Heterogeneous hydrogenation of the aromatic ketones using Ru(II) catalyst
\r\n\t
",isbn:"978-1-83968-571-2",printIsbn:"978-1-83968-570-5",pdfIsbn:"978-1-83968-599-6",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,hash:"dd81bc60e806fddc63d1ae22da1c779a",bookSignature:"Dr. Sebahattin Demirkan",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/10818.jpg",keywords:"Decision Making, Blockchain, Accounting, Earnings Management, Strategic Alliances, Innovation, Performance, Corporate Governance, Accounting Quality, Digital Assets, Internationalization, MNCs",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"January 28th 2021",dateEndSecondStepPublish:"February 25th 2021",dateEndThirdStepPublish:"April 26th 2021",dateEndFourthStepPublish:"July 15th 2021",dateEndFifthStepPublish:"September 13th 2021",remainingDaysToSecondStep:"2 months",secondStepPassed:!0,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"Academician in the area of accounting who believes in the impact of interdisciplinary research. Dr. Sebahattin Demirkan's research interests are in the areas of financial accounting, capital markets, auditing, corporate governance, strategic alliances, taxation, CSR, and data analytics.",coeditorOneBiosketch:"Researcher of strategic management, corporate entrepreneurship, and international business; specific interests include innovation, the ambidexterity framework, inter-organizational relationships, and networks. Experienced in teaching graduate and undergraduate courses in strategy, entrepreneurship, and international business and management areas.",coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"336397",title:"Dr.",name:"Sebahattin",middleName:null,surname:"Demirkan",slug:"sebahattin-demirkan",fullName:"Sebahattin Demirkan",profilePictureURL:"https://mts.intechopen.com/storage/users/336397/images/system/336397.jpg",biography:"Dr. Sebahattin Demirkan is a Professor of Accounting. He earned his Ph.D. in Accounting/Management Science at Jindal School of Management of the University of Texas at Dallas where he got his MS in Accounting, MSA Supply Chain, and MBA degrees. He got his BA in Economics and Management at the Faculty of Economics and Administrative Sciences at Bogazici University, Istanbul. He worked at Koc Holding, a private venture capital firm, and the University of California, Berkeley during and after his education at Bogazici University. His research interests are in the areas of financial accounting, capital markets, auditing, corporate governance, strategic alliances, taxation, CSR, and data analytics. Dr. Sebahattin Demirkan has published articles in Contemporary Accounting Research, JAPP, JAAF, TEM, Journal of Management, and other top academic journals. He teaches several different classes in both undergraduate and graduate levels in Accounting and Analytics programs. He is a treasurer and vice president of the TASSA, board member of the BURCIN and member of the American Accounting Association.",institutionString:"Manhattan College",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Manhattan College",institutionURL:null,country:{name:"United States of America"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"7",title:"Business, Management and Economics",slug:"business-management-and-economics"}],chapters:[{id:"75977",title:"The Economic Effect of Bitcoin Halving Events on the U.S. Capital Market",slug:"the-economic-effect-of-bitcoin-halving-events-on-the-u-s-capital-market",totalDownloads:26,totalCrossrefCites:0,authors:[null]}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"301331",firstName:"Mia",lastName:"Vulovic",middleName:null,title:"Mrs.",imageUrl:"https://mts.intechopen.com/storage/users/301331/images/8498_n.jpg",email:"mia.v@intechopen.com",biography:"As an Author Service Manager, my responsibilities include monitoring and facilitating all publishing activities for authors and editors. 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Furthermore, molecular hydrogen is without doubt the cleanest reducing agent, with complete atom efficiency. Therefore, the catalytic, asymmetric hydrogenation (AH) of prochiral ketones is the most practical and simplest method to access enantiomerically enriched secondary alcohols, on both the laboratory and industrial scales. Asymmetric transfer hydrogenation (ATH), on the other hand, represents an attractive alternative or complement to hydrogenation because it is easy to execute and a number of cheap chemicals can be used as hydrogen donors. For practical use and to address environmental issues a high catalyst activity (low loadings) and selectivity is preferable, as well as the employment of ‘’greener’’ solvents, mild operating conditions and recyclable catalyst systems. High turnover numbers (TONs) and turnover frequencies (TOFs), and satisfactory stereo- and chemoselectivities are attainable only with a combination of well-defined metal catalysts and suitable reaction conditions. The reactivity and selectivity can be finely tuned by changing the bulkiness, chirality and electronic properties of the auxiliaries on the metal center of the catalyst.
Since the application of very efficient, chiral BINAP-derived ruthenium complexes in the AH of functionalized ketones (β-keto esters) at a high enantioselectivity level in the homogenous phase (Noyori et al., 1987), the development of more robust and reactive molecular catalysts is still highly desirable. Furthermore, because of the structural and functional diversity of organic substrates, no universal catalysts exist. Ruthenium complexes bearing chiral ligands are among the most commonly used catalysts for AH and ATH, following by rhodium and iridium, although in recent times other transition metals, like Fe, Cu, or Os have rapidly penetrated this field.
A major breakthrough in the wide-scope AHs of ketones was the discovery by Noyori and co-workers of the conceptually new and extremely efficient ruthenium bifunctional catalysts. They found that simple ketones like 1-5, which lack anchoring heteroatoms capable of interacting with a metal center, can be reduced enatioselectively with H2 (1-8 atm) in
Simple ketones in chemoselective AH catalyzed by bifunctional catalysts of type C1
The XylBINAP-complex C2 proved to be very effective for the stereoselective hydrogenation of heteroaromatic ketones (2-furyl, 2- and 3-thienyl, 2-thiazolyl, 2-pyrrolyl, 2-, 3- and 4-pyridinyl) as well as aromatic-heteroaromatic and bis-heteroaromatic ketones (phenyl-thiazolyl, phenyl-imidazolyl, phenyl-oxazolyl, phenyl-pyridinyl, pyridinyl-thiazolyl) thus providing a plethora of structurally interesting heterocyclic alcohols (C. Chen et al., 2003; Ohkuma et al., 2000). In fact, the complex C2 has been established as one of the most efficient and selective pre-catalysts for the AH of a variety of ketones (Ohkuma et al., 1998) until the discovery of novel ruthenabicyclic complexes (Matsumura et al., 2011). The hydrogenation of acetophenone catalyzed by the ruthenabicyclic complex C3 with a substrate-to-catalyst molar ratio (S/C) 10000 under 50 atm of H2 in a
Ruthenabicyclic
Since the Noyori’s standard Ru(II) complexes of the type C1 require the presence of a strong base as a co-catalyst to
The extremely high reactivity and enantio-selectivity of [TunesPhos-Ru(II)-(1,2-diamine)] complexes combined with
Highly active ruthenium catalysts
The discovery of new classes of hydrogenation catalysts that deviate from the Noyori-type C1 may represent a good opportunity to reduce every type of ketone substrate with high reactivity and selectivity. Indeed, while the conventional [BINAP-Ru-(1,2-diamine)] catalysts have shown poor reactivity and enantio-selectivity in the hydrogenation of sterically congested
Interestingly, a combined amine-benzimidazole ligand in the complex C7 influenced the reverse enantioselection from that typically observed in the AH of ring-substituted acetophenones and allowed the reduction to proceed in nonprotic solvents (toluene/
AH of sterically congested and poorly reactive ketones
AH using non-phosphine-based catalysts is attractive due to the toxicity of the catalyst precursors and the product contamination when Noyori-type catalysts are used. However, the efficiency of the π-allyl Ru precursor in combination with the phosphorous-free pyridyl-containing ligand L1 did not exceed that of the original [BINAP-Ru-diamine] complexes (Fig. 4) (Huang et al., 2006). Interestingly, this new catalyst system catalyzes the hydrogenation of 1-indanone only in the absence of a base.
