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Biosubstrate-sensitizer binding is one of the factors that enhances the type-I mechanism over the type-II in the whole photodynamic process. 2,7,12,17-Tetraphenylporphycene (TPPo), a second-generation photosensitizer, is a hydrophobic compound with good photophysical properties for photodynamic therapy applications that has proved its ability for the photoinactivation of different cell lines. Nevertheless, little is known about its mechanism of action. This paper focuses on the study of the interaction/binding of TPPo with different model biomolecules that may favor the type-I mechanism in the overall photodynamic process, including nucleosides, proteins, and phospholipids. Compared with more hydrophilic photosensitizers, it is concluded that TPPo is more likely to undergo type-II (singlet oxygen) than type-I (electron transfer) photodynamic processes in biological environments.

The effects of 9-substitution on the photophysical properties of tetraphenylporphycenes (TPPo) have been examined using an electron acceptor, an electron donor, and an electroneutral substituent as model compounds. Introduction of the acetoxy group enhances the fluorescence ability of the compound, with only a small reduction in the singlet oxygen quantum yield. The optical and photophysical properties of a nitro-porphycene are reported for the first time. The compound is emerald green, contrasting with the typical blue color of porphycenes. While this compound is much less fluorescent than unsubstituted TPPo, its singlet oxygen quantum yield is only slightly lower, almost identical to that of the 9-acetoxy compound (9-AcOTPPo). Finally, the electron-donor amino group is found to induce the greatest changes in the porphycene photophysics, decreasing strongly its fluorescence and singlet oxygen quantum yields. With the exception of such electron donors, introduction of substituents at the 9 (meso) position of tetraphenylporphycenes is not detrimental to their photophysics and photosensitizing ability and thus can be exploited for targeted photodynamic therapy purposes.

Photodynamic therapy (PDT) is a rapidly expanding alternative to the treatment of solid tumors and other highly-proliferative diseases due to its many attractive features: high selectivity, repeatability, and lack of serious adverse effects. The five drugs approved for use in PDT to date suffer from different problems that limit their efficacy and safety. Current understanding of cell death mechanisms offers an opportunity for the development of new, more efficient and safer drugs. This highlight describes the efforts of our research group in the PDT field: chemical development of porphycenes as PDT photosensitizers, photophysical screening of new families of potential PDT agents, and development of spectroscopic techniques for directly monitoring singlet oxygen and thus better understand the production, diffusion, and reactivity of this primary cytotoxic species in cells.

The nitration reaction of 2,7,12,17-tetraphenylporphycene has been studied. The use of AgNO₃ and a mixture of acetic acid and 1,2-dichloroethane as a mild nitrating system provides an optimized preparation of 9-nitro-2,7,12,17-tetraphenylporphycene and a regioselective synthesis of 9,20-dinitro-2,7,12,17-tetraphenylporphycene. While 25 min of reaction are needed to obtain the mononitrated compound, 4 h are necessary to yield a mixture of 9,20-dinitro and 9,19-dinitro 2,7,12,17- tetraphenylporphycene in a proportion of 3 to 1. From this mixture, the geometric isomers can be isolated by fractional crystallization. 9-Nitro-2,7,12,17-tetraphenylporphycene can be reduced to the corresponding amino derivative, which is the starting material to obtain 9-(glutaric methylesteramide)- 2,7,12,17-tetraphenylporphycene, a versatile derivative useful for conjugation.

A series of benzoporphycenes and naphthoporphycenes and their zinc complexes were prepared from bicyclo[2.2.2]octadiene fused porphycenes by a retro-Diels-Alder reaction and their photophysical properties were studied. Free-base tetranaphthoporphycene was not soluble in common organic solvents, but zinc tetranaphthoporphycene was slightly soluble in pyridine and showed B- and Q-bands at 507 and 690 nm, respectively. Dinaphthoporphycene showed broad B- and Q-bands due to its lower symmetry. Tetrabenzo-, dibenzo-, and dinaphthoporphycenes showed fluorescence at 673, 654, and 670 nm with quantum yields of 0.32, 0.42, and 0.31, respectively, although their precursors were non-fluorescent. Zinc complexes of tetrabenzo-, dibenzo-, tetranaphtho-, dinaphthoporphycenes and their bicyclo[2.2.2]octadiene-fused precursors revealed moderate fluorescence with quantum yields of 0.15–0.37. The crystal structures of tetrabenzo- and dibenzoporphycenes showed herringbone structures, while the zinc tetrabenzoporphycene showed a hexagonal box-structure with six pyridine ligands inside.

The synthesis and characterization of four metalloporphycenes containing a [MCp*]⁺ (Cp* = pentamethylcyclopentadiene; M = Rh, Ir, and Ru) fragment directly bonded to the π-framework of the macrocycle were obtained. The electrochemical and optical properties of these complexes, studied in their respective free-base forms, revealed that the electron acceptor properties of the macrocycle can be enhanced by the coordination of an organometallic fragment to the π-electron face. In the case of the "fused" ruthenocene adduct, the corresponding nickel complex was also prepared. Here, less electronic communication between the ruthenocene moiety and the macrocycle was seen; however, the basic electron acceptor properties of the macrocycle were retained.

The photophysical properties of toluene solutions of two new 22π expanded porphycene compounds were measured using a combination of various steady-state and time-resolved techniques. The determined triplet energy (E_T= 109 ± 3) kJ.mol^-1, coincident with the calculated E_T = (96.0 ± 10) kJ.mol^-1, of both red absorbing compounds is higher than the energy required to excite ground state molecular oxygen to singlet molecular oxygen. However, the intersystem crossing yield is very low (ca. 10^-2), which makes these compounds poor photosensitizers. The triplet state yield of the two expanded 22π porphyrinoid compounds is much lower than that of the parent porphycene, whereas their fluorescence is as high (ca. 30%) as the value for porphycene. The slower than diffusional quenching rate constant of a porphycene triplet state by the two new compounds reflects a steric hindering factor of the exothermic energy transfer.

Nitration of 2,7,12,17-tert-butylporphycene, leading mainly to meso-substituted 9-nitro- and 9,20-nitro- derivatives, also yielded a small amount of porphycene bearing three tert-butyl moieties and the nitro group at the $\beta$ position. The electronic absorption spectra of 2-nitro and 9-nitroporphycenes are similar, but the photophysical characteristics strongly differ. Unlike the meso-substituted derivative, 2-nitroporphycene emits intense, long-lived (ns) fluorescence. Strong enhancement of fluorescence intensity is due to the absence of steric interactions between tert-butyl and nitro moieties. The two porphycenes also differ in their tautomeric properties. 2-nitroporphycene exists in one trans-tautomeric form, whereas two trans-tautomers of similar energies coexist in the meso derivative. These results are well reproduced by quantum-chemical calculations. The possibility of changing photophysics and tautomerism by shifting the position of the substituent may be exploited while designing porphycenes targeted for specific applications, such as photodynamic therapy or building molecular switches.

9-aminoporphycenes degrade over time, yielding products that emit in a similar spectral region as the parent compounds. This leads to a triple fluorescence pattern, with relative intensities changing with time, solvent, excitation wavelength, and irradiation. The decomposition products were analyzed using chromatography coupled with mass spectrometry, absorption, and emission measurements. The spectra of possible products were also calculated using density functional theory. We conclude that the degradation processes involve oxygenation that occurs both in the ground electronic state and as a photoinduced process, the latter being more efficient.