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

TL;DR

This paper evaluates computational methods for accurately predicting the UV-Vis absorption spectra of platinum complexes used as DNA probes, emphasizing the importance of functional choice and approximations for efficient and reliable spectral calculations.

Contribution

It benchmarks various computational approaches, recommending specific functionals and approximations for accurate and efficient UV-Vis spectra prediction of platinum-based DNA probes.

Findings

Range-separated hybrids improve spectral prediction accuracy.

TDA and RI approximations significantly speed up calculations with minimal accuracy loss.

PBEh-3c offers a good balance between computational efficiency and accuracy.

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.