title: In search of the mutual relationship between the structure, solid-state spectroscopy and molecular dynamics in selected calcium channel blockers.
abstract: Three isostructural 1,4-dihydropyridines (DHPs), namely, nifedipine, nitrendipine and nimodipine were selected to characterize their structure, intermolecular interactions and molecular dynamics. The studied samples were analyzed using powder X-ray diffraction (XRD), neutron (INS) and infrared spectroscopy (FT-IR) as well as solid-state nuclear magnetic resonance (NMR), where each technique was supported by the state-of-the-art theoretical calculations for solid-state. By combining multiple experimental techniques with advanced theoretical calculations we were able to shed light on the mutual relation between the structure, stabilizing intermolecular interactions and their spectral response. For the first time, unambiguous computationally-supported assignment of the most prominent spectral features in DHPs is presented to give a valuable support for polymorph screening and drug control. Molecular motions were interpreted in details, revealing that a dynamic reservoir of each compound is dominated by intra-molecular reorientations of methyl groups and large-amplitude oscillations in terminal chains. Our study successfully validates the realm of applicability of first-principles solid-state calculations in search of the mutual relation between the structure and spectroscopy in this important class of drugs. Such approach gives a first necessary step to gather combined structure-dynamics data on functionalized DHPs, which are of importance to better understand crystallization and binding tendency. The NMR relaxation experiments reveal that nitro groups significantly hinder the reorientation of methyl rotors and provide the first evidence of low-temperature methyl-group tunneling in DHPs, an intriguing quantum-effect which is to be further explored.
authors.affiliation: Department of Radiospectroscopy, Faculty of Physics, Adam Mickiewicz University, Umultowska 85, 61-614 Poznan, Poland; Frank Laboratory of Neutron Physics, Joint Institute for Nuclear Research, 141980 Dubna, Russian Federation. Electronic address: kacper.druzbicki@amu.edu.pl.
authors.forename: Kacper
authors.initials: K
authors.lastname: Drużbicki
authors.affiliation: Department of Radiospectroscopy, Faculty of Physics, Adam Mickiewicz University, Umultowska 85, 61-614 Poznan, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Pajzderska
authors.affiliation: Department of Radiospectroscopy, Faculty of Physics, Adam Mickiewicz University, Umultowska 85, 61-614 Poznan, Poland; NanoBioMedical Center, Adam Mickiewicz University, Umultowska 85, 61-614 Poznan, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Kiwilsza
authors.affiliation: NanoBioMedical Center, Adam Mickiewicz University, Umultowska 85, 61-614 Poznan, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Jenczyk
authors.affiliation: Department of Radiospectroscopy, Faculty of Physics, Adam Mickiewicz University, Umultowska 85, 61-614 Poznan, Poland; Frank Laboratory of Neutron Physics, Joint Institute for Nuclear Research, 141980 Dubna, Russian Federation.
authors.forename: Dorota
authors.initials: D
authors.lastname: Chudoba
authors.affiliation: NanoBioMedical Center, Adam Mickiewicz University, Umultowska 85, 61-614 Poznan, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Jarek
authors.affiliation: Department of Inorganic and Analytical Chemistry, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznan, Poland.
authors.forename: Jadwiga
authors.initials: J
authors.lastname: Mielcarek
authors.affiliation: Department of Radiospectroscopy, Faculty of Physics, Adam Mickiewicz University, Umultowska 85, 61-614 Poznan, Poland; NanoBioMedical Center, Adam Mickiewicz University, Umultowska 85, 61-614 Poznan, Poland.
authors.forename: Jan
authors.initials: J
authors.lastname: Wąsicki
mesh_terms: D002121:Calcium Channel Blockers / Q000737:chemistry*; D003460:Crystallization / Q000379:methods; D004095:Dihydropyridines / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D056004:Molecular Dynamics Simulation; D009543:Nifedipine / Q000737:chemistry; D009553:Nimodipine / Q000737:chemistry; D009568:Nitrendipine / Q000737:chemistry; D011789:Quantum Theory; D013055:Spectrophotometry, Infrared / Q000379:methods; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D009553:Nimodipine; C038806:1,4-dihydropyridine; D009568:Nitrendipine; D009543:Nifedipine
keywords: 1,4-Dihydropyridines; Molecular dynamics; Optical and neutron vibrational spectroscopy; Plane-Wave Dispersion-Corrected DFT; Solid-state NMR