Computational protocol for predicting the nitrogen-15 NMR chemical shift in platinum(II) complexes

Cancer represents a major global health challenge, with 50% of chemotherapy treatments involving platinum-based drugs that exhibit side effects such as cytotoxicity. Nuclear Magnetic Resonance (NMR) serves as a tool in the discovery of new anticancer drug candidates. In this study, computational protocols were developed to predict N-15 NMR chemical shifts (δ¹⁵N) in Pt(II) complexes. Complex geometries were optimized at DFT-Functional/LANL2TZ(f)(Pt)/def2-SVP(ligands)/IEF-PCM(UFF) level. NMR calculations to obtain the shielding constant (σ) were performed using 56 different DFT functionals at the non-relativistic GIAO-Functional-DFT/NMR-DKH/IEF-PCM(UFF) level in Gaussian 16 Rev. C.01, while ZORA calculations were carried out at GIAO-Functional-DFT-SC-ZORA/NMR-ZORA/C-PCM level in ORCA 6.1.1. The δ¹⁵N calculation was performed using δ¹⁵N = σ_ref – σ_calc. The best-performing protocols were used to construct linear correlation between σ¹⁵N_calc and δ¹⁵N_expt. The lowest mean relative deviations (MRD) were obtained with GIAO-B1B95/NMR-DKH/IEF-PCM(UFF)//B3LYP/LANL2TZ(f)/def2-SVP/IEF-PCM(UFF) (δ¹⁵N_calc = -0.8390σ¹⁵N_calc - 203.8) and GIAO-SC-ZORA-PBE0/NMR-ZORA/C-PCM(UFF)//PBE/LANL2TZ(f)/def2-SVP/IEF-PCM(UFF) (δ¹⁵N_calc = -0.8986σ¹⁵N_calc - 195.25), 4.8% and 4.3%, respectively.