The most efficient AH catalysts tend to mimic that of Noyori as its excellent enantioselectivity is proposed to be a result of the synergistic effect of chiral phosphane and chiral amine ligands. Nevertheless, commercially available achiral diphosphanes (DPPF, DPEphos) in conjunction with rigid chiral biisoindoline-based diamines have been applied in the Ru-catalyzed AH of (hetero)aromatic ketones, affording excellent enantioselectivities (up to 99%
Since ketones coordinate more weakly to metals than olefins, many Rh-phosphane complexes show no activity for hydrogenation of simple ketones. However, the highly enantioselective direct hydrogenation of simple ketones 19−24 using an
The complex prepared from [Rh(COD)OCOCF3)]2 and the amide-phosphine-phosphinite ligand L3 catalyzed the AH of trifluoromethyl ketones 25 giving almost quantitative yields of the corresponding alcohols in 83-97%
Rh-catalyzed AH of simple and fluorinated ketones
The hydrogenation of ketones catalyzed by chiral iridium complexes has been well studied and developed because iridium is less expensive than rhodium (Malacea et al., 2010). Generally, Ir(I) or Ir(III) complexes with chiral diamines, diphosphines or a combination of both, very similar to those in Ru-catalyzed hydrogenation, have been successfully employed in the AH of various aromatic ketones and β-keto esters. On the other hand, chiral Ir(I) complexes bearing N-heterocyclic carbenes as ligands proved to be far less efficient (Diez & Nagel, 2009). Although complexes of [Ir(COD)Cl]2 and planar-chiral ferrocenyl phosphine-thioethers (
Ir-catalyzed AH
With its origin in Meerwein-Pondorf-Verley reduction, and later developed in its asymmetric version, the transfer hydrogenation of ketones has emerged as an operationally simpler and significantly safer alternative to catalytic H2-hydrogenation as there is no need for special vessels and high pressures (Ikariya & Blacker, 2007; Palmer & Wills 1999). Moreover, chemo-, regio- and stereoselectivity can often be different from that of AH. In the ATH process, the transition-metal catalyst is able to abstract a hydride and a proton from the hydrogen donor and deliver them to the carbonyl moiety of the ketone. Suitable catalysts for ATH are typically complexes of homochiral ligands with Ru, Rh or Ir, whilst
In parallel with the discovery of efficient ruthenium catalysts for AH, Noyori and co-workers found a prototype of chiral (arene)Ru(II) catalysts of type C8 bearing
The stereochemically rigid β-amino alcohols L7 or L8 work very well as ligands for Ru-catalyzed ATH in basic
An
It was first disclosed by Noyori, that a N-H moiety is necessary for an efficient transfer of hydrogen from the metal hydride. However, the Ru complex with the oxazolyl-pyridyl-benzimidazole-based NNN ligand L10 featuring no N-H functionality exhibited a high catalytic activity in the ATH of different acetophenones (Fig. 7) (Ye et al., 2011).
Another type of ligands lacking a basic NH group like L11 are based on a combination of
The combination of [RuCl2(
Selected ligands for ATH
There is a continuing search for stable catalysts that would not degrade easily during the hydrogenation process, thus making it possible to execute as many as possible catalytic cycles. In this respect, the covalent linkage from the diamine to the
It has been shown that the Rh complex with the ‘’achiral’’ but tropos benzophenone-derived ligand L14 and a chiral diamine activator (
The unique phenomenon of an enhancement of the enantioselectivity by using the chiral bulky alcohol (
ATH catalyst systems
Although Ru(II) complexes have enzyme-like properties reaching high TONs and TOFs, many times near to room temperature, and deliver the secondary alcohols in near-quantitative
The first hydrogenation of ketones catalyzed by a well-defined iron catalyst was effected with an iron hydride Shvo-type complex C14 (Casey & Guan, 2007), while later on Morris and co-workers succeeded in the ATH of simple ketones catalyzed by iron complexes containing chiral PNNP tetradentate ligands, attaining
An asymmetric Shvo-type iron complex C17 was found to be a very poor catalyst for the transfer hydrogenation of acetophenone with FA/TEA, since after 48 hours only a 40% conversion and a 25%
Enantioselective, copper-catalyzed homogenous H2-hydrogenation was introduced by Shimizu and co-workers, who used a catalyst system based on [Cu(NO3){P(3,5-Xylyl)3}2], (
Selected iron catalysts
Owing to the stronger bonding of Os compared to Ru, robust and thermally stable complexes can be obtained, which is important for achieving highly productive catalysts. Os(II) CNN pincer complexes C18 exhibited a high catalytic activity and productivity in both the AH (5 atm H2/
Ligands for Cu-mediated hydrogenation and Os-complexes
As a consequence of the increasing demand for ‘’greener’’ laboratory and industrial applications, the development of water-operating catalytic systems for the asymmetric hydrogenation of ketones has been of great interest (Wu & Xiao, 2007). The main disadvantage, however, is the low solubility of the homogenous metal catalysts and most of the organic substrates when going from organic to aqueous media, which may be reflected in a reduced activity and selectivity. To circumvent this, either hydrophilic, often charged, functionalities can be introduced to ligands to render the catalysts water-soluble, or different surfactants can be added in order to solvate the reaction partners, although in some cases water-insoluble catalysts can deliver a superior activity and selectivity.
