BODIPY derivatives possess unique photophysical properties and for these reasons, they have been used in numerous fields. Among the different applications, they are used in designing chemosensors that has increased in the last years. Here, we report several strategies and examples for detecting analytes of different characteristics: cations, anions, and hazardous and pollutant neutral molecules using BODIPY core as signaling unit.
- neutral molecules
Supramolecular chemistry has become a coherent and alive body of concepts which has recently incorporated new areas of research [1, 2, 3, 4]. The “classical” supramolecular chemistry has developed basic tools and concepts such as coordination of specific substrates to receptor (recognition), chemical reactivity induced by the guests (transformation), and positional controlled changes of atoms or molecules (translocation). On the other hand, another promising area of investigation is the development of “programmed supramolecular systems,” where the recognition process is coupled with a specific action.
Among these programmed systems of supramolecular background the so-called molecular chemical sensors, where the process of recognition is adapted to a process of detection, are of wide interest. The described behavior is achieved by means of the introduction in the ligand (or reactive site) of transducing units which are capable of transmitting information on the molecular recognition process through a change in its physical properties (e.g., optical or electrochemical).
There are three classical approaches for the development of chromogenic-fluorogenic sensors:
Binding site-signaling unit approach: In this approach, the receptor should contain two different subunits kept together by means of a covalent bond. One of such subunits is responsible for the complexation process, while the other transmits the molecular recognition process . As it can be seen in Figure 1, the coordination of the guest induces a change of some properties of the signaling unit, that is, color (chromogenic chemosensors) or fluorescence (fluorescent chemosensors).
Displacement approach: This approach, as well as the former, implies the use of both, specific binding sites and signaling units. However, in this case, both subunits are not covalently linked, but forming a coordination ensemble . In these systems, the addition of a given guest to the solution that contains this “molecular ensemble” favors the displacement reaction: the coordinating unit binds the guest, while the signaling unit is released toward the solution. If this unit shows different optical properties (color or fluorescence) depending on whether it is coordinated or in solution, its release causes a change of the signal. All these systems are based on the use of molecular receptors possessing coordination sites with size and charge distribution suitable to those of the guest (Figure 2).
Chemodosimeter approach: This approach involves the use of specific chemical reactions (generally irreversible) induced by the presence of certain guests that are coupled to a change of color or fluorescent emission [7, 8]. If the reaction is irreversible, the term sensor should not be strictly used, a more appropriate term should be a chromo or fluorogenic reagent or chemodosimeter. Figure 3 shows a scheme of this approach. The ultimate idea is to take advantage of the selective reactivity that determined guests present. The use of reactions induced by determined chemical species has the advantage of presenting a high selectivity and a cumulative effect that is directly related to the concentration.
Depending on the physical property of the signaling unit that changes in the process of complexation, one can readily have systems of different types, that is, electrochemical, fluorescent, colorimetric, etc. Among the different possibilities, fluorescent and colorimetric systems are very interesting due to their high sensibility and the advantage of a possible detection of species of interest to the “naked eye.”
Among the dyes or fluorophores that can be used as signaling unit, the BODIPY core presents several advantages due to its outstanding photophysical properties such as excitation/emission wavelengths in the visible spectral region (≈500 nm), the relatively high molar absorption coefficients and fluorescence quantum yields, fluorescence lifetimes in the nanosecond range, and negligible triplet-state formation. On the other hand, they are relatively insensitive to pH and present good solubility, resistance toward self-aggregation in solution and robustness against light and chemicals [9, 10]. Moreover, the spectroscopic and photophysical profiles can be switched by introducing different electron releasing/withdrawing groups at the appropriate positions of the BODIPY core. Additionally, they usually show good biocompatibility that makes them useful for biological applications.
2. Fluoro- and chromogenic chemosensors and chemodosimeter based on the BODIPY derivatives
2.1. Sensors based on the binding site-signaling unit approach
Among the different substitutions in the BODIPY core, structures like these shown in Figure 4 have been widely used in probe design. There are two main reasons for this selection: (a) the presence of the methyl substituents at 1 and 7 positions of the BODIPY core hinders the free rotation or the phenyl group at 8 which enhances the fluorescence emission and (b) the substitution at 5 or 6 in structure (II) and (III) enlarges electronic delocalization giving rise to possible color changes after the interaction with the analyte.
Many examples of fluorescent sensors based on this type of BODIPY structures were summarized in 2012 by Boens, Leen, Dehaen . For this reason, in the present chapter, only more recent publications will be considered.
