CBS Reduction
Definition: Corey–Bakshi–Shibata borane reduction of ketones using chiral oxazaborolidines.
Context: Reliable route to enantioenriched alcohols.
Example: CBS reduction of aryl ketones.
Related Terms: Asymmetric Catalysis, Reduction.
Reference: Corey, JACS (1987).
Chelation Control
Definition: Metal coordination overrides Felkin preferences in carbonyl additions.
Context: Explains opposite selectivity in presence of Lewis acids or metals.
Example: Addition to α-alkoxy aldehydes with Mg2+.
Related Terms: Cram’s Rule, Felkin–Anh.
Reference: Reetz, Angew. Chem. (1974).
Chiral
Definition: A geometric property of a molecule or object that is not superimposable on its mirror image.
Context: Chirality is foundational in stereochemistry, determining whether enantiomers exist and influencing pharmacological activity.
Example: Hands are chiral objects; lactic acid has R- and S-enantiomers.
Related Terms: Enantiomer; Chiral Center; Stereoisomer.
Reference: IUPAC. Compendium of Chemical Terminology (IUPAC Gold Book), 2nd Edition, 1997 (updated 2019).
Chiral Auxiliary
Definition: Temporarily attached chiral unit to control stereochemistry of a transformation.
Context: Delivers high selectivity; removed to give target enantioenriched product.
Example: Evans oxazolidinone auxiliaries.
Related Terms: Chiral Pool, Asymmetric Catalysis.
Reference: Evans, JACS (1981).
Chiral Awareness
Definition: The explicit recognition and incorporation of chirality in thinking, language, experimental design, data handling, modeling, regulation, and decision-making. Chiral awareness involves treating stereoisomers-especially enantiomers and diastereomers-as distinct chemical entities with potentially different properties, activities, safety profiles, and biological outcomes.
Example: Correct specification of stereochemical configuration in names, drawings, and databases; Clear communication of stereochemistry in teaching, papers, labels, and reports; Discrimination between stereoisomers in experiments, analysis, and modelling consideration of stereoselective pharmacology, metabolism, and toxicity; Avoidance of "stereochemical collapse" in AI/ML representations and informatics.
Related terms: Chiral-aware (adjectival form); Chiral Literacy; Chiral Intelligence; Chiral Bias; Stereo-blindness; Stereo-sloppy.
References: Eliel, E. L., & Wilen, S. H. Stereochemistry of organic compounds. New York: Wiley (1994);
Ariens, E. J. Stereochemistry, a basis for sophisticated nonsense in pharmacokinetics and clinical pharmacology. European Journal of Clinical Pharmacology, 26, 663-668 (1984);
Smith, S. W. Chiral toxicology: It's the same thing... only different. Toxicological Sciences, 110(1), 4-30 (2009).
Chiral Bioequivalence
Definition: Demonstration that enantiomer exposure (AUC, Cmax) is equivalent between products.
Context: Regulatory expectation for racemates and single-enantiomer generics.
Example: Bioequivalence of racemic vs reformulated enantiomer products.
Related Terms: Bioequivalence, FDA Chiral Policy.
Reference: FDA Guidance (2017); FDA 1992 Policy.
Chiral CE (Capillary Electrophoresis)
Definition: Electrophoretic separation with chiral selectors (e.g., cyclodextrins) in the buffer.
Context: High-efficiency analytical separations for enantiomers.
Example: CE of amino acid enantiomers.
Related Terms: Chiral HPLC, CSP.
Reference: Scriba, Electrophoresis (2003).
Chiral Center
Definition: A tetrahedral atom (usually carbon) bonded to four different substituents.
Context: Creates enantiomeric pairs; critical for drug selectivity and metabolism.
Example: The α-carbon of lactic acid.
Related Terms: Stereocenter, Enantiomer.
Reference: IUPAC Gold Book.
Chiral Derivatizing Agent (CDA)
Definition: Enantiomers are converted to diastereomers by reacting with a chiral reagent to enable separation.
Context: Facilitates NMR/LC analysis when direct separation is difficult.
Example: Mosher’s acid chloride (MTPA-Cl).
Related Terms: CDA, Chiral Solvating Agent.
Reference: Mosher, JACS (1973).
Chiral Drug
Definition: A pharmaceutical compound that contains one or more chiral centers or stereogenic elements, existing as enantiomers, diastereomers, or mixtures.
Context: Regulatory and therapeutic implications are critical; one enantiomer may be active (eutomer) while the other may be inactive or harmful (distomer).
Example: Ibuprofen (sold as a racemate, though only the S-enantiomer is pharmacologically active).
