Computational NMR Spectroscopy of Transition‐Metal/Nitroimidazole Complexes: Theoretical Investigation of Potential Radiosensitizers

Abstract

The computed chemical shifts of transition-metal complexes with dimetridazole (= 1,2-dimethyl-5-nitro-1H-imidazole; 1), a prototypical nitro-imidazole-based radiosensitizer, are reported at the GIAO-BP86 and -B3LYP levels for BP86/ECP1-optimized geometries. These complexes comprise [MCl 2 (1) 2 ] (M= Zn, Pd, Pt), [RuCl 2 (DMSO) 2 (1) 2 ], and [Rh 2 (O 2 CMe) 4 (1) 2 ]. Available d( 1 H) and d( 15 N) values, and Dd( 1 H) and Dd( 15 N) coordination shifts are well-reproduced theoretically, provided solvation and relativistic effects are taken into account by means of a polarizable continuum model and suitable methods including spin-orbit (SO) coupling, respectively. These effects are particularly important for the metal-coordinated N-atom, where the contributions from solvation and relativity can affect d( 15 N) and Dd( 15 N) values up to 10 -20 ppm. The 195 Pt chemical shifts of cis-and trans-[PtCl 2 (1) 2 ] are well-reproduced using the zero-order regular approximation including SO coupling (ZORA-SO). Predictions are reported for 99 Ru and 103 Rh chemical shifts, which suggest that these metal centers could be used as additional, sensitive NMR probes in their complexes with nitro-imidazoles.

Computational Insight into 103Rh Chemical Shift–Structure Correlations in Rhodium Bis(phosphine) Complexes

“…To probe the generality of this trend linking shifts and Rh−P distances, we analyzed even more subtle variations of the ligands. Inspired by the substituting pattern in complexes 6 and 7, the substituents in para position of the aryl groups of 6 were varied by OH (21), F (22), Cl (23), and CF 3 (24). These groups (including H and CH 3 ) can be described using Hammett σ p constants, 61 which are usually related to inductive effects.…”

“…49 The BP86 functional, employed for most of the previous optimizations of small and medium-sized Rh complexes (see references [16][17][18][19][20][21][22], is expected to be less accurate for the present set of bulky ligands, because the lack of dispersion in this functional is expected to produce overly long Rh-ligand bond distances. While such overestimated distances may still be acceptable to compute refined energies (see …”

“…In this regard, computational techniques based on density functional theory (DFT) have been successfully applied to reproduce 103 Rh chemical shifts, among other transition metals. , First computational studies on 103 Rh nuclei were devoted to organometallic compounds which span a sizable chemical shift range of ca. 3600 ppm. , The scope of this methodology has been extended to species containing phosphines, , N-donors, and alkene ligands, as well as imidazole-based radiosensitizers . Other complexes including indacenyl and porphyrin derivatives have also been analyzed.…”

“…This particular combination of levels has performed well in previous computations of 103 Rh chemical shifts. 16,[18][19][20][21][22]44 In order to obtain the corresponding chemical shifts from the magnetic shieldings, a reference is needed. Due to the lack of a suitable compound, ζ(standard) has been evaluated as the intercepts at δ = 0 of the ζ(calc) vs. δ(expt) linear regressions involving complexes 1-7 ( Figure 1) together with several species which cover a wide range of the 103 Rh chemical shift window (see Figure S1 in Supporting Information).…”

“…16,17 The scope of this methodology has been extended to species containing phosphines, 18,19 N-donor, 20 and alkene ligands, 21 as well as imidazole-based radiosensitizers. 22 Other complexes including indacenyl 23 and porphyrin 24 derivatives have also been analyzed.…”