Models for the interpretation of the action and metabolism of different drugs using FTIR matrix-isolation spectroscopy

NADIA S. VILLAR; A. LORENA PICONE; ROSANA M. ROMANO

Buenos Aires

Workshop; International Workshop on Infrared Spectroscopy Applied to Biological and Biomimetic Systems:From the Isolated Molecule to the Cell; 2007

Drugs such as ibuprofen, flurbiprofen, ketoprofen, are metabolized to coenzyme A (CoA) thioesters by acyl-CoA synthetases.1 The present work is part of a general project aimed to the study of simple models for the interpretation of the action and metabolism of drugs containing a carboxylic acid group and the coenzyme A (CoA-SH) using FTIR matrix-isolation spectroscopy. In this context interactions between carboxylic acids and methanethiol, and also methanol for comparison proposes, were investigated. Gaseous mixtures in different proportions were diluted with Ar, and then deposited on a CsI window cooled to 10 K by means of a Displex closed-cycle refrigerator (SHI-APD Cryogenics, model DE-202) using the pulse deposition technique. IR spectra of each matrix sample were recorded at resolutions of 0.5 cm-1 and 0.125 cm-1, with 256 scans, using a Nexus Nicolet instrument equipped with either an MCTB or a DTGS detector (for the ranges 4000-400 cm-1 or 600-180 cm-1, respectively). The IR matrix spectra present clear indication of the formation of a molecular complex between the carboxylic acid molecule and methanethiol or methanol, through several new absorptions that appear only in the spectra of the mixtures. The structures of the molecular complexes were studied using the B3LYP/6-311+G* approximation. For example, in the case of the interactions between propionic acid and methanol, three structures were found as energy minima, for which no imaginary frequencies occur. The most stable one presents two H-bond interactions: the acidic H interacts with the O of the methanol, while the carboxylic O interacts with the H of the alcohol group. The calculated shifts of the IR absorptions are in good agreement with the experimental ones. The most relevant features of the spectra are (experimental/theoretical values in cm-1): Än(OH)ac. prop.: -374.8 / -400.8, Än(OH)methanol.: -85.1 / -167.9, Än(CO)ac. prop.: 67.2 / 77.7, Än(C=O)ac. prop.: -34.7 / -47.9, Än(CO) methanol.: 3.2 / 8.1.