In the field of alkaline cation sensors, compounds
Complexation studies of
In relation to heavy metal cations, compound
The sensing properties of
Zinc and cadmium are both elements that play many important roles in our daily life. Zinc is the second most abundant transition metal in the human body, and it is vital for the functions of a large number of enzymes, the stabilization of DNA, gene expression, and neural signal transmission. By contrast, cadmium is a dangerous poison that harms human health and the environment. Two BODIPY-based sensors (Figure 7) able to differentiate these two cations have been described .
The photophysical properties of compound
In contrast, the signaling unit and binding site in probe
2.2. Sensors based on the displacement approach
Most of the sensors following the displacement approach are based on the complexes that in the presence of the analyte, undergoes a decomplexation process that induces strong changes in the optical properties of the system. In some cases, the fluorescence of BODIPY-based compounds is quenched when a complex with the appropriate metal ion is formed. Decomplexation induced by the analyte recovers the ligand fluorescence that can be observed. This approach allows preparing off-on fluorescent chemosensors.
In that sense, compound
Based also on Cu2+ complexes, compound
Based also on the displacement approach, two complexes able to detect the V-nerve agent mimic demeton-S have been described . Acetonitrile solutions of
The behavior of
2.3. Sensors based on the chemodosimeter approach
Due to the selectivity showed by the probes designed following the chemodosimeter approach, there are a large number of applications for detecting different species.
2.3.1. Detection of anions
Following an approach that combines the chemodosimeter and the displacement mechanism, compound
Also, in relation to detecting biothiol compound
2.3.2. Detection of neutral molecules
There are a large number of neutral compounds whose detection has been developed using BODIPY-based chemodosimeters [21, 22, 23, 24, 25, 26, 27, 28]. In this chapter, there are summarized some probes used in detecting dangerous or strongly pollutant analytes.
22.214.171.124. Nerve agents
The sensing units in these compounds were based on the 2-(2-dimethylaminophenyl)ethanol moiety. This moiety has two nucleophilic groups, a dimethylamino group and a primary alcohol (
Acetonitrile solutions of
On the other hand, the sensing unit of compound
Due to the probe structure, compounds
The chromogenic behavior of the acetonitrile solutions of probe
The different chromogenic responses observed upon the addition of DCNP and DFP to
Oximates have been used from the beginning in designing chemosensors for detecting nerve agents and their simulants. Following this idea, compound
Emission spectrum of
126.96.36.199. Pollutant gases
Nitrogen oxides are very dangerous contaminants source of severe environmental problems such as acid rain, smog formation, global warming, and ozone layer weakening. Among these compounds, NO2 is one of the most prevalent and dangerous. Due to the ubiquitous presence of this gas and its health effects, the development of selective and sensitive methods for its detection and quantification has aroused a lot of interest. Thus, compounds
The BODIPY core has been successfully used in the designing of chemosensors following the three more commonly used approaches: binding site-signaling unit, displacement, and chemodosimeter. Depending on the position of the reactive unit in the BODIPY core, chromogenic or fluorescent responses were achieved. In many cases, the analyte induced changes can be observed by the naked eye. Cations, anions, and neutral molecules can be detected in different media: organic or aqueous. The biocompatibility of many of these compounds allows their use in biological applications.
