Quantum chemical studies of the spectroscopic properties of the E-64 protease inhibitor

Abstract

This work presents quantum chemical studies of the thiol proteinase inhibitor E-64. Quantum mechanical full geometry optimizations are performed using different ab initio theoretical models. These range from Hartree–Fock to density-functional levels (B3LYP) using two different basis sets (6-31G and 6-31G(d)). Vibrational frequencies are calculated and compared to the experimental results. Assignment of the frequencies is made using the calculated results and a FT-IR experiment. The UV–vis spectrum is calculated using INDO/CIS calculations in the ab initio geometries obtained with HF/6-31G, B3LYP/6-31G and B3LYP/6-31G(d) and compared with our experimental results. Solvent effects are included in the theoretical absorption spectrum with a self-consistent-reaction field method. A detailed theoretical analysis of the excitation nature is given. The chromophore responsible for the characteristic transition with maximum at 200nm is identified. The chromophore is localized at the terminal amine group of the molecule suggesting that the experimental spectrum should be relatively stable with respect to possible change of conformations. Comparison between the theoretical and experimental results is also made using the crystallographic structure of E-64. Overall, the calculated and measured UV–vis absorption spectra are in excellent agreement.