and the president of its Steering Committee, as well as the founder of both the InnoEducaTIC and APPIS conference series. He is an evaluator of project proposals for the European Union (H2020), Medical Research Council (MRC, UK), Spanish Government (ANECA, Spain), Research National Agency (ANR, France), DAAD (Germany), Argentinian Government, and the Colombian Institutions. He has been a reviewer in different indexed international journals (<70) and conferences (<250) since 2001. He has been a member of the IASTED Technical Committee on Image Processing from 2007 and a member of the IASTED Technical Committee on Artificial Intelligence and Expert Systems from 2011. \n\nHe has held the general chair position for the following: ACM-APPIS (2020, 2021), IEEE-IWOBI (2019, 2020 and 2020), A PPIS (2018, 2019), IEEE-IWOBI (2014, 2015, 2017, 2018), InnoEducaTIC (2014, 2017), IEEE-INES (2013), NoLISP (2011), JRBP (2012), and IEEE-ICCST (2005)\n\nHe is an associate editor of the Computational Intelligence and Neuroscience Journal (Hindawi – Q2 JCR-ISI). He was vice dean from 2004 to 2010 in the Higher Technical School of Telecommunication Engineers at ULPGC and the vice dean of Graduate and Postgraduate Studies from March 2013 to November 2017. He won the “Catedra Telefonica” Awards in Modality of Knowledge Transfer, 2017, 2018, and 2019 editions, and awards in Modality of COVID Research in 2020.\n\nPublic References:\nResearcher ID http://www.researcherid.com/rid/N-5967-2014\nORCID https://orcid.org/0000-0002-4621-2768 \nScopus Author ID https://www.scopus.com/authid/detail.uri?authorId=6602376272\nScholar Google https://scholar.google.es/citations?user=G1ks9nIAAAAJ&hl=en \nResearchGate https://www.researchgate.net/profile/Carlos_Travieso",institutionString:null,institution:{name:"University of Las Palmas de Gran Canaria",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"23",title:"Computational Neuroscience",coverUrl:"https://cdn.intechopen.com/series_topics/covers/23.jpg",isOpenForSubmission:!0,editor:{id:"14004",title:"Dr.",name:"Magnus",middleName:null,surname:"Johnsson",slug:"magnus-johnsson",fullName:"Magnus Johnsson",profilePictureURL:"https://mts.intechopen.com/storage/users/14004/images/system/14004.png",biography:"Dr Magnus Johnsson is a cross-disciplinary scientist, lecturer, scientific editor and AI/machine learning consultant from Sweden. \n\nHe is currently at Malmö University in Sweden, but also held positions at Lund University in Sweden and at Moscow Engineering Physics Institute. \nHe holds editorial positions at several international scientific journals and has served as a scientific editor for books and special journal issues. \nHis research interests are wide and include, but are not limited to, autonomous systems, computer modeling, artificial neural networks, artificial intelligence, cognitive neuroscience, cognitive robotics, cognitive architectures, cognitive aids and the philosophy of mind. \n\nDr. Johnsson has experience from working in the industry and he has a keen interest in the application of neural networks and artificial intelligence to fields like industry, finance, and medicine. \n\nWeb page: www.magnusjohnsson.se",institutionString:null,institution:{name:"Malmö University",institutionURL:null,country:{name:"Sweden"}}},editorTwo:null,editorThree:null},{id:"24",title:"Computer Vision",coverUrl:"https://cdn.intechopen.com/series_topics/covers/24.jpg",isOpenForSubmission:!0,editor:{id:"294154",title:"Prof.",name:"George",middleName:null,surname:"Papakostas",slug:"george-papakostas",fullName:"George Papakostas",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002hYaGbQAK/Profile_Picture_1624519712088",biography:"George A. Papakostas has received a diploma in Electrical and Computer Engineering in 1999 and the M.Sc. and Ph.D. degrees in Electrical and Computer Engineering in 2002 and 2007, respectively, from the Democritus University of Thrace (DUTH), Greece. Dr. Papakostas serves as a Tenured Full Professor at the Department of Computer Science, International Hellenic University, Greece. Dr. Papakostas has 10 years of experience in large-scale systems design as a senior software engineer and technical manager, and 20 years of research experience in the field of Artificial Intelligence. Currently, he is the Head of the “Visual Computing” division of HUman-MAchines INteraction Laboratory (HUMAIN-Lab) and the Director of the MPhil program “Advanced Technologies in Informatics and Computers” hosted by the Department of Computer Science, International Hellenic University. He has (co)authored more than 150 publications in indexed journals, international conferences and book chapters, 1 book (in Greek), 3 edited books, and 5 journal special issues. His publications have more than 2100 citations with h-index 27 (GoogleScholar). His research interests include computer/machine vision, machine learning, pattern recognition, computational intelligence. \nDr. Papakostas served as a reviewer in numerous journals, as a program\ncommittee member in international conferences and he is a member of the IAENG, MIR Labs, EUCogIII, INSTICC and the Technical Chamber of Greece (TEE).",institutionString:null,institution:{name:"International Hellenic University",institutionURL:null,country:{name:"Greece"}}},editorTwo:null,editorThree:null},{id:"25",title:"Evolutionary