Probing NMR parameters, structure and dynamics of 5-nitroimidazole derivatives. Density functional study of prototypical radiosensitizers

Abstract

The 15N chemical shifts of metronidazole (1), secnidazole (2), nimorazole (3) and tinidazole (4), radiosensitizers based on the 5-nitroimidazole motif, are reported. A detailed computational study of 1 is presented, calling special attention to the performance of various theoretical methods in reproducing the 13C and 15N data observed in solution. The most sophisticated approach involves density functional-based Car-Parrinello molecular dynamics simulations (CPMD) of 1 in aqueous solution (BP86 level) and averaging chemical shifts over snapshots from the trajectory. In the NMR calculations for these snapshots (performed at the B3LYP level), a small number of discrete water molecules are retained, and the remaining bulk solution effects are included via a polarizable continuum model (PCM). A similarly good accord with experiment is obtained from much less involved, static geometry optimization and NMR computation of pristine 1 employing a PCM approach. Solvent effects on delta(15N), which are of the order of up to 20 ppm, are not due to changes in geometric parameters upon solvation, but arise from the direct response of the electronic wavefunction to the presence of the solvent, which can be represented by discrete molecules and/or the dielectric bulk.

99Tc NMR as a promising technique for structural investigation of biomolecules: theoretical studies on the solvent and thermal effects of phenylbenzothiazole complex

“…The resulting 13 C chemical shifts were converted to the usual TMS scale using the experimental value for benzene [ δ ( 13 C) = 128.5 ppm], and the resulting 99 Tc chemical shifts were converted using the experimental value for TcO −4 [ δ ( 99 Tc) = 0 ppm] …”

“…Cancer is an old and serious problem facing humanity, having a great and limiting influence on the quality of life and the development of many countries, besides causing many deaths . In this context, breast cancer is one of the major health problems of the western world, where more than one million new cases occur every year, mainly in women between 40 and 59 years old …”

“…In spite of the great importance of investigating the solvent and thermal effects on NMR parameters of such metal complexes of biological interest, very few studies about this subject have been reported . Actually, theoretical approaches to compute NMR parameters are now implemented in very efficient codes using computer facilities with rapidly increasing performance . Nowadays, ab initio computation of NMR parameters, such as chemical shifts or coupling constants, can be very useful to support recorded spectra and investigate structure–property relationships .…”

Exploring EPR Parameters of 99Tc Complexes for Designing New MRI Probes: Coordination Environment, Solvent, and Thermal Effects on the Spectroscopic Properties

“…Since the time-scale accessible to the atomcentered density matrix propagation (ADMP) [25] method is very restricted, no extensive equilibration is possible and care must be taken to start from reasonably well preequilibrated configuration. To this end, we first prepared a classical system through an MD simulation using the modified force field (GROMOS96) [26,27] with the GROMACS 5.1 package [28]. As usual, periodic boundary conditions (PBC) and a cutoff distance of 9.0Å were applied.…”

Berry Pseudorotation Mechanism for the Interpretation of the 19F NMR Spectrum in PF5 by Ab Initio Molecular Dynamics Simulations

“…The decrease of 19 F chemical shielding as a function of temperature has already been observed experimentally on PF 5 [10] , and theoretically for different systems. [25,26] Consequently, the determination of chemical shifts needs to use a chemical shielding reference computed using the same theoretical approach that particularly takes into account thermal effects. The 19 F shielding constants of CFCl 3 have been calculated by performing ab initio molecular dynamics on this molecular system using the same procedure as for PF 5 at 298 K. The mean shielding obtained for CFCl 3 at 298 K is 151.11 ppm, which is 6.5 ppm lower than the static reference value (157.61 ppm).…”