Water-soluble Ru, Ir or Rh catalysts were prepared
Selected ligands and complexes for aqueous hydrogenation
Surfactants are often added as co-solvents to obtain a sufficient solubility of the reactants, products and metal catalysts, thus retaining the activity and selectivity of the hydrogenation process. The ATH of ketones, particularly -bromomethyl aromatic ketones, was successfully performed with HCO2Na by employing the unmodified and hydrophobic Ru-, Rh- and Ir-TsDPEN complexes C22 and C23 in the presence of single-tailed, cationic and anionic surfactants and to form micelles and vesicles (Fig. 11) (Wang et al., 2005). It is notable that catalysts embedded in these micro-reactors can be separated from the organic phase and reused for at least six times without any loss of activity and enantioselectivity.
In recent years ionic liquids (ILs) have attracted an increasing interest because of their non-volatility, non-flammability and low toxicity. Additionally, ILs are capable of immobilizing homogenous catalysts and facilitating the recycling of catalysts. Ideally, organic products can be easily separated by extraction with a less polar solvent and the IL phase containing catalyst can be reused. Such an immobilization of catalysts also promises to prevent the leaching of toxic metals into the organic products, which is especially desirable in the production of pharmaceutical intermediates.
Various aromatic ketones were reduced with FA/TEA in an ionic liquid L25 at 40 °C, catalyzed by an
While for the AH of β-alkyl β-ketoesters high enantioselectivities can be attained by using the Ru-BINAP system, for the analogous β-aryl ketoesters much more inferior
Hydrogenation in ionic liquids
Homogenous hydrogenation and transfer hydrogenation may be mechanistically closely related because both reactions involve a metal hydride species under catalytic conditions, thus sharing a multistep pathway of hydride transfer to the ketone,
Noyori and co-workers proposed metal-ligand bifunctional catalysis for their Ru catalysts containing chiral phosphine-amine ligands and for (arene)Ru-diamine catalysts, which consequently resulted in a widely accepted mechanism to be responsible for the highly enantio-selective hydrogenation and transfer hydrogenation of prochiral ketones (Noyori et al., 2001, 2005). The actual catalysts, Ru-hydrides 31 or 34, are usually created in a basic alcoholic solution (under H2 or not) at the beginning of the catalytic reaction from the Ru precursors 30 or 33. Note that only the
Outer-sphere hydridic route for bifunctional catalysts
Depending on transition-metal catalysts, an ionic mechanism has also been proposed where the proton and hydride transfer occur in separate steps (Bullock, 2004).
The active species in catalytic cycles, Ru-hydride (31 or 34) and Ru-amido complexes (32 or 35), have not only been detected but also isolated in some cases (Abdur-Rashid et al., 2001, 2002; Haack et al 1997).
The absolute configuration of the alcohol product in AH is determined in the six-membered transition state resulting from the reaction of a chiral diphosphine-diamine-RuH2 complex with a prochiral ketone (Noyori et al., 2005). Because the enantiofaces of the ketone are differentiated on the molecular surface of the saturated RuH2 complex, a suitable combination of the catalyst and substrate is necessary for high efficiency. The prochiral ketone (
The stereoselectivity in the hydrogenation of prochiral aryl ketones catalyzed by (arene)Ru(II) complexes (mostly in ATH) has been ascribed not only to the chiral environment originating from the amine ligand, but also to the contribution of the arene ligand to the stabilization of the transition state through the CH/π interaction (Fig 14 (b)) (Yamakawa et al., 2001). This interaction as well as the NH/π interaction occurring in the transition states with diphosphine-Ru-(1,2-diamine) systems may explain why aryl ketones usually give better
Depending on the ligands attached to the metal center (M = transition metal) the inner-sphere mechanisms, in which monohydride or dihydride species are involved, can operate in H2-hydrogenation and transfer hydrogenation (Clapham et al., 2004, Samec et al., 2006; Wylie et al., 2011). In contrast to the outer-sphere mechanism, here the ketone and alcohol interact with the metal center.
Enantiodifferentiation in the bifunctional-catalyzed hydrogenation of acetophenone
For the heterogeneous, asymmetric, catalytic reduction of the C=O functionality, there are two types of heterogeneous catalysts. One is chirally modified supported metals, and the other is the immobilized homogeneous catalyst on a variety of organic and inorganic polymeric materials. There are also two major reasons for preparing and studying heterogeneous catalysts: firstly, and most importantly, the better and advanced separation and handling properties, and, secondly, the potential to create catalytic positions with an improved catalytic performance. The ultimate heterogeneous catalyst can easily be renewed, reused without of loss of activity and selectivity, which are at least as good or even better than those of the homogeneous analogue.
The immobilization of a homogeneous metal coordination complex is a useful strategy in the preparation of new hydrogenation catalysts. Much effort has been devoted to the preparation of such heterogenized complexes over the past decade due to their ease of separation from the reaction mixture and the desired minimal product contamination caused by metal leaching, as well as to their efficient recyclability without any significant loss of activity. Preferably, Rh, Ir, and Ru complexes have been employed in the hydrogenations of carbonyl functionality (Corma et al., 2006). Chemically different supports have been used for the immobilization of various homogeneous complexes, including polymeric organic and inorganic supports (Saluzzo et al., 2002; Bergbreiter, 2002; Fan et al., 2002). Due to their chemical nature, organic polymeric supports have some drawbacks concerning reduced stability that affects the reusability of the catalysts, mainly due to their swelling and deformation (Bräse et al., 2003; Dickerson et al., 2002). Supports of an inorganic nature are more suitable owing to their physical properties, chemical inertness and stability (with respect to swelling and deformation) in organic solvents. The above-mentioned properties of the inorganic supports will facilitate the applications of the materials in reactions carried at higher temperatures and their use in continuous-flow reactions. In the past decade a lot of research effort has been devoted to the development of adequate procedures to attach homogenous catalysts onto inorganic supports (Merckle & Blümel, 2005; Crosman et al., 2005; Corma et al., 2005; Jones et al., 2005; Melero et al., 2007). Immobilization via covalent bonds is undoubtedly the most convenient, but on the other hand, it is the most challenging method for immobilization to perform on such supports (Jones et al., 2005; Steiner et al., 2004; Pugin et al., 2002; Sandree et al., 2001). For example, micelle templated silicas (MTS) featuring a unique porous distribution and high thermal and mechanical stabilities can be easily functionalized by the direct grafting of the functional organo-silane groups on their surfaces (McMorn & Hutchings, 2004; Heckel & Seebach, 2002; Bigi et al., 2002, Clark & Macquarrie, 1998; Tada & Iwasawa, 2006). On the other hand, polar solvents such as water or alcohols and high temperatures during the catalytic procedure can promote the hydrolysis of the grafted moieties.