Related Terms: Enantiopure; Racemate; Eutomer; Distomer; Stereo-pharmacology.
Reference: FDA. Policy Statement for the Development of New Stereoisomeric Drugs (1992).
Chiral Education
Definition: The structured teaching and learning of chirality and stereochemistry, from fundamental spatial concepts to advanced applications in synthesis, biology, and medicine.
Context: Chiral education spans undergraduate instruction, professional training, and continuing education. Modern chiral education emphasizes three-dimensional thinking, molecular visualization, biological relevance, and translational impact, particularly in medicinal chemistry and pharmaceutical sciences.
Example: Teaching stereochemistry using molecular models and real drug case studies (e.g., thalidomide, ibuprofen, citalopram) rather than only abstract projections.
Related Terms: Chiral Literacy; Stereochemistry; Medicinal Chemistry; Stereo-pharmacology, Chiral Pharmacology
Reference: Holme, T. A. Assessing conceptual understanding in stereochemistry. Journal of Chemical Education, 96, 401-410 (2019); Nicoll, G. Investigating student misconceptions in organic chemistry: Stereochemistry and representations. Journal of Chemical Education, 78, 623-627 (2001); Clement, J., & Ainsworth, S. Multiple visual representations in chemistry learning. Topics in Cognitive Science, 10, 857-874 (2018); Underwood, S. M., et al. Expert-novice differences in interpreting stereochemical representations. Journal of Chemical Education, 93, 2014-2021 (2016).
Chiral Fidelity
Definition: The degree to which stereochemical integrity is preserved throughout molecular design, synthesis, analysis, formulation, storage, and biological evaluation.
Context: Chiral fidelity reflects how well a system maintains the intended configuration or enantiomeric composition without racemization, epimerization, or atropisomer interconversion. In pharmaceutical development, high chiral fidelity is essential for reproducibility, safety, and regulatory compliance across the product lifecycle.
Example: Demonstrating that an enantiopure API retains ?99% enantiomeric excess during scale-up, formulation, and shelf-life stability studies.
Related Terms: Enantiopure; Racemization; Stereomutation; Chiral Control; Stereochemical Stability
Reference: ICH Q6A. Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and Products (1999).
Ariens, E. J., Stereochemistry, a basis for sophisticated nonsense in pharmacokinetics and clinical pharmacology, European Journal of Clinical Pharmacology, 26, 663-668 (1984).
DOI: 10.1007/BF00541922
Demonstrates how maintaining or improving enantiomeric integrity alters clinical outcomes - a practical expression of chiral fidelity.
Chiral GC (Gas Chromatography)
Definition: GC using chiral stationary phases for volatile enantiomers.
Context: Useful for small, volatile APIs and intermediates.
Example: Resolution of limonene enantiomers.
Related Terms: Chiral HPLC, CE.
Reference: Schurig & Nowotny, J. Chromatogr. A (1990).
Chiral HPLC
Definition: HPLC using chiral stationary phases to separate enantiomers.
Context: Workhorse analytical and preparative method in pharma.
Example: Separation of R/S-propranolol.
Related Terms: CSP, SFC.
Reference: Scriba, J. Chromatogr. A (2016).
Chiral Intelligence
Definition: The capacity to understand, interpret, and apply chirality-dependent information across chemical, biological, pharmacological, and regulatory domains.
Context: Chiral intelligence goes beyond recognizing stereochemical descriptors; it integrates molecular structure, biological response, metabolism, safety, and lifecycle decision-making. In pharmaceutical development, chiral intelligence underpins decisions on enantiomer selection, analytical control, regulatory strategy, and clinical risk assessment.
Example: Recognizing that only S-ibuprofen is pharmacologically active, while R-ibuprofen undergoes partial in vivo inversion, and integrating this knowledge into dosing, formulation, and regulatory justification.
Related Terms: Chiral Literacy; Stereo-pharmacology; Eudismic Ratio; Enantiopure; Chiral Drug, Stereochemistry-Aware Models; Enantiomeric Specificity.
Reference: Ariens, E. J. Stereochemistry, a basis for sophisticated nonsense in pharmacokinetics and clinical pharmacology. Medical Research Reviews, 4, 197-236 (1984); Jorner, K., Yu, E., Yoshikawa, N., Jorner, K., Aspuru-Guzik, A., et al. Stereochemistry-aware string-based molecular generation. PNAS Nexus, 4(11), pgaf329 (2025); Reymond, J.-L. Stereochemistry in chemoinformatics and artificial intelligence. Accounts of Chemical Research, 55, 2210-2220 (2022).
