Chiral safety of the biosphere as a biophysical problem

The biosphere with its inherent chiral asymmetry fixed in the process of biological evolution at the level of L-amino acids and D-hydrocarbons and some other biologically active compounds of biogenic origin is under strong pressure of chiral substances produced by chemical, pharmaceutical, and other branches of industry and agriculture. Effective use of enantiomers is accompanied by toxic and even mutagenic effects of their mirror-image enantiomorphs. Only small amounts of products are tested for chiral purity; there is no system of global biosphere monitoring as well as no common standards of permissible concenrations. The investigation of the molecular basis of chiral stereospecificity of enzymes and cell receptors is of great interest from the point of view of fundamental biophysics. On the other hand, the development of chiral-selective sensors for environmental monitoring is important from the viewpoint of applied biophysics.     

Novel enantioselective fluorescent sensors for tartrate anion based on acridinezswsxa

Novel chiral fluorescence sensors L‐1 and D‐1 incorporating N‐Boc‐protected alanine and acridine moieties were synthesized. The recognition ability of the sensors was studied by fluorescence titration, ¹H NMR spectroscopy and density functional theory (DFT) calculations. The sensors exhibited good enantioselective fluorescent sensing ability toward enantiomers of tartrate anion for the selected carboxylate anions and formed 1: 1 complexes by multiple hydrogen bonding interactions.     

Syntheses and highly enantioselective fluorescent recognition of α-aminocarboxylic acid anions using chiral oxacalix[2]arene[2]bisbinaphthes

The triazine-based bisbinaphthyl crown ethers oxacalix[2]arene[2]bisbinaphthes R-1, R-2, R-3 and S-1, S-2, S-3 were synthesized. The interactions of these compounds with various α-aminocarboxylic acid anions were studied. The crown ethers were found to carry out highly enantioselective fluorescent recognition of α-aminocarboxylic acid anions. It is observed that within a certain concentration range, one enantiomer of the chiral α-aminocarboxylic acid anions can increase the fluorescence intensity of the crown ethers by fivefold to sixfold, whereas the other enantiomer scarcely enhances the fluorescence. Such unusually high enantioselective responses make these crown ethers very attractive as fluorescent sensors in determining the enantiomeric composition of α-aminocarboxylic acid anions.     

A New Biosensor for Chiral Recognition Using Goat and Rabbit Serum Albumin Self‐Assembled Quartz Crystal Microbalance

Quartz crystal microbalance (QCM) biosensor was used for the chiral recognition of five pairs of enantiomers by using goat serum albumin (GSA) and rabbit serum albumin (RbSA) as chiral selectors. Serum albumin (SA) was immobilized on the QCM through the self‐assembled monolayer technique, and the surface concentration of GSA and RbSA were 8.8 × 10^?12 mol cm^?2 and 1.2 × 10^?11 mol cm^?2, respectively. The QCM biosensors showed excellent sensitivity and selectivity. Meanwhile, the chiral recognition of SA sensors was quite species dependent. There were differences between GSA and RbSA sensors in the ability and the preference of chiral recognition. To R,S‐1,2,3,4‐tetrahydro‐1‐naphthylamine (R,S‐1‐TNA), R,S‐1‐(4‐methoxyphenyl)ethylamine (R,S‐4‐MPEA), and R,S‐1‐(3‐methoxyphenyl)ethylamine (R,S‐3‐MPEA), the preference of the stereoselective SA‐drug binding of the two kinds of SA sensors were consistent. However, to R,S‐2‐octanol (R, S‐2‐OT) and R,S‐methyl lactate (R,S‐MEL), the two kinds of SA sensors had opposite chiral recognition preference. Moreover, the interactions of SA and the five pairs of enantiomers have been further investigated through ultraviolet (UV) and fluorescent (FL) spectra. The UV/FL results were in accordance with the consequence of QCM. Chirality 24:804–809, 2012. © 2012 Wiley Periodicals, Inc.     

Performance of brush-type HPLC chiral stationary phases with tertiary amide in the connecting tether

The replacement of the N-H hydrogen of the secondary amide-tethered Pirkle-concept N-(3,5-dinitrobenzoyl)-L-leucine derived chiral stationary phase with various pi-basic or aliphatic groups improved the chiral discrimination ability of new chiral stationary phases, based on the leucine- or alanine-derived chiral selector, for the enantiomers of various racemic neutral analytes with amide functional groups. Retention times decreased while separation and resolution factors increased, thus proving the role of pi-donor aromatic unit as an electron-rich shield in the front of a silica surface. In general, chiral stationary phase (CSP) 5 with the 3,5-dimethylphenyl unit showed best performance, while CSP 3, with phenyl unit, and CSP 7, with 1-naphthyl unit in the tertiary amide connecting tether, were less efficient.     