The heterogenized catalysts can potentially combine the advantages of both homogenous and heterogeneous systems. In 2003, Hu and coworkers developed a novel chiral porous solid catalyst based on zirconium phosphonates for the practically useful enantio-selective hydrogenation of unfunctionalized aromatic ketones (Fig. 15) (Hu et al., 2003a).
Schematic presentation of chiral porous Zr-phosphonate-Ru-(
With the built-in Ru-BINAP-DPEN moieties, porous solids of Ru-(
Substrate | Ru-( | Ru-( | MNP | MNP |
Ar = Ph, R = Me | 96.3 | 79.0 | 87.6 | 81.7 |
Ar = 2-naphtyl, R = Me | 97.1 | 82.1 | 87.6 | 82.0 |
Ar = 4- | 99.2 | 91.5 | 95.1 | 91.1 |
Ar = 4-MeO-Ph, R = Me | 96.0 | 79.9 | 87.6 | 77.7 |
Ar = 4-Cl-Ph, R = Me | 94.9 | 59.3 | 76.6 | 70.6 |
Ar = 4-Me-Ph, R = Me | 97.0 | 79.5 | 87.9 | 80.5 |
Ar = Ph, R = Et | 93.1 | 83.9 | 88.9 | 86.3 |
Ar = Ph, R = | 90.6 | – | – | – |
Ar = 1-naphtyl, R = Me | 99.2 | 95.8 | – | – |
Heterogeneous hydrogenation of the aromatic ketones using Ru(II) catalyst
Heterogeneous chiral Ru(II)-TsDPEN-derived catalysts based on Noyori’s (1
Heterogeneous RuII mesoporous silica-supported catalysts
Additionally, Li and coworkers (J. Li et al., 2009) developed a Ru(II)-TsDPEN-derived catalyst that was immobilized in a magnetic siliceous mesocellular foam material. The heterogeneous catalyst showed comparable activities and enantioselectivities (
Ir and Ru mesoporous silica-supported catalysts
Chiral Ru and Ir, mesoporous, silica-supported catalysts were introduced by Liu and coworkers (G. Liu et al., 2008a, 2008b). The Ir-C28-SBA-(
Two magnetic chiral Ir and Rh catalysts were prepared
Magnetic Ir and Rh chiral catalysts
The mesoporous SBA-15 anchored 9-amino
The chiral RuCl2-diphosphine-diamine complex with siloxy functionality was successfully immobilized on mesoporous silica nanospheres with three-dimensional channels (Fig. 19) (Mihalcik & Lin, 2008). Upon activation with
Chiral RuCl2-diphosphine-diamine complexes immobilized on mesoporous silica nanospheres
Differently substituted Rh complexes were anchored on an Al2O3 support and applied for the enantioselective C=O hydrogenation with reasonable activity and enantioselectivities with
The immobilization of the rhodium complexes [Rh((
Furthermore, a series of polystyrene-supported TsDPEN ligands were prepared in one step and converted to the corresponding Ru(II) complexes by a treatment with [RuCl2(
A series of dendrimers and hybrid dendrimers based on Noyori-Ikariya’s TsDPEN ligand were prepared and the application of their Ru(II) complexes in the ATH of acetophenones was studied. A high catalytic activity and completely maintained enantio-selectivity (acetophenone, 93.4-98.2%
Among various approaches for homogeneous catalyst immobilization, the “self-supported” strategy exhibits some relevant characteristics, such us easy preparation, good stability, high density of catalytically active sites, and high stereocontrol performance, as well as simple recovery (Dai, 2004; Ding et al., 2007). Self-supported Noyori-type catalysts C37-C40 for the AH of ketones by the programmed assembly of bridged diphosphine and diamine ligands with Ru(II) ions were developed (Fig. 20) (Liang et al., 2005; Liang et al., 2006). The enantioselectivity of the hydrogenation of the aromatic ketones under the catalysis of the self-supported catalyst C40 was in some cases significantly higher than the
A very interesting example is the asymmetric synthesis of the chiral alcohol function that makes use of the strength of ion pairing in ionic liquids (Schulz et al., 2007). The hydrogenation of substrate 46 using H2 (60 bar) at 60 oC in the presence of the heterogeneous, achiral catalyst Ru/C in an ethanolic solution, gave the corresponding hydroxyl-functionalized ionic liquid in a quantitative yield and up to 80%
Self-supported Noyori-type catalysts C37-C40 for the AH of ketones
Enantio-selective hydrogenation of a keto-functionalized ionic liquid
Importing chirality to a catalytic active metal surface by the adsorption of a chiral organic molecule (often referred to as a chiral modifier) seems to be one of the promising strategies to obtain new chiral heterogeneous catalytic systems. In the hydrogenation of C=O function, chirality-modified supported metal catalysts represent a promising approach with synthetic potential. Orito et al. introduced the strategy of a cinchona-alkaloid-modified platinum catalyst system in 1979 (Orito et al., 1979). Following the early work of Blaser et al. (Studer et al., 1999, 2000, 2003; Blaser et al., 2000), Baiker et al. (Heinz et al., 1995, von Arx et al., 2002), and others, the methodology developed in the sense of the substrate scope, and on the other hand, extensive efforts were carried out to get more insight into understanding the mechanistic aspects of the transformation. The method was found to have excellent performance in the hydrogenation of activated ketones (Fig. 22).
The modifiers derived from CD and quinine (QN) lead to an excess of (
A systematic structure-selectivity study of the hydrogenation of activated ketones catalyzed by a modified Pt-catalyst revealed a high substrate specificity of the catalytic system. Relatively small structural changes in the substrate or modifier can strongly affect the enantio-selectivity and often in the opposite manner, especially when comparing reactions in toluene and AcOH (Exner et al., 2003). Fluorinated β-diketones can be enantioselectively hydrogenated on cinchona-alkaloids-modified Pt/Al2O3 catalysts. Methyl, ethyl, and isopropyl 4,4,4-trifluoroacetoacetates were hydrogenated in the presence of MeOCD-modified Pt/Al2O3 catalysts, producing the corresponding alcohols in 93-96%
Synthetically obtained (
Enantio-selective hydrogenation of activated ketones.
