Ground and excited state properties of photoactive platinum(iv) diazido complexes: Theoretical considerations

Abstract

Recently synthesized by the group of Sadler, the platinum(IV) diazido complexes [Pt(N(3))(2)(OH)(2)(L')(L'')] (L' and L'' are N-donor ligands) have potential to be used as photoactivatable metallodrugs in cancer chemotherapy. In the present study optimized structures and UV-Vis electronic spectra of trans,trans,trans- and cis,trans,cis-[Pt(N(3))(2)(OH)(2)(NH(3))(2)] (1t and 1c, respectively) as well as cis,trans,cis-[Pt(N(3))(2)(OH)(2)(L)(2)] (L = NH(3), NH(2)CH(3), NF(3), PH(3), PF(3), H(2)O, CO, OH(-), CN(-), py, imid; 2c-11c) and cis,trans-[Pt(N(3))(2)(OH)(2)(bpy)] (12c) complexes were predicted using density functional theory (DFT). The ground state electronic structures of all complexes were analyzed with the help of the natural bond orbital analysis (NBO). The electronic spectra of 1c and 1t were computed using time-dependent density functional theory (TDDFT) with five different density functionals and the ab initio CASSCF/CASPT2 method (for the five lowest energy transitions). The best agreement with available experiments was found in the case of the long-range corrected ωB97X functional. The electronic transitions were characterized by the analysis of the natural transition orbitals (NTO). The low-lying excited singlet states of 1t and 1c have significant azide-to-platinum(IV) charge-transfer character (LMCT). Geometry optimization of the three lowest singlet excited states performed using TDDFT results in the simultaneous dissociation of two azide ligands with the formation of the azidyl radicals N(3)˙ and photoreduction of Pt(IV) to Pt(II). Variation of the ligand L does not strongly affect the nature and the relative energies of the low-lying states. It is shown that the replacement of the OH(-) groups in 1c by OPh(-) ligands results in the red shift of the intense N(3)(-)→Pt LMCT band and the appearance of transitions with significant intensity in the visible region of the spectrum. The dissociative nature of the low-lying unoccupied orbitals remains unaffected. These theoretical results may suggest new experimental routes for the improvement of the photochemical activity of Pt(IV) diazido complexes.

HOMO–LUMO energy gap control in platinum(ii) biphenyl complexes containing 2,2′-bipyridine ligands

“…17,26,33 The mechanism of axial coordination to Ni(II) porphyrins upon excitation from singlet ground to triplet excited states in the presence of pyridinic ligands has also been investigated. 36,37 The photophysical properties of Ru(II), 17,38 Fe(II), 39 and Re(I) complexes 16,40 have been investigated to provide spectral assignments and detailed interpretation of electronic transitions. 36,37 The photophysical properties of Ru(II), 17,38 Fe(II), 39 and Re(I) complexes 16,40 have been investigated to provide spectral assignments and detailed interpretation of electronic transitions.…”

Effects of light-activated diazido-PtIVcomplexes on cancer cellsin vitro

“…Salassa et al [26] rationalized the photosubstitutions at Pt IV of N − 3 and NH 3 to occur for 2 from either singlet and triplet excited states, but a mechanism for Pt IV reduction could not be identified. Recently, Sokolv & Schaefer [29] proposed that the dissociation of two azido ligands from 2 might occur simultaneously with the formation of the azidyl radicals (N of azidyl radicals [14]. Likewise, the analysis of atomic charges and electronic configuration of the pyridine complexes 4-6 showed that in the lowest-lying triplet geometry, the trans azides are both less negatively charged, whereas the Pt centre is less positively charged [23,27,28].…”

“…Recently, DFT and time-dependent DFT calculations have been used to help understand the photochemistry of cytotoxic diazido-Pt IV complexes [26][27][28][29]. Salassa et al [26] rationalized the photosubstitutions at Pt IV of N − 3 and NH 3 to occur for 2 from either singlet and triplet excited states, but a mechanism for Pt IV reduction could not be identified.…”

“…These theoretical methods have been used to predict with good accuracy the UV/vis electronic absorption spectra of complexes 1 [26,29], 2 [29], 4 [23], 5 [28] and 6 [27]. Interestingly, for complex 6, the calculated low-intensity transitions in the blue region of the visible spectrum (λ = 414 nm) might account for the photoactivity induced by blue light [27].…”

Prediction of 195Pt NMR of photoactivable diazido‐ and azine‐Pt(IV) anticancer agents by DFT computational protocols

“…Photoactivable diazido‐Pt IV complexes represent an interesting class of potential anticancer agents that can be selectively activated by light and kill cells by a mechanism different to the anticancer drug cisplatin . Recently, DFT and time‐dependent DFT calculations were carried out to help understand the photochemistry of cytotoxic diazido‐Pt IV complexes . These theoretical methods have been used to predict with good accuracy the UV/vis electronic absorption spectra of the diazido‐Pt IV complexes.…”