Structure and Dynamics of Theophylline in D2O Investigated by 2D IR

Abstract

Theophylline is one of the xanthine derivatives. The molecular structure of theophylline is like purine (i.e., adenine and guanine), so it acts like a competitive and nonspecific ribonucleoside inhibitor. Because of this character, theophylline has been widely used as tablet pills to help asthma patients. The crystal structure of theophylline monohydride and the intermolecular interaction between theophylline and DNA/RNA sequences has been reported to improve its pharmaceutical usage. We investigated the structure and dynamics of theophylline using Fourier transform infrared (FT IR) and two-dimensional infrared (2D IR) spectroscopy to understand molecular couplings and vibrational dynamics of two carbonyl groups, which have not been studied so far. We obtained time-resolved 2D IR spectra of theophylline in D2O solution from T = 0 to T = 10 ps, with four different polarization sets. We observed cross peaks between the two C=O modes of theophylline in the 2D IR spectra, where the magnitude and sign of the cross peaks depend on the polarization of the involved IR pulses. The two modes were determined to be almost orthogonal to each other due to strong coupling. Time-dependent 2D IR spectra revealed energy transfer between the two modes and H-bond exchange between the C=O and water occurring predominantly in one of the C=O groups.