Chiroptical property tuning of supramolecular assemblies in polymer matrices

Chiroptical materials have received much attention in diverse fields for applications such as displays, sensors, smart memory devices, and catalysis. Here, we develop a simple fabrication method for polymer films with tunable chiroptical properties using small amounts of self-assembling fluorescent dye as an additive. Both the circular dichroism and circularly polarized luminescence signals of the film can be tuned between positive and negative values by thermal treatment. The chiroptical properties can be varied by slight changes in the orientation of chiral pyrene moieties in self-assembled nanofibril networks.     

Resolution of the enantiomers of various alpha-substituted ornithine and lysine analogs by high-performance liquid chromatography with chiral eluant and by gas chromatography on Chirasil-Val

A reversed-phase high-performance liquid chromatography method, with L-proline and copper as chiral mobile phase, is described for the enantiomeric resolution of various alpha-substituted ornithine and lysine analogs. Although ornithine gives no separation with the chiral eluant used, excellent resolutions are obtained for various alpha-alkyl-, alpha-halogenomethyl-, alpha-vinyl-, and alpha-ethynyl-substituted ornithines. Similar separations are also observed for the dehydroornithine and lysine analogs. Gas chromatography on a chiral stationary phase, Chirasil-Val, allows the resolution of the ornithine and lysine analogs after derivatization into the monofluoroacyl derivatives of their corresponding lactams. No resolution or only a poor resolution is obtained by GC on Chirasil-Val for the dehydroornithine analogs as their di-N-perfluoroacyl alkyl esters. The chiral eluant HPLC procedure is easily scaled up for the semipreparative resolution of several ornithine analogs, i.e., alpha-fluoromethylornithine, alpha-difluoromethylornithine, alpha-chlorofluoromethylornithine, and alpha-fluoromethyldehydroornithine, which are known as potent ornithine decarboxylase inhibitors in vitro and in vivo.     

Rapid screening of enzymes for the enzymatic hydrolysis of chiral esters in drug discovery

Thirty-five enzymes were rapidly screened for their ability to selectively hydrolyze chiral esters to their corresponding carboxylic acids for the efficient generation of chiral intermediates in drug discovery. Optimization of the enzymatic reactions at various incubation times was performed using a robotic liquid handler. Enantiomeric pairs of chiral esters and carboxylic acids were then analyzed simultaneously by chiral GC/MS in a single analysis. This analytical approach is particularly useful for compounds that do not possess a conjugated chromophore or are volatile and difficult to analyze by chiral HPLC/UV or HPLC/MS. The resulting data was used to determine enantiomeric excesses and percent conversions to the desired enantiomer of the carboxylic acid for the selection of efficient enzymes for bioconversions in drug discovery in a pharmaceutical company.     

Determination of optical purity of 3,5-dimethoxybenzoyl-leucine diethylamide by chiral chromatography and 1H and 13C NMR spectroscopy

(R)-N-3,5-dinitrobenzoyl (DNB) leucine derived chiral selector was used as an HPLC chiral stationary phase for the resolution of various racemic amino acids derivatives. In this study, determination of optical purity of an amino acid derivative was performed by chiral high performance liquid chromatography and 1H and 13C NMR spectroscopy by using the DNB leucine derived chiral selector. The accuracy and precision of each optical purity value are calculated and the data are compared to each other.     

Separation of drug enantiomers by liquid chromatography and capillary electrophoresis, using immobilized proteins as chiral selectors

Proteins display interesting chiral discrimination properties owing to multiple possibilities of intermolecular interactions with chiral compounds. This review deals with proteins which have been used as immobilized chiral selectors for the enantioseparation of drugs in liquid chromatography and capillary electrophoresis. The main procedures allowing the immobilization of proteins onto matrices, such as silica and zirconia particles, membranes and capillaries are first presented. Then the factors affecting the enantioseparation of drugs in liquid chromatography, using various protein-based chiral stationary phases (CSPs), are reviewed and discussed. Last, chiral separations already achieved using immobilized protein selectors in affinity capillary electrochromatography (ACEC) are presented and compared in terms of efficiency, stability and reproducibility.     

