Investigating the influence of relativistic effects on absorption spectra for platinum complexes with light-activated activity against cancer cells

TL;DR

This study explores how relativistic effects influence the UV-vis absorption spectra of platinum complexes used in light-activated cancer therapy, highlighting the importance of spin-orbit coupling in accurate spectral predictions.

Contribution

It is the first to systematically analyze relativistic effects on the spectra of PACT platinum complexes using TD-DFT with various Hamiltonians, emphasizing the significance of spin-orbit coupling.

Findings

Large differences between 4c and NR spectra, especially at lower energies.

Scalar-relativistic methods can approximate intense spectral features well.

Explicit spin-orbit coupling is crucial for understanding weaker, lower-energy transitions.

Abstract

We report the first investigation of relativistic effects on the UV-vis spectra of two prototype complexes for so-called photo-activated chemotherapy (PACT), trans-trans-trans-[Pt(N3)2(OH)2(NH3)2] and cis-trans-cis-[Pt(N3)2(OH)2(NH3)2].In PACT, design of new drugs requires in-depth understanding of the photo-activation mechanisms. A first step is usually to rationalize their UV-vis spectra for which time-dependent density functional theory (TD-DFT) is an indispensable tool. We carried out TD-DFT calculations with a systematic series of non-relativistic(NR), scalar-relativistic (SR), and four-component (4c) Hamiltonians. Large differences are found between spectra calculated within 4c and NR frameworks, while the most intense features (found at higher energies below 300 nm) can be reasonably well reproduced within a SR framework. Yet the underlying transitions can be strongly influenced by spin-orbit coupling introduced in the 4c framework: while this can affect both intense and less intense transitions in the spectra, the effect is most pronounced for weaker transitions at lower energies, above 300 nm. Since the investigated complexes are activated with light of wavelengths above 300 nm, employing a method with explicit inclusion of spin-orbit coupling may be crucial to rationalize the activation mechanism. All calculations were carried out with both the CAM-B3LYP and B3LYP functionals; we generally find the former to perform best in comparison with experimental spectra.