Lörh H-G, Vogtle F. Chromo- and fluoroionophores. A new class of dye reagents. Accounts of Chemical Research. 1985; 18:65-72. DOI: 10.1021/ar00111a001
Izatt RM, Pawlak K, Bradshaw JS, Bruening RL. Thermodynamic and kinetic data for macrocycle interactions with cations and anions. Chemical Reviews. 1991; 91:1721-2085. DOI: 10.1021/cr00008a003
Bisel RA, de Silva AP, Gunaratne HQN, Lynch PL, Maguire GEM, Sandanayake KRAS. Molecular fluorescent signalling with ‘fluor-spacer-receptor’ systems: Approaches to sensing and switching devices viasupramolecular photophysics. Chemical Society Reviews. 1992; 21:187-195. DOI: 10.1039/CS9922100187
An H, Bradshaw J, Izatt RM, Yan Z. Bis- and oligo(benzocrown ether)s. Chemical Reviews. 1994; 94:939-391. DOI: 10.1021/cr00028a005
Fabbrizzi L, Poggi A. Sensors and switches from supramolecular chemistry. Chemical Society Reviews. 1995; 22:197-201. DOI: 10.1039/CS9952400197
Wiskur SL, Aït-Haddou H, Lavigne JJ, Anslyn EV. Teaching old indicators new tricks. Accounts of Chemical Research. 2001; 34:963-972. DOI: 10.1021/ar9600796
Chae M-Y, Czarnik AW. Fluorometric chemodosimetry. Mercury(II) and silver(I) indication in water via enhanced fluorescence signaling. Journal of the American Chemical Society. 1992; 114:9704-9705. DOI: 10.1021/ja00050a085
Dujols V, Ford F, Czarnik AW. A long-wavelength fluorescent chemodosimeter selective for Cu(II) ion in water. Journal of the American Chemical Society. 1997; 119:7386-7387. DOI: 10.1021/ja971221g
Ziessel R, Ulrich G, Harriman A. The chemistry of bodipy: A new El Doradofor fluorescence tools. New Journal of Chemistry. 2007; 31:496-501. DOI: 10.1039/B617972J
Ulrich G, Ziessel R, Harriman A. The chemistry of fluorescent bodipy dyes: Versatility unsurpassed. Angewandte Chemie, International Edition. 2008; 47:1184-1201. DOI: 10.1002/anie.200702070
Boens N, Leen V, Dehaen W. Fluorescent indicators based on BODIPY. Chemical Society Reviews. 2012; 41:1130-1172. DOI: 10.1039/C1CS15132K
Depauw A, Kumar N, Ha-Thi M-H, Leray I. Calixarene-based fluorescent sensors for cesium cations containing BODIPY fluorophore. The Journal of Physical Chemistry. A. 2015; 119:6065-6073. DOI: 10.1021/jp5120288
Madhu S, Sharma DK, Basu SK, Jadhav S, Chowdhury A, Ravikanth M. Sensing Hg(II) in vitroand in vivousing a benzimidazole substituted BODIPY. Inorganic Chemistry. 2013; 52:11136-11145. DOI: 10.1021/ic401365x
He H, Ng DKP. Differential detection of Zn2+ and Cd2+ ions by BODIPY-based fluorescent sensors. Chemistry, an Asian Journal. 2013; 8:1441-1446. DOI: org/10.1002/asia.201300183
Barba-Bon A, Calabuig L, Costero AM, Gil S, Martínez-Máñez R, Sancenón F. Off–on BODIPY-based chemosensors for selective detection of Al3+ and Cr3+ versusFe3+ in aqueous media. RSC Advances. 2014; 4:8962-8965. DOI: 10.1039/C3RA46845C
Juárez LA, Barba-Bon A, Costero AM, Martínez-Máñez R, Sancenón F, Parra M, Gaviña P, Terencio MC, Alcaraz MJ. A boron dipyrromethene (BODIPY)-based CuII-bipyridine complex for highly selective no detection. Chemistry–A European Journal. 2015; 21:15486-15490. DOI: 10.1002/chem.201502191
More AB, Mula S, Thakare S, Chakraborty S, Ray AK, Sekar N, Chattopadhyay S. An acac-BODIPY dye as a reversible “ON-OFF-ON” fluorescent sensor for Cu2+ and S2− ions based on displacement approach. Journal of Luminescence. 2017; 190:476-484. DOI: 10.1016/j.jlumin.2017.06.005
Barba-Bon A, Costero AM, Gil S, Sancenón F, Martínez-Máñez R. Chromo-fluorogenic BODIPY-complexes for selective detection of V-type nerve agent surrogates. Chemical Communications. 2014; 50:13289-13291. DOI: 10.1039/C4CC05945J
Tsay OG, Lee KM, Churchill DG. Selective and competitive cysteine chemosensing: Resettable fluorescent “turn on” aqueous detection via Cu2+ displacement and salicylaldimine hydrolysis. New Journal of Chemistry. 2012; 36:1949-1952. DOI: 10.1039/c2nj40387k
Zhang J, Ji X, Ren H, Zhou J, Chen Z, Dong X, Zhao W. Meso-heteroaryl BODIPY dyes as dual-responsive fluorescent probes for discrimination of Cys from Hcy and GSH. Sensors and Actuators B: Chemical. 2018; 260:861-869. DOI: org/10.1016/j.snb.2018.01.016