A supported (SiO2) iridium catalyst, which is stabilized by PPh3 and modified by a chiral diamine, derived from cinchona alkaloids, exhibits a high activity and high enantioselectivity for the hydrogenation for the simple aromatic ketones (Fig. 23). The addition of different bases (
Enantioselective hydrogenation of activated ketones.
A series of silica (SiO2) supported iridium catalysts stabilized by cinchona alkaloids were also prepared and applied in the heterogeneous asymmetric hydrogenation of acetophenone. Cinchona alkaloids display a substantial capability to stabilize and disperse the Ir particles. A synergistic effect between the (
Besides improving the cinchonidine-platinum catalyst system, extensive efforts have been made in developing a reliable mechanistic interpretation. To understand the adsorption behavior of the modifier and reactant, their conformation, and their intra-molecular interactions at solid-liquid interface, an
Schematic representation of the adsorption mode of CD on the metal surface and interactions between the half-hydrogenated state of the activated ketone and the basic quinuclidine-N atom of the chiral modifier.
An inversion of the enantioselectivity occurs in the asymmetric hydrogenation of the activated ketones by changing the solvent composition, including water and acid additives (von Arx et al., 2001b; Bartók et al., 2002). Hydrogenation of the ethyl pyruvate over Pt/Al2O3 (Huck et al., 2003a) and 4-methoxy-6-methyl-2-pyrone over Pd/TiO2 (Huck et al., 2003b), an equimolar mixture of cinchona alkaloids CD and QD resulted in
This chapter discusses the transition-metal-catalyzed, asymmetric, homogenous and heterogeneous hydrogenation of prochiral ketones, not so much focusing on the reactions providing valuable chiral alcohols, but rather it gives prominent and interesting examples of the ketone substrates and catalyst systems that are found in the recent literature. Despite the tremendous effort being made in the catalytic, asymmetric hydrogenation of prochiral ketones, approaching the enzymatic performance in some cases, there is still much potential for the continued development of these reactions. Concerning the environmental and economic issues, the introduction of non-toxic, cheap, and at the same time efficient and universal catalyst systems, being able to operate under mild conditions in a highly selective manner and for a broad range of substrates, remains a challenge for future research. Additionally, more rational catalyst designs are possible with better mechanistic understandings of the catalytic cycles in catalytic AH and ATH reactions.
The Ministry of Higher Education, Science and Technology of the Republic of Slovenia, the Slovenian Research Agency (P1-0230-0103), EN→FIST Centre of Excellence, and Krka, Pharmaceutical company, d.d. are gratefully acknowledged for their financial support.
Glaucoma is a progressive optic neuropathy where intraocular pressure is considered to be the most significant risk factor in its etiopathogenesis. The fundamental pathology of the disease is the progressive loss of the ganglion cells. Glaucoma predominantly affects the inner macular retinal layers: the macular RNFL (mRNFL), ganglion cell layer (GCL) and inner plexiform layer (IPL) where ganglion cell complex (GCC) consists of RNFL, GCL and IPL thickness [1]. The ganglion cell damage occurs at the lamina cribrosa level in the optic disc; first, the axons get damaged, then the ganglion cells which these axons are connected to disappear through a programmed cell death called apoptosis. This loss of axons and ganglion cells cannot be identified with any clinical diagnosis methods before it exceeds a certain critical threshold [2, 3, 4, 5]. Research in this area shows that the earliest symptom that can be detected clinically in glaucoma is the loss or thinning of the retinal nerve fiber layer (RNFL). The loss or thinning of the neuroretinal tissue is usually detected later on [6, 7, 8].
\nCircumpapillary RNFL (cpRNFL) and GCC thickness measurements are the parameters that have high performance in detecting glaucoma-detecting ability and are comparable to cpRNFL thickness [9, 10, 11].
\nOCT is an imaging method that obtains high-resolution sections of biological tissues, and it is possible to simply define this mechanism as the conversion of the light that is reflected from the tissue to an image [12, 13, 14].
\nCommonly used in the area of ophthalmology especially in the past 20 years, the optical coherence tomography (OCT) has provided significant contributions for the early diagnosis of the glaucoma disease and monitoring and analysis of the glaucoma patients [14, 15, 16, 17, 18].
\nOCT is first developed by Huang et al. in 1991, at the Massachusetts Institute of Technology in Boston [19]. Studies of Dr. Fujimoto who was an important member of the team who developed OCT, on femtosecond lasers and interferometers that can release energy in very short periods of time have been defining in terms of the development of the device [20]. The first OCT device known as the OCT-1 has been introduced by a company called Humprey, which was acquired by Carl Zeiss in 1991. In the following years, OCT-2, which had an increased resolution, and finally OCT-3 (Stratus OCT) were developed. All three devices are referred to as time domains [21, 22, 23, 24].
\nThis term is used more commonly, especially after the spectral domain (Fournier domain) OCT technology became available in 2002, in order to clarify the difference between the two technologies. OCT-3 is the last manufactured product with the time domain technology, which provides a significant increase in resolution compared to OCT-1 and OCT-2 [25, 26].
\nToday, all OCT devices that are manufactured have the spectral domain technology. Simply put, while the operating principle of time domain OCT is associated with the delay in the reflection time of light, the actual variable in spectral domain OCT is the change in the optic frequency. The important differences between these devices that demonstrate themselves on clinical basis are the high axial resolution, being affected by eye movements at a minimum level and low artifacts. To date, axial resolution obtained through spectral domain OCT devices has reached up to a value of 3 microns, and these devices are rightfully referred to as OCTs with very high speeds and very high resolutions [27, 28].
\nAs also mentioned earlier, the OCT calculates the delay in the reflection of light from different layers of the tissue. Light reflected from the deep layers of the tissue would exhibit a longer period of delay, compared to that of the light reflected from the surface. The distribution of the intensity of the reflected light according to this period of delay is demonstrated as the axial A-mode scan. Many A-mode scans are obtained through scans across the sample, and these are converted into gray or colored scales indicating the signal intensity [29, 30].
