Single-Isomer Science: The Phenomenon and Its Terminology

CNS Spectrums ◽  
2002 ◽  
Vol 7 (S1) ◽  
pp. 8-13 ◽  
Author(s):  
Joseph Gal

ABSTRACTSingle-isomer drugs are of great importance in modern therapeutics. In this article, the basics of the underlying phenomenon are explained. Some molecules are chiral, ie, their mirror image is not superposable on the original. The most common element producing molecular chirality is a chiral center, typically a carbon atom carrying four different groups. The mirror-image molecules are termed enantiomers, but the less specific terms stereoisomers and isomers are also used. A substance consisting of only one of the two enantiomers is a single enantiomer or single isomer, and the 1:1 mixture of the enantiomers is the racemic mixture or racemate. A graphical convention that conveys the three-dimensional aspects of chiral molecules drawn in two dimensions, as well as two nongraphical conventions, based on optical rotation and configuration, are used to identify enantiomers. Optical rotation is a physical property of single enantiomers and involves rotation of the plane of plane-polarized light, each pure enantiomer rotating with equal magnitude but in the opposite direction (dextro and levo). Configuration is the actual arrangement in space of the atoms of chiral molecules. Two systems of indicating configuration are in use. One employs D and L to denote the respective enantiomers, and is applicable only to α-amino acids and carbohydrates. The other is a universal system using R and S as descriptors for the two possible arrangements, respectively, of the atoms around the chiral center. Interest in chiral drugs stems from the frequently observed biological differences between enantiomers. Such enantioselectivity is the result of different interactions of the drug enantiomers with target receptors that are themselves chiral and single-enantiomeric.

CNS Spectrums ◽  
2002 ◽  
Vol 7 (S1) ◽  
pp. 14-22 ◽  
Author(s):  
Andrew J. Hutt

ABSTRACTUntil relatively recently the three-dimensional nature of drug molecules has been largely neglected, with approximately 25% of marketed drugs being mixtures of agents rather than single chemical entities. These mixtures are not combinations of drugs but mixtures of stereoisomers, generally racemates of synthetic chiral drugs. The individual enantiomers present in such mixtures frequently differ in both their pharmacodynamic and pharmacokinetic profiles as a result of stereochemical discrimination on interaction with chiral biological macromolecules (enzymes and receptors). The use of such mixtures may present problems if their adverse effects are associated with the less active stereoisomer or do not show stereoselectivity. In addition, interactions between enantiomers may occur such that the observed activity of the racemate is not simply the product of the effects of the individual enantiomers. Since the mid-1980s there has been an ongoing “racemate-versus-enantiomer” debate with the potential advantages of single-isomer products, including improved selectivity of action and potential increase in therapeutic index, being highlighted. As a result, regulatory authorities have issued guidelines for dealing with chiral molecules, and the number of single enantiomer agents presented for evaluation has increased. Racemic mixtures may still be developed but require justification such that the risk-benefit ratio may be assessed. In addition to new chemical entities, a number of “old” mixtures are being re-examined as potential single-isomer products, the chiral switches, with the potential for an improved therapeutic profile and possibly new indications. However, for the majority of agents currently marketed as mixtures, relatively little is known concerning the pharmacological or toxicological properties of the individual enantiomers.


2020 ◽  
Vol 10 (15) ◽  
pp. 5357
Author(s):  
Muhammad Shajih Zafar ◽  
Andrea Ragusa

Chiral molecules, such as amino acids and carbohydrates, are the building blocks of nature. As a consequence, most natural supramolecular structures, such as enzymes and receptors, are able to distinguish among different orientations in space of functional groups, and enantiomers of chiral drugs usually have different pharmacokinetic properties and physiological effects. In this regard, the ability to recognize a single enantiomer from a racemic mixture is of paramount importance. Alternatively, the capacity to synthetize preferentially one enantiomer over another through a catalytic process can eliminate (or at least simplify) the subsequent isolation of only one enantiomer. The advent of nanotechnology has led to noteworthy improvements in many fields, from material science to nanomedicine. Similarly, nanoparticles functionalized with chiral molecules have been exploited in several fields. In this review, we report the recent advances of the use of chiral nanoparticles grouped in four major areas, i.e., enantioselective recognition, asymmetric catalysis, biosensing, and biomedicine.


2021 ◽  
Vol 93 (13) ◽  
pp. 5403-5411
Author(s):  
Dang-Bao-An Tran ◽  
Katherine M. Manfred ◽  
Robert Peverall ◽  
Grant A. D. Ritchie

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 1145
Author(s):  
Yuan Zhao ◽  
Xuecheng Zhu ◽  
Wei Jiang ◽  
Huilin Liu ◽  
Baoguo Sun

With the rapid development of global industry and increasingly frequent product circulation, the separation and detection of chiral drugs/pesticides are becoming increasingly important. The chiral nature of substances can result in harm to the human body, and the selective endocrine-disrupting effect of drug enantiomers is caused by differential enantiospecific binding to receptors. This review is devoted to the specific recognition and resolution of chiral molecules by chromatography and membrane-based enantioseparation techniques. Chromatographic enantiomer separations with chiral stationary phase (CSP)-based columns and membrane-based enantiomer filtration are detailed. In addition, the unique properties of these chiral resolution methods have been summarized for practical applications in the chemistry, environment, biology, medicine, and food industries. We further discussed the recognition mechanism in analytical enantioseparations and analyzed recent developments and future prospects of chromatographic and membrane-based enantioseparations.