Computation",coverUrl:"https://cdn.intechopen.com/series_topics/covers/25.jpg",isOpenForSubmission:!0,editor:{id:"136112",title:"Dr.",name:"Sebastian",middleName:null,surname:"Ventura Soto",slug:"sebastian-ventura-soto",fullName:"Sebastian Ventura Soto",profilePictureURL:"https://mts.intechopen.com/storage/users/136112/images/system/136112.png",biography:"Sebastian Ventura is a Spanish researcher, a full professor with the Department of Computer Science and Numerical Analysis, University of Córdoba. Dr Ventura also holds the positions of Affiliated Professor at Virginia Commonwealth University (Richmond, USA) and Distinguished Adjunct Professor at King Abdulaziz University (Jeddah, Saudi Arabia). Additionally, he is deputy director of the Andalusian Research Institute in Data Science and Computational Intelligence (DaSCI) and heads the Knowledge Discovery and Intelligent Systems Research Laboratory. He has published more than ten books and over 300 articles in journals and scientific conferences. Currently, his work has received over 18,000 citations according to Google Scholar, including more than 2200 citations in 2020. In the last five years, he has published more than 60 papers in international journals indexed in the JCR (around 70% of them belonging to first quartile journals) and he has edited some Springer books “Supervised Descriptive Pattern Mining” (2018), “Multiple Instance Learning - Foundations and Algorithms” (2016), and “Pattern Mining with Evolutionary Algorithms” (2016). He has also been involved in more than 20 research projects supported by the Spanish and Andalusian governments and the European Union. He currently belongs to the editorial board of PeerJ Computer Science, Information Fusion and Engineering Applications of Artificial Intelligence journals, being also associate editor of Applied Computational Intelligence and Soft Computing and IEEE Transactions on Cybernetics. Finally, he is editor-in-chief of Progress in Artificial Intelligence. He is a Senior Member of the IEEE Computer, the IEEE Computational Intelligence, and the IEEE Systems, Man, and Cybernetics Societies, and the Association of Computing Machinery (ACM). Finally, his main research interests include data science, computational intelligence, and their applications.",institutionString:null,institution:{name:"University of Córdoba",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"26",title:"Machine Learning and Data Mining",coverUrl:"https://cdn.intechopen.com/series_topics/covers/26.jpg",isOpenForSubmission:!0,editor:{id:"24555",title:"Dr.",name:"Marco Antonio",middleName:null,surname:"Aceves Fernandez",slug:"marco-antonio-aceves-fernandez",fullName:"Marco Antonio Aceves Fernandez",profilePictureURL:"https://mts.intechopen.com/storage/users/24555/images/system/24555.jpg",biography:"Dr. Marco Antonio Aceves Fernandez obtained his B.Sc. (Eng.) in Telematics from the Universidad de Colima, Mexico. He obtained both his M.Sc. and Ph.D. from the University of Liverpool, England, in the field of Intelligent Systems. He is a full professor at the Universidad Autonoma de Queretaro, Mexico, and a member of the National System of Researchers (SNI) since 2009. Dr. Aceves Fernandez has published more than 80 research papers as well as a number of book chapters and congress papers. He has contributed in more than 20 funded research projects, both academic and industrial, in the area of artificial intelligence, ranging from environmental, biomedical, automotive, aviation, consumer, and robotics to other applications. He is also a honorary president at the National Association of Embedded Systems (AMESE), a senior member of the IEEE, and a board member of many institutions. His research interests include intelligent and embedded systems.",institutionString:"Universidad Autonoma de Queretaro",institution:{name:"Autonomous University of Queretaro",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null},{id:"27",title:"Multi-Agent Systems",coverUrl:"https://cdn.intechopen.com/series_topics/covers/27.jpg",isOpenForSubmission:!0,editor:{id:"148497",title:"Dr.",name:"Mehmet",middleName:"Emin",surname:"Aydin",slug:"mehmet-aydin",fullName:"Mehmet Aydin",profilePictureURL:"https://mts.intechopen.com/storage/users/148497/images/system/148497.jpg",biography:"Dr. Mehmet Emin Aydin is a Senior Lecturer with the Department of Computer Science and Creative Technology, the University of the West of England, Bristol, UK. His research interests include swarm intelligence, parallel and distributed metaheuristics, machine learning, intelligent agents and multi-agent systems, resource planning, scheduling and optimization, combinatorial optimization. Dr. Aydin is currently a Fellow of Higher Education Academy, UK, a member of EPSRC College, a senior member of IEEE and a senior member of ACM. In addition to being a member of advisory committees of many international conferences, he is an Editorial Board Member of various peer-reviewed international journals. He has served as guest editor for a number of special issues of peer-reviewed international journals.",institutionString:null,institution:{name:"University of the West of England",institutionURL:null,country:{name:"United Kingdom"}}},editorTwo:null,editorThree:null}]},overviewPageOFChapters:{paginationCount:19,paginationItems:[{id:"82196",title:"Multi-Features Assisted Age Invariant Face Recognition and