\nThe most critical issue for the formation of the image in OCT systems is the measurement of the time difference of the lights reflecting from different tissues, that is, the reflection delay. A reference mirror which provides the time difference is available in time domain OCTs. This mobile mirror system is a factor that limits the speed of obtaining an image in OCT. In the spectral domain OCT system on the other hand, the mirror is fixed. Thanks to this feature, the mirror movement which limits the speed is avoided [31].
\nIn all OCT systems manufactured since the clinical use of the OCT technology, super luminescent diodes (SLDs) have been used as sources of light. In time domain OCT-3 whose axial resolution in the tissue is the highest, the resolution value is approximately 8–10 microns. Super luminescent diode lasers that could be different from each other but similar to each other in terms of the range of wave light emissions are also used in spectral domain OCT devices. Axial resolution in these devices has been lowered up to 3 microns [14].
\nThanks to the development of the spectral domain OCT technology, the speed for obtaining images has also increased and risen up to 70,000 A-mode scans per second from 400 A-mode scans (OCT-3) per second. The increase in the scan speed has lowered the amount of the artifact in the image even further [32].
\nThere are several OCT devices working with similar principles but vary in diagnostic ability, acquisition speed and resolution. In this section, three commonly used SD-OCTs that are the Spectralis (Heidelberg Engineering, Dossenheim, Germany), the Cirrus (Carl Zeiss Meditec, Dublin, CA) and the RTVue (Optovue Inc., Fremont, CA) and their features are discussed. Several studies have addressed the diagnostic accuracy of the SD-OCTs one by one or compared them to time-domain technology [1, 14, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42].
\nSince RNFL is, without a doubt one of the most important factors which is also discussed extensively in the literature, a comparison between the protocols through this value will be made and the diagnostic accuracy of this value will be examined [27].
\nHowever, in recent studies comparing protocols on the capability of OCT in the diagnosis of glaucoma, no significant differences were observed between the protocols [14, 31, 32].
\nCirrus TM High Definition (HD)-OCT Spectral Domain (Carl Zeiss Meditec, Dublin; CA) used for the analysis of glaucoma.
\nAt present, Cirrus high-definition (HD)-OCT is a widely used device to evaluate circumpapillary RNFL (cp-RNFL) thickness in clinical practice similarly as RTVue-100.
\nIt is possible for us to find the necessary quantitative and qualitative data for a good management of glaucoma in this OCT device. It allows us to study the morphology and manometry of the optic disc and the peripapillary nerve fibers [37].
\nEven the first generation of these devices was able to display the retinal layers for us in vivo during the RNFL thickness measurement. In fact, many studies have shown the similarity between the OCT measurements and the histological sections. For this reason, the thickness of the RNFL is crucial for the early diagnosis of glaucoma and for being able to have an opinion on its progression [27, 29].
\nCirrus Zeiss TM HD-OCT is an advanced technology in glaucoma research which is easy to use. It is possible for us to obtain precise and thorough information about the peripapillary area and the RNFL with this system [38, 39]. Main scanning models are provided below.
\nOptic disc is recorded by Cirrus Zeiss TM HD-OCT within a 6x6 mm cube consisting of 200-B mode scans, each of which consists of 200-A mode scans. This area is divided into sections for analysis. (Figure 1).
\nOptic disc scanning in Cirrus Zeiss.
The device automatically identifies the center of the optic disc through data in this cube and forms a 3.46 mm circle around the disc, which enables the RNFL thickness around the peripapillary ring to be analyzed and compared with normative data. The most important point here is the ability to perform RNFL analysis with a reliable level of precision repetitively, even though the optic disc is not placed in the center during the scan.
\nSignal Power.
\nThe value of the signal power is a value between 0 and 10 for the entire scan, with 10 being the maximum value. The threshold value is 5 and signal power values lower than that represent the values that are below the acceptable threshold value. In some patients, it may not be possible to obtain high signal power. In such cases, the clinician should assess whether the signal obtained for scan analyses are acceptable or not.
\nWhile the fundus image is being created, the fundus image obtained through scanning laser ophthalmoscopy and the OCT fundus image are superimposed. This image appears on the upper section of the RNFL analysis screen. (Figure 2) The location of the calculation ring for the temporal, superior, nasal, inferior and temporal (TSNIT) section analyses is displayed in red. The operator can adjust the location of this ring following the shot if she/he likes to; however, that is often not necessary since this task is usually performed accurately through the automatic centering functionality. The B-mode scan image is the calculation ring generated from the cube of data and is flattened for the TSNIT orientation.
\nRNFL analysis screen in Cirrus Zeiss.
The RNFL thickness map is calculated based on all the data of the scanned cube. The color scale used here is similar to that of a topographic map, where cold colors represent thinned areas while hot colors represent thick areas. In this way, the RNFL thickness at all points of the 6 × 6 mm area can be seen. The map excludes the optic disc displayed in dark blue. (Figure 3).
\nRNFL thickness map in Cirrus Zeiss.
In the color scale used to demonstrate the normal and defective areas in the RNFL, thickness of the nerve fiber layers ranging from zero (blue) to 350 μm (white) are indicated using color codes.
\nThe RNFL thickness across the TSNIT calculation ring is also displayed in a numerical chart format. In this chart, the average thickness of each point across the calculation is demonstrated for both eyes. (Figure 3) In addition, average thickness for each quadrant is also demonstrated separately and in time zones. Ultimately, in all these charts, the values of the patient are compared to normative data.
\nThe TSNIT thickness profile demonstrates the RNFL thickness for each point across the peripapillary ring and compares these values to the normative database. In these comparisons of patients in the same age group, color codes (white, green, yellow and red) are used. (Figure 3).
\nThe RNFL normative database is used for glaucoma patients who are older than 18. This database allows us to compare the patient’s data in the area that we are clinically interested in, with the data of other individuals in the same age group.
\nIn order to demonstrate the normal distribution percentages of the individuals in the same age group, the RNFL normative database uses the colors as below:
\nRed: The lowest portion of 1% with regard to all measurements is in the red zone and these indicators must be considered as abnormal.
\nYellow: In case the measurements are within the lowest portion of 5%, they are displayed in yellow and should be interpreted as doubtful.
\nGreen: 90% of all measurements are in this section and should be considered as normal.
\nThe patient’s RNFL thickness is compared with the normative data through the deviation map. Data that are out of the range of normal values are displayed in red and yellow as described earlier.