Lin Q, Gurskos JJ, Buccella D. Bright, red emitting fluorescent sensor for intracellular imaging of Mg2+. Organic & Biomolecular Chemistry. 2016; 14:11381-11388. DOI: 10.1039/c6ob02177h
Zhang C, Han Z, Wang M, Yang Z, Ran X, He W. A new BOPDUPY-derived ratiometric sensor with internal change transfer (ICT) effect: Colorimetric/fluorometric sensing of Ag+. Dalton Transactions. 2018; 47:2285-2291. DOI: 10.1039/c7dt04345g
Üçüncü M, Karakus E, Emrullahoglu M. A BODIPY-based fluorescent probe for ratiometric detection of gold ions: Utilization of Z-enynol as the reactive unit. ChemComm. 2016; 52:8247-8250. DOI: 10.1039/c6cc04100k
Ashokkumar P, Weisshoff H, Kraus W, Rurack K. Test-strip-based fluorometric detection of fluoride in aqueous media with BODIPY-linked hydrogen-bonding receptor. Angewandte Chemie, International Edition. 2014; 53:2225-2229. DOI: 10.1002/anie.201307848
Ali F, Aute S, Sreedharan S, Nila HA, Saeed HK, Smythe CG, Thomas JA, Das A. Tracking HOCl concentrations across cellular organelles in real time using a super resolution microscopy probe. ChemComm. 2018; 54:1849-1852. DOI: 10.1039/c7cc09433g
Li B, He Z, Zhou H, Zhan H, Li W, Cheng T. Reaction based colorimetric fluorescence probes for selective detection of hydrazine. Dyes and Pigments. 2017; 146:300-304. DOI: org/10.1016/j.dyepig.2017.07.023
Sedgwick AC, Chepman RSL, Gardine JE, Peacock LR, Kim G, Yoon J, Bull SD, James TD. A bodipy based hydroxylamine sensor. ChemComm. 2017; 53:10441-10445. DOI: 10.1039/c7cc05872a
Purdey MS, McLennan HJ, Sutton-McDowall ML, Drumm DW, Zhang X, Capon PK, Heng S, Thompson JG, Abell AD. Biological hydrogen presoide detection with ary boronate and benzyl BODIPY-based fluorescent probes. Sensors and Actuators B: Chemical. 2019; 262:750-757. DOI: org/10.1016/j.snb.2018.01.198
Madhu S, Bandela S, Ravikanth M. BODIPY based fluorescent chemodosimeter for explosive picric acid in aqueous media and rapid detection in the solid state. RSC Advances. 2014; 4:7120-7123. DOI: 10.1039/c3ra46565a
Gotor R, Costero AM, Gaviña P, Gil S. Ratiometric double channel borondipyrromethene based chemodosimeter for the selective detection of nerve agent mimics. Dyes and Pigments. 2014; 108:76-83. DOI: org/10.1016/j.dyepig.2014.04.011
Gotor R, Gaviña P, Ochando LE, Chulvi K, Lorente A, Martínez-Máñez R, Costero AM. BODIPY dyes functionalized with 2-(2-dimethylaminophenyl)ethanol moieties as selective OFF–ON fluorescent chemodosimeters for the nerve agent mimics DCNP and DFP. RSC Advances. 2014; 4:15975-15982. DOI: 10.1039/C4RA00710G
Barba-Bon A, Costero AM, Gil S, Harriman A, Sancenon F. Highly selective detection of nerve-agent simulants with BODIPY dyes. Chemistry–A European Journal. 2014; 20:6339-6634. DOI: org/10.1002/chem.201304475
Barba-Bon A, Costero AM, Gil S, Martínez-Máñez R, Sancenón F. Selective chromo-fluorogenic detection of DFP (a Sarin and Soman mimic) and DCNP (a Tabun mimic) with a unique probe based on a boron dipyrromethene (BODIPY) dye. Organic & Biomolecular Chemistry. 2014; 12:8745-8751. DOI: 10.1039/C4OB01299B
Jang YJ, Tsay OG, Murale DP, Jeong JA, Segev A, Churchill DG. Novel and selective detection of Tabun mímics. ChemComm. 2014; 50:7531-7534. DOI: 10.1039/c4cc02689f
Sayar M, Karakus E, Gener T, Yildiz B, Yildiz UH, Emrullahoglu M. A BODIPY-Based fluorescent probe to visually detect phosgene: Toward the development of a handheld phosgene detector. Chemistry - A European Journal. 2018; 24:3136-3140. DOI: 10.1002/chem.2017056 13
Juárez LA, Costero AM, Sancenón F, Martínez-Máñez R, Parra M, Gaviña P. A new simple chromo-fluorogenic probe for NO2 detection in air. Chemistry–A European Journal. 2015; 21:8720-8722. DOI: 10.1002/chem.201500608
Juárez LA, Costero AM, Parra M, Gil S, Martínez-Máñez R. A new chromo-fluorogenic probe based on BODIPY for NO2 detection in air. Chemical Communications. 2015; 51:1725-1727. DOI: 10.1039/C4CC08654F