Matched Pair
Definition: Substrate and chiral reagent/catalyst whose stereochemical preferences reinforce each other.
Context: Delivers higher selectivity than mismatched combinations.
Example: (S)-substrate with (S)-auxiliary.
Related Terms: Mismatched Pair, Double Stereodifferentiation.
Reference: Seebach, Angew. Chem. (1979).
Memory of Chirality
Definition: Retention of stereochemical information through achiral or planar intermediates via conformational constraints.
Context: Enables net stereospecificity where racemization might be expected.
Example: Acylium ion cyclizations retaining chirality.
Related Terms: Stereomutation, Enantiospecificity.
Reference: Houk, Angew. Chem. (2001).
Meso Compound
Definition: An achiral molecule with stereocenters and an internal plane/center of symmetry.
Context: No net optical activity, important in planning stereoselective routes.
Example: Meso-tartaric acid.
Related Terms: Symmetry, Diastereomer.
Reference: Eliel & Wilen (1994).
Meso-
Definition: A molecule containing stereocenters but overall achiral due to an internal plane or center of symmetry.
Context: Meso compounds are optically inactive even though they contain chiral atoms.
Example: Meso-tartaric acid.
Related Terms: Achiral; Symmetry; Diastereomer.
Reference: Eliel & Wilen (1994).
Mirror Bias
Definition: A systematic preference, assumption, or neglect arising from treating mirror-image stereoisomers as functionally equivalent when they are not.
Context: Mirror bias often manifests as an implicit assumption that enantiomers behave similarly in biological systems, leading to underestimation of differences in potency, toxicity, metabolism, or signaling. Historically, mirror bias contributed to delayed recognition of enantioselective drug effects.
Example: Assuming a racemic drug's clinical profile reflects both enantiomers equally, despite one being pharmacologically dominant or toxic.
Related Terms: Chiral Neglect; Eutomer; Distomer; Stereo-pharmacology; Stereo-Sloppy
Reference: Hutt, A. J.; Caldwell, J. The importance of stereochemistry in drug action and disposition. Pharmacology & Therapeutics, 29, 245-263 (1985).
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 ignoring enantiomeric differences leads to systemic scientific error - a direct conceptual root of mirror bias.
Misassignment of Configuration
Definition: The incorrect determination, description, or reporting of the absolute or relative stereochemical configuration of a molecule, stereogenic center, axis, or element.
Context: Misassignment of configuration can arise from incorrect application of CIP rules, misinterpretation of spectroscopic or crystallographic data, inappropriate use of chiroptical methods, or confusion between nomenclature systems (e.g., R/S vs D/L vs d/l). In pharmaceutical and medicinal chemistry, such errors can propagate through literature, patents, regulatory submissions, and clinical interpretation, leading to flawed structure-activity relationships, incorrect biological conclusions, or costly redevelopment.
Example: Assigning an alcohol as (R) based solely on optical rotation without corroborating evidence, later corrected by X-ray crystallography or VCD analysis showing the (S) configuration.
Related Terms: Absolute Configuration; Relative Configuration; CIP Rules; Stereochemical Assignment; Chiral Literacy; Stereo-Sloppy.
Reference: IUPAC. Compendium of Chemical Terminology (IUPAC Gold Book). 2nd Edition, 1997 (updated 2019).
Harada, N.; Nakanishi, K. Circular Dichroism Spectroscopy-Exciton Coupling in Organic Stereochemistry. Accounts of Chemical Research, 5, 257-263 (1972).
Mismatched Pair
Definition: Substrate and chiral reagent/catalyst with opposing preferences.
Context: Reduces stereoselectivity; addressed by switching catalyst or substrate.
Example: (S)-substrate with (R)-auxiliary.
Related Terms: Matched Pair, Stereoselectivity.
Reference: Evans, JACS (1981).
Molar Rotation (Φ)
Definition: Specific rotation multiplied by molar mass.
Context: Allows comparison of chiroptical responses across compounds.
Example: Molar rotation trends within homologous series.
Related Terms: Specific Rotation, Optical Activity.
Reference: Barron, Molecular Light Scattering (2004).
Molecular Imprinting
Definition: Template-directed polymerization producing cavities complementary to a target enantiomer.
Context: Creates synthetic receptors for separations and sensing.
Example: Imprinted polymers for S-propranolol.
Related Terms: Chiral Recognition, CSP.
Reference: Sellergren, Chem. Rev. (2000).
Mosher’s Method
Definition: Use of MTPA esters/amides to assign absolute configuration by Δδ patterns.
Context: Gold-standard for alcohols and amines in small-molecule analysis.
Example: Δδ analysis of secondary alcohols.
Related Terms: CDA, NMR.
Reference: Dale & Mosher, JACS (1973).