The collective vibrational modes of dihydropyridine in nifedipine studied by terahertz spectroscopy

Abstract

Cardiovascular pharmaceuticals have drawn huge attention in drug development. Nifedipine (NFD) is an important member of calcium channel blockers (CCB) with the structural characteristic of dihydropyridine (DHP), but the binding mechanism to its target remains an open question. Even though several analytical techniques have been used for structural characterizations, the information of collective vibrational behavior is still lacking. In this work, we use terahertz (THz) spectroscopy to investigate the spectral fingerprints of NFD, and quantitatively evaluate the temperature-induced frequency shifts. Combined with quantum chemical calculations, each THz fingerprint is attributed to specific collective vibrational modes. The collective vibrations of DHP are mainly distributed below 2.5 THz, which provides complementary information to understand the behavior of rigid DHP ring. The rotation of methyl group and the wagging of nitrophenyl group are widely distributed in the range of 1.0-4.0 THz, which is helpful for the conformational recognition between NFD and target molecule. THz spectroscopy is demonstrated to be suitable for characterizing the collective vibrational modes of DHP and elucidating the drug-target binding behavior from the perspective of noncovalent interactions. It has the potential to become a non-invasive technology for conformational analysis and pharmaceutical development.

Keywords: Collective vibrational modes; Dihydropyridine; Nifedipine; Quantum chemical calculations; Spectral fingerprints; Terahertz time-domain spectroscopy.