Retrieval Using CNN with Scale Invariant Heat Kernel Signature",doi:"10.5772/intechopen.104944",signatures:"Kamarajugadda Kishore Kumar and Movva Pavani",slug:"multi-features-assisted-age-invariant-face-recognition-and-retrieval-using-cnn-with-scale-invariant-",totalDownloads:6,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Pattern Recognition - New Insights",coverURL:"https://cdn.intechopen.com/books/images_new/11442.jpg",subseries:{id:"26",title:"Machine Learning and Data Mining"}}},{id:"82063",title:"Evaluating Similarities and Differences between Machine Learning and Traditional Statistical Modeling in Healthcare Analytics",doi:"10.5772/intechopen.105116",signatures:"Michele Bennett, Ewa J. Kleczyk, Karin Hayes and Rajesh Mehta",slug:"evaluating-similarities-and-differences-between-machine-learning-and-traditional-statistical-modelin",totalDownloads:6,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Machine Learning and Data Mining - Annual Volume 2022",coverURL:"https://cdn.intechopen.com/books/images_new/11422.jpg",subseries:{id:"26",title:"Machine Learning and Data Mining"}}},{id:"81791",title:"Self-Supervised Contrastive Representation Learning in Computer Vision",doi:"10.5772/intechopen.104785",signatures:"Yalin Bastanlar and Semih Orhan",slug:"self-supervised-contrastive-representation-learning-in-computer-vision",totalDownloads:28,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Pattern Recognition - New Insights",coverURL:"https://cdn.intechopen.com/books/images_new/11442.jpg",subseries:{id:"26",title:"Machine Learning and Data Mining"}}},{id:"79345",title:"Application of Jump Diffusion Models in Insurance Claim Estimation",doi:"10.5772/intechopen.99853",signatures:"Leonard Mushunje, Chiedza Elvina Mashiri, Edina Chandiwana and Maxwell Mashasha",slug:"application-of-jump-diffusion-models-in-insurance-claim-estimation-1",totalDownloads:9,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Data Clustering",coverURL:"https://cdn.intechopen.com/books/images_new/10820.jpg",subseries:{id:"26",title:"Machine Learning and Data Mining"}}}]},overviewPagePublishedBooks:{paginationCount:9,paginationItems:[{type:"book",id:"7723",title:"Artificial Intelligence",subtitle:"Applications in Medicine and Biology",coverURL:"https://cdn.intechopen.com/books/images_new/7723.jpg",slug:"artificial-intelligence-applications-in-medicine-and-biology",publishedDate:"July 31st 2019",editedByType:"Edited by",bookSignature:"Marco Antonio Aceves-Fernandez",hash:"a3852659e727f95c98c740ed98146011",volumeInSeries:1,fullTitle:"Artificial Intelligence - Applications in Medicine and Biology",editors:[{id:"24555",title:"Dr.",name:"Marco Antonio",middleName:null,surname:"Aceves Fernandez",slug:"marco-antonio-aceves-fernandez",fullName:"Marco Antonio Aceves Fernandez",profilePictureURL:"https://mts.intechopen.com/storage/users/24555/images/system/24555.jpg",biography:"Dr. Marco Antonio Aceves Fernandez obtained his B.Sc. (Eng.) in Telematics from the Universidad de Colima, Mexico. He obtained both his M.Sc. and Ph.D. from the University of Liverpool, England, in the field of Intelligent Systems. He is a full professor at the Universidad Autonoma de Queretaro, Mexico, and a member of the National System of Researchers (SNI) since 2009. Dr. Aceves Fernandez has published more than 80 research papers as well as a number of book chapters and congress papers. He has contributed in more than 20 funded research projects, both academic and industrial, in the area of artificial intelligence, ranging from environmental, biomedical, automotive, aviation, consumer, and robotics to other applications. He is also a honorary president at the National Association of Embedded Systems (AMESE), a senior member of the IEEE, and a board member of many institutions. His research interests include intelligent and embedded systems.",institutionString:"Universidad Autonoma de Queretaro",institution:{name:"Autonomous University of Queretaro",institutionURL:null,country:{name:"Mexico"}}}]},{type:"book",id:"7726",title:"Swarm Intelligence",subtitle:"Recent Advances, New Perspectives and Applications",coverURL:"https://cdn.intechopen.com/books/images_new/7726.jpg",slug:"swarm-intelligence-recent-advances-new-perspectives-and-applications",publishedDate:"December 4th 2019",editedByType:"Edited by",bookSignature:"Javier Del Ser, Esther Villar and Eneko Osaba",hash:"e7ea7e74ce7a7a8e5359629e07c68d31",volumeInSeries:2,fullTitle:"Swarm Intelligence - Recent Advances, New Perspectives and Applications",editors:[{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser",profilePictureURL:"https://mts.intechopen.com/storage/users/49813/images/system/49813.png",biography:"Prof. Dr. Javier Del Ser received his first PhD in Telecommunication Engineering (Cum Laude) from the University of Navarra, Spain, in 2006, and a second PhD in Computational Intelligence (Summa Cum Laude) from the University of Alcala, Spain, in 2013. He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. 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He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. 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Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. 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Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. 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