Computational Vibrational Spectroscopy of Hydrophilic Drug Irinotecan

Abstract

A computational study of structural and vibrational spectroscopic properties of hydrophilic drug irinotecane was carried out. Both static and dynamical approaches to the problem have been implemented. In the static ones, vibrational spectra of the title system were computed within the double harmonic approximation, diagonalizing the mass-weighted Hessian matrices. These were calculated for the minima on AM1, PM3, PM6 and B3LYP/6-31G(d,p) potential energy surfaces. Within the dynamical approach, atom-centered density matrix propagation scheme was implemented at AM1 level of theory. From the computed molecular dynamics trajectories at series of temperatures (ranging from 10 to 300 K), velocity-velocity autocorrelation function was calculated and the vibrational density of states was sequentially obtained by Fourier ransformation. Comparison with the experimental data revealed that the employed density functional level of theory exhibited remarkable performances. Of all semiempirical theoretical levels, PM6 was found to perform best, comparable to B3LYP/6-31G(d,p) when lower-frequency region is in question.