Cocaine Hydrochloride Structure in Solution Revealed by Three Chiroptical Methods

• Published in: Chemphyschem Vol. 18; no. 16; pp. 2258 - 2265
• Main Authors: Fagan, Patrik, Kocourková, Lucie, Tatarkovič, Michal, Králík, František, Kuchař, Martin, Setnička, Vladimír, Bouř, Petr
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 18-08-2017
• Subjects: analytical methods; Aqueous solutions; Banded structure; Biological activity; circular dichroism; Cocaine; Crystal structure; density functional calculations; Density functional theory; Deuteration; Dichroism; Optical activity; Raman spectra; Raman spectroscopy; Scattering; Spectroscopic analysis; structure elucidation; density functional calculations; circular dichroism; structure elucidation; Raman spectroscopy; analytical methods
• ISSN: 1439-4235; 1439-7641
• DOI: 10.1002/cphc.201700452

Structure and flexibility of natural compounds determine their biological activity. In the present study, electronic circular dichroism (ECD), vibrational circular dichroism (VCD), and Raman optical activity (ROA) spectra of cocaine hydrochloride in aqueous solutions were measured and related to the structure with the aid of density functional theory (DFT) computations. Additional measurements in deuterated environment made assignment of vibrational bands easier. The results suggest that the prevalent cocaine conformation in solution differs from that adopted in hydrochloride crystal. The spectroscopic results and computational analysis are consistent with X‐ray structures of known cocaine‐receptor complexes, in which the compound adopts a variety of conformations. All three kinds of chiroptical spectra exhibited significantly greater conformational sensitivity than unpolarized absorption or Raman scattering. The ROA technique provided the largest number of well‐resolved bands, bearing rich structural information.
Sensitive structures: The solution structure of biologically relevant molecules is important for their biological activity. For cocaine, a combination of chiral spectroscopies is used to establish the prevalent conformer, which turns out to be different to that in crystals. The spectral analysis is greatly enhanced by computational modeling.