Premium
The solid‐state conformation of the topical antifungal agent O ‐naphthalen‐2‐yl N ‐methyl‐ N ‐(3‐methylphenyl)carbamothioate
Author(s) -
Ho Douglas M.,
Zdilla Michael J.
Publication year - 2018
Publication title -
acta crystallographica section c
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.304
H-Index - 17
ISSN - 2053-2296
DOI - 10.1107/s2053229618013591
Subject(s) - chemistry , stereochemistry , moiety , substituent , conformational isomerism , double bond , aryl , solid state , ligand (biochemistry) , crystallography , organic chemistry , alkyl , biochemistry , molecule , receptor
Tolnaftate, a classic antifungal compound, has been found to crystallize from 1:1 ( v / v ) acetone–water as large flat colorless needles in the centrosymmetric monoclinic space group P 2 1 / c . These crystals contain a 50:50 mixture of the (+ ap ,− sp ,+ ac ,− ac ) and (− ap ,+ sp ,− ac ,+ ac ) conformers. The bond lengths in the central CNOS unit are 1.3444 (19), 1.3556 (18) and 1.6567 (15) Å for C—N, C—O and C—S, respectively, and the CNOS and C 3 N moieties are flat and nearly coplanar with each other, consistent with the C—N bond possessing partial double‐bond character. Tolnaftate and the four most closely related N , N ‐disubstituted thiocarbamates in the Cambridge Structural Database (CSD) all exist as E ‐conformational isomers in the solid state. Among these five compounds, tolnaftate is the only one in which the N ‐tolyl moiety is positioned trans to the S atom, i.e. the N ‐aryl substituent in each of the other compounds is positioned cis to their respective S atom. Notably, and more importantly, our experimental X‐ray structure is unlike all prior theoretical models available for tolnaftate. The implication, either directly or indirectly, is that some of those theoretical models used in earlier studies to explain the spectroscopic properties of tolnaftate and to suggest which protein–ligand interactions are responsible for the binding of tolnaftate to squalene epoxidase are either inappropriate or structurally unreasonable, i.e. the results and conclusions from those prior studies are in need of critical reassessment.