Chiral Inversion
Definition: In vivo conversion of one enantiomer to the other.
Context: Impacts dosing and exposure; must be characterized in PK.
Example: R-ibuprofen inverts to S-ibuprofen in humans.
Related Terms: Stereopharmacology, Metabolism.
Reference: Hutt & Caldwell, J. Pharm. Pharmacol. (1983).
Chiral Ligand
Definition: A ligand that induces asymmetry in metal-catalyzed reactions.
Context: Central in enantioselective hydrogenation and C–C bond formation.
Example: BINAP ligand.
Related Terms: Asymmetric Catalysis, Enantioselectivity.
Reference: Noyori, Angew. Chem. (1994).
Chiral Literacy
Definition: The foundational ability to read, interpret, and correctly use stereochemical language, representations, and concepts in chemistry and life sciences.
Context: Chiral literacy includes competence with R/S, E/Z, D/L, wedge-dash notation, projections (Fischer, Newman), and stereochemical terminology. It is essential for clear scientific communication, avoidance of stereochemical errors, and proper interpretation of literature, patents, and regulatory documents.
Example: Correctly distinguishing between D/L nomenclature (relative configuration) and d/l optical rotation, avoiding the common misconception that they are equivalent.
Related Terms: Chiral Education; Stereochemistry; Configuration; Stereoisomers, Stereochemical Notation; Spatial Reasoning; Asymmetric Synthesis.
Reference: Eliel, E. L., Wilen, S. H., & Mander, L. N. (1994). Stereochemistry of Organic Compounds. Wiley; Clayden, J., Greeves, N., & Warren, S. (2021). Organic Chemistry (2nd ed.). Oxford University Press; Kociok-Kohn, G. Chirality and its importance in chemistry and biology. Angewandte Chemie International Edition, 57, 10956-10958 (2018); Fallen, B., et al. Students' difficulties with chirality and stereochemical reasoning: A review. Chemistry Education Research and Practice, 21, 307-323 (2020).
Chiral Mass Spectrometry
Definition: MS technique combined with chiral derivatization or ion mobility to distinguish enantiomers.
Context: Emerging analytical tool for stereoisomers.
Example: Chiral recognition of amino acids.
Related Terms: MS, Chiral Derivatizing Agents.
Reference: Dwivedi et al., Anal Chem (2006).
Chiral Pharmacology
Definition: The study of how molecular chirality influences pharmacodynamic and pharmacokinetic behavior in biological systems.
Context: Enantiomers often differ in potency, metabolism, and toxicity. Understanding chiral pharmacology is crucial for rational drug development and regulatory approval.
Example: S-warfarin is the more potent anticoagulant enantiomer compared to R-warfarin.
Related Terms: Stereo-pharmacology; Eutomer; Distomer; Enantiomeric Excess.
Reference: Caldwell, J. (1995). Chiral pharmacology and the regulation of new drugs. Chemistry and Industry, 6, 176-179; Hutt, A. J. & Caldwell, J. "The importance of stereochemistry in drug action and disposition." Pharmacology & Therapeutics, 29(2): 245-263 (1985).
Chiral Phosphate Catalysis
Definition: Brønsted acid catalysis using BINOL-derived chiral phosphoric acids.
Context: Broad platform for enantioselective additions and rearrangements.
Example: CPA-catalyzed Mannich reactions.
Related Terms: Organocatalysis, Brønsted Acid Catalysis.
Reference: Akiyama/Terada, Chem. Rev. (2018).
Chiral Photochemistry
Definition: Use of light to induce stereocontrol via chiral catalysts, templates, or circularly polarized light.
Context: Enables unique selectivity pathways and deracemization.
Example: CPL-mediated enantioenrichment.
Related Terms: Asymmetric Catalysis, CPL.
Reference: Bach & Hehn, Angew. Chem. (2011).
Chiral Pool Synthesis
Definition: Use of abundant natural enantiopure building blocks as stereochemical sources.
Context: Efficient, scalable strategy in pharmaceutical synthesis.
Example: Use of L-amino acids to set stereochemistry.
Related Terms: Biocatalysis, Chiral Auxiliary.
Reference: Morrison & Boyd.
Chiral Recognition
Definition: Selective interaction of a host with one enantiomer over the other.
Context: Underlies chiral separations and receptor binding selectivity.
Example: Cyclodextrin inclusion complexes.
Related Terms: Molecular Imprinting, Chiral HPLC.
Reference: Wainer, Drug Discov Today (1997).
Chiral Resolution by Enzymes
Definition: Use of biocatalysts to selectively transform one enantiomer.
Context: Scalable, green alternative to chemical resolution.
