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

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 as their photo-physical properties are dependent on the surrounding environment. This makes it possible to differentiate between different environments and as a result, allows for identification of abnormalities in DNA. 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 Tamm–Dancoff approximation (TDA) and the resolution of identity (RI) approximations provide a significant increase in speed for time-dependent density functional theory (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 density functional theory (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. The largest source of uncertainty stems from the exchange-correlation functional used in the TD-DFT calculation, where we obtain good results with PBE0 based on PBEh-3c structures.