Paulo J. O. Ferreira

Abstract Cancer is a very challenging disease to treat, both in terms of treatment efficiency and side-effects. To overcome these problems, there have been extensive studies regarding the possibility of improving treatment by employing combination therapy, and by exploring therapeutic modalities with reduced side-effects (such as photodynamic therapy (PDT)). Herein, this work has two aims: (i) to develop self-activating photosensitizers for use in light-free photodynamic therapy, which would eliminate light-related restrictions that this therapy currently possesses; (ii) to assess their co-treatment potential when combined with reference chemotherapeutic agents (Tamoxifen and Metformin). We synthesized three new photosensitizers capable of self-activation and singlet oxygen production via a chemiluminescent reaction involving only a cancer marker and without requiring a light source. Cytotoxicity assays demonstrated the cytotoxic activity of all photosensitizers for prostate and breast tumor cell lines. Analysis of co-treatment effects revealed significant improvements for breast cancer, producing better results for all combinations than just for the individual photosensitizers and even Tamoxifen. By its turn, co-treatment for prostate cancer only presented better results for one combination than for just the isolated photosensitizers and Metformin. Nevertheless, it should be noted that the cytotoxicity of the isolated photosensitizers in prostate tumor cells was already very appreciable.

Abstract This paper reports the standard (p degrees = 0.1 MPa) molar enthalpies of formation, in the gaseous phase, at T = 298.15 K, of acridone and N-methylacridone as (50.0 +/- 5.0) kJ . mol(1) and (60.6 +/- 4.3) kJ . mol(1), respectively. These data were obtained from experimental thermodynamic parameters, namely the standard molar enthalpies of formation, in the crystalline phase, at T = 298.15 K, derived from the standard molar enthalpies of combustion measured by static-bomb combustion calorimetry, and the standard molar enthalpies of sublimation, at T = 298.15 K, determined by Calvet microcalorimetry or the Knudsen effusion techniques. Additionally, the gas-phase enthalpies of formation were estimated by G3(MP2)//B3LYP calculations, using several hypothetical gas-phase reactions, and were compared with the corresponding ones determined experimentally. The gas-phase keto-enol tautomerization chemical equilibrium of acridone M 9-acridinol was analysed using the Boltzmann's distribution, being confirmed that the equilibrium favours the formation of the keto form. The bond dissociation enthalpies (N-H) and (C-H) and the gas-phase acidities were also determined. The electrostatic potential surfaces and the frontier molecular orbitals were determined for both compounds, allowing us to infer about their reactivity properties. Other properties studied include the HOMO-LUMO energy gap and the ionization potential. (C) 2017 Elsevier Ltd.

Abstract Coelenterazine is a widespread bioluminescent substrate for a diverse set of marine species. Moreover, its imidazopyrazinone core is present in eight phyla of bioluminescent organisms. Given their very attractive intrinsic properties, these bioluminescent systems have been used in bioimaging, photodynamic therapy of cancer, as gene reporter and in sensing applications, among others. While it is known that bioluminescence results from the thermolysis of high-energy dioxetanones, the mechanism and dioxetanone species responsible for the singlet chemiexcitation of Coelenterazine are not fully understood. The theoretical characterization of the reactions of model Coelenterazine dioxetanones showed that efficient chemiexcitation is caused by a neutral dioxetanone with limited electron and charge transfer, by accessing a region of the PES where ground and excited states are nearly-degenerated. This finding was supported by calculation of equilibrium constants, which showed that only neutral dioxetanone is present in conditions associated with bioluminescence. Moreover, while cationic amino acids easily protonate amide dioxetanone, anionic ones cannot deprotonate the neutral species. These results indicate that, contrary to existent theories, efficient chemiexcitation can occur with significant electron and/or charge transfer. In fact, these processes can be prejudicial to chemiexcitation, as anionic dioxetanones showed a less efficient chemiexcitation despite the occurrence of significant electron and charge transfer.

Abstract In this study, a theoretical approach was used to study the UV absorption of the UVB filter, 4- methylbenzylidene camphor. The main objective of this work was to design new UVA filters based on this rather photo- stable compound, so that photo- degradation in this UV region can be avoided without the use of other molecules. This objective was achieved by the simultaneous addition of two appropriate substituents, which led to red- shifts of up to 0.69 eV while maintaining appreciable oscillator strength. Also, useful structure- energy relationships were derived, which allow for the development of more UVA filters based on 4- methylbenzylidene camphor.

Abstract Species with three-membered rings and the amide linkage are well studied. A quick perusal of the literature with SciFinder finds some 50 000 references to cyclopropanes and almost 300 000 references to amides. In the current paper, we discuss the structure and energetics of two understudied three-membered ring amides, 1,2-oxaziridine-3-one (5) (simultaneously describable as the simplest cyclic carbamate and simplest hydroxamate) and aziridine-2,3-dione (7) (simultaneously describable as the simplest imide and simplest alpha-ketoamide), with but 5 and nearly 10 references, respectively, for these two classes of compounds. Neither 1,2-oxaziridine-3-one (5) nor aziridine-2,3-dione (7), nor any derivative thereof, has been isolated. Calculational theory ameliorates the paucity of experimental information. The current study reports our computational findings for these and related species (e.g., enols and imidols) where we have used the G3(MP2)//B3LYP method.