Efficient Calculation of Absorption Spectra of Platinum Complexes Used as Luminescent Probes for Cancer Detection

TL;DR

This work benchmarks methods for computing UV-Vis spectra of a Pt(II) pincer complex and finds that the largest source of uncertainty stems from the exchange-correlation functional and recommends range-separated hybrids for robust spectral predictions.

Abstract

Despite major advances in oncology, many chemotherapeutic agents still cause severe side effects that reduce quality of life, motivating new approaches for early detection and targeted elimination of cancer cells. Luminescent transition metal complexes are promising biomolecular probes, since intercalation between DNA base pairs significantly changes their luminescence. However, reliable computational protocols to predict optical properties of transition metal intercalators are limited, making accurate absorption spectra calculations essential for screening candidates. Here, we benchmark methods for computing UV-Vis spectra of a Pt(II) pincer complex. The complex is studied both in isolation and intercalated in a small DNA model, representing probes designed to target DNA-associated molecular abnormalities. We find that the largest source of uncertainty stems from the exchange-correlation functional and recommend range-separated hybrids for robust spectral predictions. The Tamm-Dancoff approximation (TDA) and the resolution of identity (RI) approximations provide significant speedups for TD-DFT with only a modest loss of accuracy. Since geometry optimization is often the dominant cost, PBEh-3c emerges as an efficient alternative to conventional DFT, introducing errors comparable to those from TDA. Tight-binding methods (GFN-xTB) offer further acceleration, but yield larger deviations in structures and UV-Vis spectra; thus, unless extensive optimization is required, PBEh-3c provides the best balance between accuracy and efficiency.

Figures (16)

• Figure 1: The isolated Pt(II) model complex ([Pt(OH)(terpy)]+) and the Pt(II) model intercalated in a double helical DNA fragment investigated in this paper. For both systems, the oxygen atoms are red, the phosphor atoms are orange, the nitrogen atoms are blue, the hydrogen atoms are white, and the carbon atoms are gray. The platinum center is also gray, but can be distinguished from the carbon atoms by its spherical shape.
• Figure 2: Overlays of the intercalated complex optimized with (a) PBE0/def2-SVP and (b) PBEh-3c, respectively, to the PBE/def2-SVP structure.
• Figure 3: Overlays of the intercalated complex optimized with (a) GFN1-xTB and (b) GFN2-xTB, respectively, overlayed on the PBE/def2-SVP structure.
• Figure 4: UV-Vis spectra calculated with the scalar relativistic PBE0/x2c-SVPall method, including perturbative SOC. The compared structures were optimized with PBE/def2-SVP (black) and PBEh-3c (red). A FWHM of 0.3 eV was used to smear the spectra.
• Figure 5: UV-Vis spectra for the intercalated structure calculated with PBE0/x2c-SVPall and perturbative SOC. The compared structures were optimized with PBE/def2-SVP in black and in red (a) GFN1-xTB and (b) GFN2-xTB. An FWHM of 0.3 eV was used to smear the spectra.