PAPER www.rsc.org/pps | Photochemical & Photobiological Sciences Can subpyriporphyrin and its boron complex be proposed as photosensitizers in photodynamic therapy? A first principle time dependent study Ida Lanzo, Angelo D. Quartarolo, Nino Russo and Emilia Sicilia Received 8th October 2008, Accepted 5th January 2009 First published as an Advance Article on the web 16th January 2009 DOI: 10.1039/b817718j Density functional theory (DFT) and its time-dependent approach (TDDFT) in conjunction with the PBE0 exchange–correlation functional have been employed to characterize the structural and electronic properties of a new synthesized homologue of a triphyrin, in which a pyrrole ring has been substituted with a pyridine moiety, and its boron complex. Absorption spectra have been computed for different isomers of the free compound as well as for the corresponding boron containing system. The solvent effects have been evaluated through the polarizable continuum model (PCM). Triplet energies have been computed in order to verify whether these systems should be proposed as photosensitizers in photodynamic therapy. Results show that the employed tool is able to correctly reproduce the absorption spectra and to contribute to better assign the electronic transitions explaining their origin and that the examined boron complex has a triplet energy that, in principle, can activate the singlet O 2 reactive species. 1. Introduction The porphyrins and their expanded ring analogues are the most studied macrocyclic ring systems since their peculiar electronic structures give rise to numerous properties that make these systems particularly interesting in a wide range of applications going from nonlinear optics, to photonic devices, to dye technologies. 1–3 Less effort has been devoted to synthesize and characterize contracted porphyrinoids such as subphtalocyanines, 4,5 subporphyrazines 6,7 tribenzosubporphyrins 8,9 and subporphyrins 10,11 that contain three pyrrole or isoindole moieties. Contrary to porphyrins and their expanded ring analogues, these systems comprise a 14-p-electron aromatic core, often adopt a nonplanar conformation and con- sequently reveal very interesting spectral and electronic features 4 potentially useful for their application in many fields of modern technologies. The absorbance spectra in the UV/Vis region of the subporphyrinoids are blue-shifted with respect to the more expanded porphyrin-like systems due to their small p-conjugated cores and are intensively coloured from orange to deep red. These characteristics make them potential candidates in high-density optical data storage technology. 4 Recently, subpyriporphyrin, hereafter denoted SPP (see Scheme 1), which is a novel type of contracted porphyrin, a homologue of [14]thriphyrin(1.1.1) in which one pyrrole ring has been substituted with a pyridine moiety, has been synthesized as a free ligand and as a boron containing complex. 10 The absorption spectra of these new compounds are interesting and contain transitions in both B and Q bands. The reported UV/Vis absorption spectra 10 are not well assigned and the origin of the electronic transitions are not known. Since the considered systems show transition energies in the Q band (greater than 500 nm), in principle they should be active in photodynamic therapy (PDT). This non-invasive therapy is Dipartimento di Chimica and Centro di Calcolo ad Alte Prestazioni per Elaborazioni Parallele e Distribuite-Centro d’Eccellenza MURST, Universita’ della Calabria, I-87030, Arcavacata di Rende, (CS), Italy currently used for the treatment of a variety of diseases in oncology, but is explored also in the areas of cardiology, ophthalmology, der- matology, immunology, gynaecology, urology 12–15 and microbial infections. 16 In PDT a non-toxic photosensitizer is introduced in the body of the appropriate target and is irradiated with a wavelength light ranging from 600 to 900 nm (the so-called therapeutic window), in order to excite the photosensitizer from its ground state (S 0 ) in a short-lived first excited state (S 1 ). Furthermore, S 1 can undergo conversion to the first excited triplet state (T 1 ) by intersystem crossing. Then the T 1 state of the sensitizer can release its energy to the surrounding biological tissue, exciting the O 2 from its triplet ( 3 R g ) to the highly reactive singlet state ( 1 D g ) that induces an oxidative cellular damage leading to the apoptosis or necrosis of the cells. In order to contribute to give further insights into the origin of these transitions, to better characterize the optical spectra of these new synthesized macrocycles and to verify whether their electronic properties are interesting for their possible use in PDT, we have undertaken a systematic study of the structure and electronic properties of different isomers of the free species as well as of their boron complexes (see Scheme 1). 2. Computational method The study has been performed at density functional (DF) level of theory and employing its time dependent extension (TD- DFT). 17 Full geometry optimization for each studied free lig- and and corresponding boron complex has been carried out using the Turbomole program 18 employing the PBE0 19 exchange– correlation functional and the SVP and TZVP all electron basis sets. 20 The PBE0 functional, based on the generalized gradient functional PBE 20 with 25% exact exchange, has been chosen as it generally reproduces geometrical parameters, including in metal containing systems, within experimental error. 19 As recently 386 | Photochem. Photobiol. Sci., 2009, 8, 386–390 This journal is © The Royal Society of Chemistry and Owner Societies 2009