Example: Lipase-catalyzed ester hydrolysis.
Related Terms: Biocatalysis, Kinetic Resolution.
Reference: Bornscheuer, Nature (2012).
Chiral SFC (Supercritical Fluid Chromatography)
Definition: Chromatography using supercritical CO2 with chiral stationary phases.
Context: Fast, green separations widely adopted for enantioresolution.
Example: Rapid enantiomer separation of β-blockers.
Related Terms: Chiral HPLC, CSP.
Reference: Berger, Supercritical Fluid Chromatography (1995).
Chiral Shift Reagent
Definition: Paramagnetic lanthanide complexes that induce differential NMR shifts for enantiomers.
Context: Legacy technique for stereochemical analysis.
Example: Eu(fod)3 added to racemates.
Related Terms: CSA, NMR.
Reference: Günther, NMR Spectroscopy (2013).
Chiral Solvating Agent (CSA)
Definition: Chiral additive forming diastereomeric complexes that resolve NMR signals.
Context: Allows ee determination without derivatization.
Example: Pirkle’s alcohols; TFAE.
Related Terms: CDA, NMR.
Reference: Pirkle, J. Org. Chem. (1967).
Chiral Stationary Phase (CSP)
Definition: Chromatographic phase containing chiral selectors (polysaccharides, cyclodextrins, Pirkle-type, proteins).
Context: Core technology for analytical and preparative enantioseparation.
Example: Cellulose tris(3,5-dimethylphenylcarbamate).
Related Terms: Chiral HPLC, SFC.
Reference: Scriba, J. Chromatogr. A (2016).
Chiral Switch
Definition: Replacing a racemic drug with its single active enantiomer.
Context: Lifecycle and safety strategy improving efficacy and dose control.
Example: Esomeprazole replacing omeprazole.
Related Terms: Eutomer, Stereopharmacology.
Reference: FDA Policy (1992).
Chiral Toxicology
Definition: Study of enantioselective toxicity and safety profiles.
Context: Eutomers and distomers can differ in adverse effects; regulators expect isomer-specific assessment.
Example: S-thalidomide vs R-thalidomide.
Related Terms: Eutomer, Distomer.
Reference: FDA Stereoisomeric Drugs Policy (1992).
Chiral-First Design
Definition: A molecular design philosophy in which chirality is considered a primary design parameter from the earliest stages of discovery, rather than an afterthought addressed during optimization or development.
Context: Chiral-first design integrates stereochemistry into target selection, ligand design, synthesis planning, and biological evaluation. This approach reduces downstream risk, avoids late-stage chiral switches, and improves alignment between chemical structure and biological function.
Example: Designing a kinase inhibitor library around a defined axial chirality scaffold instead of screening racemic mixtures and resolving later.
Related Terms: Chiral Intelligence; Stereo-pharmacology; Enantioselective Synthesis; Drug Design Strategy
Reference: Ariens, E. J., Stereochemistry, a basis for sophisticated nonsense in pharmacokinetics and clinical pharmacology, European Journal of Clinical Pharmacology, 26, 663-668, (1984)
DOI: 10.1007/BF00541922
FDA Guidance for Industry (1992) Development of New Stereoisomeric Drugs
Establishes the requirement to maintain, characterize, and justify stereochemical integrity throughout development - a direct institutional basis for chiral fidelity.
Chiral-Induced Spin Selectivity (CISS)
Definition: Phenomenon where electron spin polarization arises during transport through chiral media.
Context: Emerging relevance in bioelectronics and sensing; conceptual interest in drug–protein interactions.
Example: Spin filtering through DNA helices.
Related Terms: Helicity, Chiroptics.
Reference: Naaman & Waldeck, Annu. Rev. Phys. Chem. (2015).
Chirality
Definition: A geometric property where an object or molecule is not superimposable on its mirror image.
Context: Foundational to stereochemistry; chirality determines enantiomer formation and can alter pharmacological profiles.
Example: Hands are chiral; R- and S-lactic acid are mirror images.
Related Terms: Enantiomer, Stereocenter, Stereoisomer.
Reference: IUPAC Gold Book (2019).
CIP Rules
Definition: Priority rules to rank substituents for stereochemical assignment.
Context: Foundation for R/S and E/Z nomenclature across industry and regulation.
Example: Assigning R to lactic acid’s chiral center.
Related Terms: R/S Configuration, E/Z Isomerism.
Reference: Cahn, Ingold & Prelog, Experientia (1956).
Circular Dichroism (CD)
Definition: Difference in absorption of left vs right circularly polarized light.
Context: Key chiroptical method for absolute configuration and secondary structure.