\nThe analysis of the results for glaucoma can be easily performed at a single glance with this device. On the first row, the fundus images are provided at the top, followed by the B-mode images of the peripapillary area neighborhood. On the second row, the map of the thickness of the nerve fibers is provided, accompanied by the deviation map indicating the difference between the normal thickness and the measured thickness. On the third row, rings indicating the thickness of the nerve fibers in the quadrants are provided. On the fourth row, a colored table where the thickness of nerve fibers is indicated in microns and that allows us to understand if the values are within the normal (green), doubtful (yellow) or pathological (red) range, thanks to different colors, is provided. In the resulting analysis, data for the right eye are provided on the left, while data for the left eye are provided on the right.
\nIn conclusion, Cirrus Zeiss TM HD-OCT device offers us good qualitative and quantitative information about the glaucomatous damage in patients [42, 43, 44]. However, the diagnosis and follow-up of glaucoma can be quite complicated at times. Therefore, since making a diagnosis with one device can mislead the physicians especially in difficult cases, comprehensive clinical exam data including the patient’s visual field must be gathered while making a diagnosis.
\nIn glaucoma research, four scanning models for the Optovue-RTVue spectral domain OCT (RTVue Optovue Inc. Fremont, CA) device are used.
\nThe optic disc is calculated through a 6 × 6 mm cube consisting of 101 lines. 3D optic disc scanning is used especially for the formation of reference lines and the determination of optic disc veins. The 3D reference line represents the optic disc limits created automatically by a software that uses the 3D optic disc scan.
\nIn this protocol, 13 circular and 9 radial scans with 1.3–4.9 mm diameters around the optic disc head are performed. These scans limit the area between the retinal pigment epithelium and the optic disc head. Here, the device automatically calculates the center of the optic disc and not the center of the scan itself. The same calculation is also automatically used in progression maps (Figure 4).
\nOptic disc head map in RTVue.
The map of the optic disc head provides significant information about the morphology of the optic disc. It provides insight, especially on the cup-to-disc ratio of the optic disc, the 3.45 mm circular RNFL area whose center is the optic disc head and the RNFL area located at the rim of the optic disc, 2 mm away.
\nThis scan is used to analyze the RNFL and it has shown that RNFL parameters of the RTVue-100°CT has good specificity for the detection of glaucoma [45]. The RNFL scanning pattern completes four circular scans with diameters of 3.45 mm in 0.16 s by aiming for the optic disc head. The average of these four scans is calculated and the result is presented with normative parameters.
\nThe RNFL thickness profile at the optic disc head is the circular RNFL thickness with a diameter of 3.45 mm, which is the central optic disc and not the center of the scan itself. Ultimately, cases where the optic disc is decentralized do not affect the measurements. The RNFL thickness map is exhibited at the lower right area and the areas that are measured to be thin have a darker color while areas that are measured to be thick have a lighter color (Figure 5).
\nRNFL scan in RTVue.
In the lower right section, there is the thickness profile. Here, the RNFL thickness profile is charted temporally, superiorly, nasally, inferiorly and temporally again, in that order, beginning from around the optic disc. This thickness profile is charted as a black line by being superimposed on normative data (so that values within the normal range remain in the green-shaded area, while values outside of the normal range remain in the red-shaded area). The RNFL and the optic disc head parameters are located at the left section.
\nThe RNFL 3.45 protocol identifies the RNFL thickness of the peripapillary area by performing circular scans with a diameter of 3.45 mm around the optic disc. What is important here is the sum of four 1024-A scans performed in 0.15 s, that is, the data of 4096 scans in total.
\nThe RNFL output is divided into three sections. In the first section, regional RNFL thickness results are demonstrated with basal RNFL values and RNFL values of each subsequent check. The second section demonstrates the comparative TSNIT chart of RNFL, which is defined by a double hump pattern. The third section includes the value chart for average, superior and inferior RNFL. In addition, it illustrates the scans for each follow-up as a table including the changes between the basal scan and the last scan calculated in microns.
\nThe GCC scan has provided new parameters for the diagnosis of glaucoma. The nerve fiber layer (NFL), the ganglion cell layer and the inner plexiform layer (IPL) make up the GCC in the macular area. Today, more emphasis is placed on GCC rather than the thickness of the whole retina in the diagnosis of glaucoma [44]. In studies regarding this issue, it has been shown that glaucoma mostly thins the nerve fibers, the ganglion cells and the IPL; and the inner nuclear layer at an intermediate level and that it does not affect the outer layers [44]. The GCC study is quite useful for the early diagnosis of glaucoma and the determination of the disease’s progression, since the loss of ganglion cells occur before the visual pathway lesions and thinning of the nerve fibers [13]. RTVue, by having a mapping protocol of macular ganglion cell complex, exhibits a positive value in detecting glaucoma.
\nThe GCC thickness is defined as the distance consisting of three inner retinal layers (nerve fiber layer, ganglion cell layer and the inner plexiform layer) beginning from the inner limiting membrane and ending at the inner plexiform layer. (Figure 6) All three layers are affected in glaucoma [44].
\nAnatomy of ganglion cell complex (GCC).
When the ganglion cells die, the ganglion cell layer gets thinner and when the axon nerve fiber layer which is a part of this cell is damaged, the nerve fiber layer gets thinner. The dendrites of the same cell are located at the inner plexiform layer and as this layer is affected, the inner plexiform layer gets thinner. So, the GCC scan measures the thickness of each of these three layers which are affected by the glaucoma [46].
\nAnother advantage of the GCC thickness analysis is the macula’s inclusion of the 50% of the ganglion cells in the retina. However, NFL is very thin in the macula and since NFLs change places to form a foveal cup there are none of them in the foveola. In the perifoveal region, the NFL is very thin but the ganglion cell layer and the IPL are much thicker [47, 48].
\nThe scan includes 12 vertical lines and 1 horizontal line with a length of 7 mm. These lines are placed 0.5 mm away from each other and are focused on the temporal of the 1 mm fovea so that they include as many ganglion cells as possible. With this scan, the thickness map and the abnormal changes in the inner retina can be demonstrated.
\nThe deviation map illustrates the deviations of normal values for different ages and races that are available in the normative database. The significance map reports the findings for the patient by comparing them with the normal values in the normative database on the basis of race. Red, yellow and green colors are used to note the differences in the follow-ups. It demonstrates the significance level or the statistical significance of the deviation when compared with a normal value. In short, the significance map demonstrates how significant the difference is compared to the normal value.