CNS Spectrums ◽  
2002 ◽  
Vol 7 (S1) ◽  
pp. 45-54 ◽  
Author(s):  
Joseph Gal

ABSTRACTIn 1992, the Food and Drug Administration (FDA) issued new guidelines governing stereoisomerism in new-drug development. The guidelines strongly encourage the development of single isomers and discourage stereoisomeric (eg, racemic) mixtures. As a result, most new chiral drugs are being developed as single enantiomers (ie, single isomers). There are three mechanisms for the identification and development of new single-isomer drugs: chiral switches (CS), chiral metashifts (CM), and new single-isomer chemical entities (NSICEs). In a CS, one of the two enantiomers of an established racemate is developed as a new drug, with the expectation that the single-isomer form has advantages over the racemic parent in terms of efficacy and/or adverse effects. Many new CS drugs are in development, eg, (S)-oxybutynin for urinary incontinence and escitalopram for depression. In a CM, a chiral metabolite of a drug is developed, in single-isomer form, as an agent with advantages over the parent. Among the current CM drugs in development are (+)-norcisapride (safer GI prokinetic agent than the racemic parent cisapride) and (S)-desmethylzopiclone (antianxiety agent, metabolite of the sedative-hypnotic zopi-clone). Many NSICEs are in development, eg, rosuvastatin as an antihypercholesterolemic, posaconazole as an antifungal, sitafloxacin as a fluoroquinolone antibacterial, pregabalin as an anticonvulsant, abarelix as an antineoplastic, etc. As in the development of any new drug, not every single-isomer candidate will reach the clinic, but there is no doubt that the move to single-isomer agents is an important step forward in the search for better and safer drugs.


2002 ◽  
Vol 16 (19) ◽  
pp. 721-726 ◽  
Author(s):  
ZHIDONG ZHANG ◽  
ZHIGUANG LI ◽  
JINGLI LIU

The temperature-dependent pitch of a cholesteric phase is studied using both molecular field theory and the two-particle cluster theory. The interacting chiral molecules (as derived by van der Meer et al.) are placed at the sites of a three-dimensional, simple cubic lattice with orientations confined to two dimensions. The equilibrium pitch as functions of temperature is calculated and numerical results are compared with those predicted by Monte Carlo computer simulation. The two-particle cluster theory, taking into account short-range correlations between molecules, yields improved values compared with molecular field theory.


Author(s):  
Indu Bhushan

Lipases are a multipurpose enzyme that holds a significant position in industrial applications due to its ability to catalyse a large number of reactions such as hydrolysis, esterification, interesterification, transesterification which makes it a potential candidate. It is also used for the separation of chiral drugs from the racemic mixture and this property of lipase is considered very important in pharmaceutical industries for the synthesis of enantiopure bioactive molecules. Assuming the tremendous importance of lipases, as stereoselective biocatalysts, in pharmaceuticals and various other commercial applications, industrial enzymologists have been forced to search for those microorganisms which are able to produce novel biocatalysts at reasonably high yield. In the present study microbial lipase was isolated from the water sample of pond at Katra, Jammu and Kashmir (India). This enzyme has shown wide specificity and higher enantioselectivity, which make it pharmaceutical important enzyme. To make it economical for industrial application, it was produced on cheap nutrient media using Response Surface Methodology and got maximum production. It was used for resolution of chiral drugs and the significant results obtained during the course of work shall have potential towards pharmaceutical industries.


Molecules ◽  
2019 ◽  
Vol 24 (6) ◽  
pp. 1007 ◽  
Author(s):  
Ankur Gogoi ◽  
Nirmal Mazumder ◽  
Surajit Konwer ◽  
Harsh Ranawat ◽  
Nai-Tzu Chen ◽  
...  

Chiral molecules are stereoselective with regard to specific biological functions. Enantiomers differ considerably in their physiological reactions with the human body. Safeguarding the quality and safety of drugs requires an efficient analytical platform by which to selectively probe chiral compounds to ensure the extraction of single enantiomers. Asymmetric synthesis is a mature approach to the production of single enantiomers; however, it is poorly suited to mass production and allows for only specific enantioselective reactions. Furthermore, it is too expensive and time-consuming for the evaluation of therapeutic drugs in the early stages of development. These limitations have prompted the development of surface-modified nanoparticles using amino acids, chiral organic ligands, or functional groups as chiral selectors applicable to a racemic mixture of chiral molecules. The fact that these combinations can be optimized in terms of sensitivity, specificity, and enantioselectivity makes them ideal for enantiomeric recognition and separation. In chiral resolution, molecules bond selectively to particle surfaces according to homochiral interactions, whereupon an enantiopure compound is extracted from the solution through a simple filtration process. In this review article, we discuss the fabrication of chiral nanoparticles and look at the ways their distinctive surface properties have been adopted in enantiomeric recognition and separation.


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