Nanostructured material-based optical and electrochemical detection of amoxicillin antibiotic

The penicillin derivative amoxicillin (AMX) plays an important role in treating various types of infections caused by bacteria. However, excessive use of AMX may have negative health effects. Therefore, it is of utmost importance to detect and quantify the AMX in pharmaceutical drugs, biological fluids, and environmental samples with high sensitivity. Therefore, this review article provides valuable and up-to-date information on nanostructured material-based optical and electrochemical sensors to detect AMX in various biological and chemical samples. The role of using different nanostructured materials on the performance of important optical sensors such as colorimetric sensors, fluorescence sensors, surface-enhanced Raman scattering sensors, chemiluminescence/electroluminescence sensors, optical immunosensors, optical fibre-based sensors, and several important electrochemical sensors based on different electrode types have been discussed. Moreover, nanocomposites, polymer, and MXenes-based electrochemical sensors have also been discussed, in which such materials are being used to further enhance the sensitivity of these sensors. Furthermore, nanocomposite-based photo-electrochemical sensors and the market availability of biosensors including AMX have also been discussed briefly. Finally, the conclusion, challenges, and future perspectives of the above-mentioned sensing techniques for AMX detection are presented.     

Electrosynthesis of imprinted polyacrylamide membranes for the stereospecific L-histidine sensor and its characterization by AC impedance spectroscopy and piezoelectric quartz crystal technique

L-histidine/D-histidine-imprinted membranes have been synthesized by electropolymerizing acrylamide onto Au electrodes or Au-coated quartz crystal electrodes in the presence of L-histidine/D-histidine. AC impedance spectroscopy and piezoelectric quartz crystal (PQC) technique were employed to verify the template effect of the membranes. The selectively rebinding of the enantiomers of histidine by their respective imprinted polymer membranes was confirmed. The result may lead to the construction of biomimetic sensors for the stereospecific determination of L-histidine and the chiral separation of histidine.     

Apple juice and red wine induced mirror-image circular dichroism in quantum dots

Juices, wines, and extracts from plants contain high concentrations of various chiral compounds such as carboxylic acids or sugars. Several prior studies reported the synthesis of metallic and semiconducting nanoparticles relying on components of complex biological solutions. Herein, we present preparation of chiral CdS and CdSe quantum dots (QDs) using apple juice and red wine via phase transfer ligand exchange. Although both apple juice and red wine contain a complex mixture of chiral and achiral compounds, we have successfully used them for selective induction of predicted chiroptical properties and confirmed L-malic acid from the apple juice and L-tartaric acid from the red wine as the chiral inducers. This work illustrates the capability of using complex mixtures to construct chiral QDs with desired chiroptical properties as well as potential of QDs to selectively report a chiral molecule in a complex chiral mixture without the need for elaborate chiral recognition system.     

Utilization of an Enantioselective Surface Plasmon Resonance Electrode for the Selection of the Best C70 Fullerene as Chiral Selector for the Enantioanalysis of L-Cysteine

Abstract

Two novel enantioselective surface plasmon resonance (SPR) sensors based on self-assembled monolayer of (5-6)-fullerene-C₇₀ and diethyl (1,2-methanofullerene C₇₀)-71-71-dicarboxylate as chiral selectors are proposed. Binding assay, apparent affinity constant, and apparent dissociation binding constant have been used to analyze and study the enantioselectivity of C₇₀ fullerene-octadecanethiol film for L-cysteine which was chosen as model analyte. The apparent affinity constant for the complex formed by L-cysteine with (5-6)-fullerene-C₇₀ and diethyl (1,2-methanofullerene C₇₀)-71-71-dicarboxylate films were 1 × 10¹⁰ L/mol, and 6.7 × 10⁸ L/mol, respectively. Accordingly, the chiral selector of choice will be (5-6)-fullerene-C₇₀. No binding was recorded between any of the tested C₇₀ fullerenes and D-cysteine, this proving the enantioselectivity of the proposed SPR sensors.     

Design and development of genetically encoded fluorescent sensors to monitor intracellular chemical and physical parameters

Over the past decades many researchers have made major contributions towards the development of genetically encoded (GE) fluorescent sensors derived from fluorescent proteins. GE sensors are now used to study biological phenomena by facilitating the measurement of biochemical behaviors at various scales, ranging from single molecules to single cells or even whole animals. Here, we review the historical development of GE fluorescent sensors and report on their current status. We specifically focus on the development strategies of the GE sensors used for measuring pH, ion concentrations (e.g., chloride and calcium), redox indicators, membrane potential, temperature, pressure, and molecular crowding. We demonstrate that these fluroescent protein-based sensors have a shared history of concepts and development strategies, and we highlight the most original concepts used to date. We believe that the understanding and application of these various concepts will pave the road for the development of future GE sensors and lead to new breakthroughs in bioimaging.     

