Can Expanded Bacteriochlorins Act as Photosensitizers in Photodynamic Therapy? Good News from Density Functional Theory Computations
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
... re 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. Molecules 2016, 21, 288 2 of 12 probability; (iii) a singlet-triplet energy gap greater than 0.98 eV (the amount of energy required to activate the molecular oxygen) and, consequently, good singlet oxygen quantum yield (Φ ∆ ). In the last decades, several porphyrin-like systems and their metal complexes have been extensively studied at both theoretical          and experimental [13, 14] levels in view of their potential application in photodynamic therapy. These compounds present low dark toxicity, thermodynamic stability and interesting absorption properties in the Q region of the spectrum, which can be further modulated by varying the π delocalization. Moreover, they can easily form metal complexes and can be successfully functionalized with heavy atoms with a consequent increasing of the intersystem spin crossing efficiency  . Several porphyrin-like compounds and their complexes are already used in PDT and some of them are currently in advanced phases of clinical trials  . Among porphyrin-like systems, bacteriochlorins have emerged as a class of compounds that meet most of the requirements for ideal PDT agents                  . They are tetrapyrrole compounds with two opposing pyrroline rings, resulting from the reduction of the two pyrrole rings in the tetrapyrrole macrocycle of the correspondent porphyrins. The macrocycle structure occurs naturally in photosynthetic pigments (bacteriochlorophylls a and b) found in purple photosynthetic bacteria  . The bacteriochlorins are characterized by very high molar absorption coefficients in the therapeutic window (600-800 nm) and, accordingly, may be effective at lower concentrations. Therefore, the presence of pyrroline moiety has a noticeable effect on the absorption spectra, as neither chlorins nor porphyrins absorb in the NIR spectral region that ensures a deeper penetration of light in tissue compared to porphyrin derivatives. Recent advances in this field have shown how new synthetic bacteriochlorins attained the photostability, long-lived triplet states, and high quantum yields in the generation of ROS, all of these being essential properties for PDT photosensitizers  . Herein, the photophysical properties of a series of expanded bacteriochlorins (see Scheme 1) have been investigated with the aim to assess whether some of these recently synthesized compounds  could be proposed as photosensitizers in PDT. As largely documented several photophysical properties can be accurately predicted and rationalized from first principles calculations                   . Among these, the maximum absorption wavelengths, the singlet-triplet energy gaps and key information on the intersystem spin crossing efficiency are the most important ones for PDT application. The present study provides a screening of the expanded bacteriochlorins properties which can help to select the best candidate as PDT agent.