Can Expanded Bacteriochlorins Act as Photosensitizers in Photodynamic Therapy? Good News from Density Functional Theory Computations.

Gloria Mazzone,Nino Russo,Tiziana Marino,Marta Alberto,Bruna De Simone

doi:10.3390/molecules21030288

Abstract

The main photophysical properties of a series of expanded bacteriochlorins, recently synthetized, have been investigated by means of DFT and TD-DFT methods. Absorption spectra computed with different exchange-correlation functionals, B3LYP, M06 and ωB97XD, have been compared with the experimental ones. In good agreement, all the considered systems show a maximum absorption wavelength that falls in the therapeutic window (600–800 nm). The obtained singlet-triplet energy gaps are large enough to ensure the production of cytotoxic singlet molecular oxygen. The computed spin-orbit matrix elements suggest a good probability of intersystem spin-crossing between singlet and triplet excited states, since they result to be higher than those computed for 5,10,15,20-tetrakis-(m-hydroxyphenyl)chlorin (Foscan©) already used in the photodynamic therapy (PDT) protocol. Because of the investigated properties, these expanded bacteriochlorins can be proposed as PDT agents.

Highlights

Photodynamic therapy (PDT) is a minimally invasive therapeutic intervention currently used for the treatment of a variety of cancers and non-oncological disorders [1,2,3]
The present study provides a screening of the expanded bacteriochlorins properties which can help to select the study provides a screening of the expanded bacteriochlorins properties which can help to select the best candidate as photodynamic therapy (PDT) agent
Absorption spectra have been obtained as vertical electronic excitations from the minima of the ground-state structures by using time-dependent density functional response theory (TD-DFT) [52]

Summary

Introduction

Photodynamic therapy (PDT) is a minimally invasive therapeutic intervention currently used for the treatment of a variety of cancers and non-oncological disorders [1,2,3]. (ii) the S1 state undergoes efficient intersystem crossing that generates the first excited triplet state of the molecule, T1 ; (iii) T1 state can relax back to the ground state following two types of processes: type I and type II photoreactions In the former case, the PS in the T1 state abstracts an electron from a reducing molecule in its vicinity, giving rise to highly reactive species (i.e., O2 ́ , NO, ROO, RO) able to damage the targeted cells. In the latter one, supposed as the predominant process, the energy of the T1 state is transferred to the molecular oxygen (3 Σg ) to yield singlet oxygen 1 O2 (1 ∆g ), which represents the putative cytotoxic agent. Together with specific chemical properties, an efficient PDT photosensitizer should possess: (i) a maximum absorption in the so-called therapeutic window (600 ́800 nm), allowing the treatment of deeper tumors; (ii) a high intersystem spin-crossing

Methods

Results

Conclusion