Example: ECD of helicenes; protein far-UV CD.
Related Terms: ECD, VCD, ROA.
Reference: Kelly et al., Biochim. Biophys. Acta (2005).
Circularly Polarized Luminescence (CPL)
Definition: Difference in emission of left vs right circularly polarized light.
Context: Emerging tool for chiral luminophores and bioimaging probes.
Example: CPL of lanthanide complexes.
Related Terms: CD, g-factor.
Reference: Zinna & Di Bari, Chirality (2015).
Configuration
Definition: The fixed spatial arrangement of atoms about a stereogenic element not interconverted without bond breaking.
Context: Configuration defines absolute identity of stereoisomers and must be controlled in pharma.
Example: R vs S configuration at a chiral center.
Related Terms: Absolute Configuration, Relative Configuration.
Reference: IUPAC Gold Book.
Conformation
Definition: Different spatial arrangements generated by rotation about single bonds.
Context: Bioactive conformation often dictates receptor binding and SAR.
Example: Anti vs gauche conformers of butane.
Related Terms: Conformational Isomerism, Bioactive Conformation.
Reference: Clayden et al., Organic Chemistry (2012).
Conformational Constraint
Definition: Structural modification limiting molecular flexibility.
Context: Improves binding affinity and selectivity.
Example: Locked nucleic acids (LNAs).
Related Terms: SAR, Pharmacophore.
Reference: Silverman, Drug Design (2014).
Conformational Isomer (Conformer)
Definition: Isomers differing only by rotation about single σ-bonds without bond breaking.
Context: Conformational analysis is essential in understanding stability, reactivity, and bioactive geometry.
Example: Chair and boat forms of cyclohexane.
Related Terms: Conformer; Conformation; Eclipsed; Gauche.
Reference: Clayden, J., Greeves, N., Warren, S. & Wothers, P. Organic Chemistry. Oxford University Press, 2012.
Conformational Isomerism
Definition: Interconversion between isomers via rotation about σ-bonds.
Context: Conformational preferences control stereochemical outcomes and binding.
Example: Chair vs boat cyclohexane.
Related Terms: Conformation, Stereoelectronic Effect.
Reference: Clayden et al. (2012).
Conformer
Definition: A specific spatial arrangement of atoms in a molecule that can be interconverted by rotation about single bonds.
Context: Conformers represent energetically accessible geometries; populations depend on steric and electronic effects.
Example: Staggered and eclipsed conformations of ethane.
Related Terms: Conformational Isomer; Newman Projection; Gauche; Eclipsed.
Reference: Eliel, E. L. & Wilen, S. H. Stereochemistry of Organic Compounds. Wiley, 1994.
Conglomerate (Racemic Conglomerate)
Definition: Racemic mixture that crystallizes as separate enantiomorphic crystals.
Context: Enables preferential crystallization and Viedma ripening strategies.
Example: Sodium ammonium tartrate behavior.
Related Terms: Racemate, Viedma Ripening.
Reference: Eliel & Wilen (1994).
Cornforth Model
Definition: Predicts anti-selective substitution via antiperiplanar alignment.
Context: Used for 1,3-asymmetric induction analysis.
Example: Allylic substitutions.
Related Terms: Felkin–Anh, Zimmerman–Traxler.
Reference: Cornforth, Chem. Soc. Rev. (1971).
Cotton Effect
Definition: Characteristic sign and magnitude change in CD/ORD near an absorption band.
Context: Diagnostic for electronic transitions and stereochemical assignment.
Example: Positive/negative couplets in aromatic chromophores.
Related Terms: CD, ORD, Exciton Coupling.
Reference: Nakanishi et al. (2007).
Cram’s Rule
Definition: Predicts diastereofacial selectivity based on minimizing steric interactions.
Context: Competes with chelation control in carbonyl additions.
Example: Nucleophile addition to chiral ketones.
Related Terms: Felkin–Anh, Chelation Control.
Reference: Cram, JACS (1952).
Curtin–Hammett Principle
Definition: Product distribution is determined by transition-state energies when conformers interconvert faster than they react.
Context: Explains selectivity in conformationally flexible systems.
Example: Axial/equatorial conformers leading to different products.
Related Terms: Conformation, Kinetics.
Reference: Seeman, Chem. Rev. (1983).
Cyclodextrin CSP
Definition: Cyclodextrin-based selectors suitable for polar and volatile analytes.
Context: Common in CE and GC for small molecules.
Example: β-Cyclodextrin phases.
Related Terms: CSP, Chiral CE/GC.
Reference: Scriba (2003/2016).