A comparison of LC and SFC for cellulose- and amylose-derived chiral stationary phases

This paper presents a systematic comparison of liquid chromatography (LC) and supercritical fluid chromatography (SFC) for Chiralcel OD and Chiralpak AD chiral stationary phases (CSPs), performed using various chiral compounds having a known or potential pharmaceutical activity. The chiral recognition mechanisms involved in LC and SFC for the enantiomeric separation of β-blockers have been studied more particularly. As a general rule, it appears that the presence of polar functions, like primary or secondary hydroxyl or amine functions, may result in marked discrepancies in selectivity between LC and SFC. This result is peculiar to cellulose- and amylose-derived CSPs, for which the interactions involved in chiral recognition mechanism are not always well balanced, contrary to what happens for independent CSPs. In the case of chiral resolution of polar solutes or polymer-type CSPs, the analyst should try both the LC and SFC techniques to be able to choose the more stereoselective one. © 1995 Wiley-Liss, Inc.     

Sensor heavy metal from natural resources for a green environment: A review relation between synthesis method and luminescence properties of carbon dots

Carbon dots (CDs) are 10-nm nanomaterial classes as excellent candidates in various applications: physics, biology, chemistry, and food science due to high stable biocompatibility and high surface expansive. CDs produced from natural materials have received wide attention due to their unique benefits, easy availabilities, sufficient costs, and harmless to the ecosystem. The various properties of CDs can be obtained from various synthesis methods: hydrothermal, microwave-assisted, and pyrolysis. The CDs have shown enormous potential in metal particle detection, colorimetric sensors, electrochemical sensors, and pesticide sensors. This review provides systematic information on a synthesis method based on natural resources and the application to the environmental sensors for supporting the clean environment. We hope this review will be useful as a reference source in providing the guidance or roadmap for new researchers to develop new strategies in increasing luminescence properties CDs for multi detection of heavy metals in the environment.     

Manipulation of chiral resolution for isoxazoline-based IIb/IIIa receptor antagonists using various mobile phase additives in subcritical fluid chromatography

Subcritical fluid chromatography (SubFC) using a carbon dioxide-methanol mobile phase is used for the chiral resolution of IIb/IIIa receptor antagonist enantiomers. The chiral resolution of three analogs, each containing two chiral centers, is optimized using various mobile phase additives. The effects that acidic, basic, and neutral additives have on retention, efficiency, and resolution are examined. The additive that gives the best resolution was found to be dependent upon the functionality and charge of the chiral analyte. For charged analytes, additives that act as competing ions of the same charge as the chiral analyte dramatically improve efficiency and resolution. Resolution of neutral chiral analyte enantiomers is also greatly affected by the choice of mobile phase additive. Chirality 10:338–342, 1998. © 1998 Wiley-Liss, Inc.     

Synthesis and evaluation of two novel “mixed” chiral stationary phases deriving from tyrosine: Csps designed for the resolution of either π-acid or π-basic racemates

The synthesis and chromatographic evaluation of two novel chiral stationary phases (CSPs) deriving from (S)-tyrosine are reported. The chiral graft has been designed in order to bear both π-acid and π-basic sites, each one being connected to a distinct asymmetric centre. An intramolecular π-π interaction may take place within these CSPs, leading to an energetically favoured conformation of the chiral selector (CS). The enantiorecognition ability of these CSPs was investigated for various classes of either π-acid or π-basic racemates. It is shown that these CSPs are able to separate simultaneously π-acid and π-basic racemates. Finally, chiral recognition mechanisms and mobile phase optimization are discussed.     

Functionalization of nanostructured gold substrates with chiral chromophores for SERS applications: The case of 5‐Aza[5]helicene

Nanostructured gold thin films can be fabricated by controlled pulsed laser deposition to get efficient sensors, with uniform morphology and optimized plasmon resonance, to be employed as plasmonic substrates in surface enhanced Raman scattering spectroscopy. By attaching 5‐aza[5]helicen‐6‐yl‐6‐hexanethiol to such gold nanostructures, used in a previous work for label‐free drug sensing with biomedical purposes, we successfully prepared functionalized substrates with remarkable surface enhanced Raman scattering activity. The long‐term motivation is to develop probes for drug detection at low concentrations, where sensitivity to specific chiral targets is required.