\nAnother parameter here is the focal loss volume (FLV), which gives us the significant loss of GCC numerically. FLV is the sum of the significant loss of GCC topography, in terms of volume and is expressed as a percentage. At the same time, FLV is the most sensitive parameter which provides the difference between normal eyes and glaucomatous eyes (it is more sensitive than the GCC thickness parameters).
\nAs it can be seen, while RTVue provides an excellent assessment of the ganglion cell layer it also allows a comparison to be made with the normal values, based on age and race. In follow-ups, progression analysis by RTVue compares the RNFL thickness measurements and the GCC map over time and thus, determines whether statistically significant changes have occurred or not [1, 26, 49].
\nThe GCC progression report displays a total of four scans at the same time for both eyes, one of which is basal and the remaining three are for follow-ups. The output is divided into four sections. The first three sections are the GCC thickness map, the deviation map and the significance map. The GCC thickness map is the one coded with colors indicating the GCC thickness of the macular region. The deviation map is the one coded with colors indicating the loss percentages that the device determined according to the normal values based on the normative database. The significance map is the one demonstrating the statistically significant changes in comparison to the normal values by coding them in green, yellow and red colors. Finally, the fourth section includes the average, superior and inferior GCC chart. In this scan, the GCC thickness of the lower and upper hemisphere of the entire retina is scanned by excluding the foveal ring. Scan data are presented as changes between the basal scan and the last scan, calculated in microns.
\nThe normative database of RTVue OCT is the largest OCT normative database. As mentioned earlier, these databases allow to distinguish between normal cases and pathological ones. In this database, there are a total of 1600 eyes, 600 of which are from the USA and 1000 of which are from around the world. The data allow us to compare the measurements of the patients with measurements of other patients in the same age group. In the display coded with colors, green (normal), yellow (doubtful) and red (abnormal) are used.
\nIt must be noted that comparisons with normative databases are only for statistical purposes and there may be normal people with values that are outside the normal range.
\nHeidelberg Spectral Domain OCT (Spectralis, Heidelberg Engineering, Dossenheim, Germany) is an OCT device with a high scanning speed and axial resolution, allowing better reproducibility for image acquisition compared to time-domain OCT (TD-OCT) [31]. It is possible to obtain a very high-quality optic disc head image and perform peripapillary RNFL thickness analysis with this device.
\nIn scans performed circularly, the scanned areas are automatically divided into sections while the RNFL thickness is measured and compared with the values in the normative database.
\nThe OCT output in this device displays the peripapillary RNFL thickness classification by six standard pie charts:
Temporal (T)
Temporal Superior (TS)
Temporal Inferior (TI)
Nasal (N)
Nasal Superior (NS)
Nasal Inferior (NI)
In the ring which is in the middle of the pie chart, the average of the circular scan (G) is provided.
\nThe chart in the lower right corner of the window demonstrates the RNFL thickness profile that has been measured through the circular scan and its comparison with the normal ranges. The black curve represents the RNFL thickness of the patient. In both charts, three colors are available where green represents the normal RNFL thickness, yellow represents the limit value and red represents the abnormal RNFL thickness (Figure 7).
\nRNFL thickness map in Heidelberg.
On top of the output, the optic disc head scan and the real scan image of the optic disc head surroundings are provided, while the scanned image corresponding to the RNFL thickness chart is provided on the right side.
\nHeidelberg spectral OCT obtains the changes in RNFL through time by using a special software formula and uses them for monitoring the patient. This software displays the rate of difference between the average measured thickness values for each section and the normal thickness values as a chart of change. Thanks to these software, changes that occur in the RNFL profile or the deterioration that occurs in the thickness over time can be detected at an early stage [50, 51].
\nThere are 201 individuals registered in the normative database of this device, all of whom are Caucasian. Ages of these individuals range from 18 to 78, and 111 of them are male while 90 are female. The criteria for these people to be included in the database are naturally, their lack of a glaucoma history and the fact that they have normal intraocular pressure, visual field and optic disc appearance. The results have been organized as a normative database.
\nA new software called Posterior Pole Analysis is offered by the Heidelberg spectral OCT [33, 52]. Thickness of the entire posterior pole retina can be measured through this software. The posterior pole is scanned point by point, and the thickness asymmetry between the two eyes and the intraocular hemispheres are analyzed. Furthermore, the GCC loss is also assessed and findings for glaucoma at an early stage are analyzed through this software [53, 54].
\nOCT output for the analysis provides two basic maps. The first one is the map of hemisphere asymmetry while the second one is the map of RNFL thickness. The map of hemisphere asymmetry is in the form a grid where the average thicknesses of the upper and lower hemisphere are compared. Here, the squares that vertically have the same distance from the axe between the fovea and the optic disc are compared. While the squares in the upper half of the grid represent the differences between the RNFL thickness values in the superior and inferior regions, squares in the lower half represent the differences between the RNFL thickness values in the inferior and superior regions. If the difference between these values is zero or a positive value, the colored area looks white. If the area is dark gray or black, this refers to a local asymmetry in terms of RNFL thickness values.
\nIn the literature, there are several studies evaluating the diagnostic ability of abovementioned devices with some minor differences in the results [1, 2, 6, 10, 16, 17, 18, 19, 20, 21, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41].
\nLeung et al. reported that, in Spectralis, the global thickness parameter had the largest area under curve (AUC) in eyes with severe glaucoma [34]. Leite et al. reported that in Spectralis, superior quadrant RNFL followed by global RNFL, had the largest AUC and in Cirrus, global thickness was the parameter that has the largest AUC, with superior and inferior RNFL quadrants being the second and the third [54]. Park et al. and Leung et al. reported similar results with inferior, average and superior quadrant RNFL’s having the best diagnostic performance for device Cirrus as Sehi et al. [29, 30, 34].
\nIn their study, Leite et al. also showed that the diagnostic ability of all three devices for the nasal and temporal quadrants for glaucoma diagnosis was lower than the results received from the other quadrants [54]. This finding may be associated with the optic nerve damage profile in the early glaucoma where inferior and superior quadrants damaged earlier than in the nasal and temporal quadrants.
\nAlthough all these three devices represent difference in axial resolution and in time of acquisition, the final diagnostic performance for detection of glaucomatous defect generally reported to be similar.
\nDifferent results may of course be obtained due to different clinical settings, race differences, age and the severity of the disease.
\nIn conclusion, since glaucoma is a condition that shows variations over time, it is crucial that it should be closely monitored. Especially, the change of the RNFL thickness values and the values of variation for the first and last exam of the patient must be analyzed carefully.
\nNone.
\nNo conflict of interest.
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