Alan R. Cabrera

Synthesis of new phosphorescent imidoyl-indazol and phosphine mixed ligand Cu(I) complexes – structural characterization and photophysical properties

Four mononuclear Cu(I) complexes were prepared, described as [Cu(N,N)2]PF6 (1) and [Cu(N,N)(P,P)]PF6 (2–4), where N,N is N-(1-(2H-indazol-2-yl)ethylidene)-2,6-diisopropylaniline and P,P are phosphine derived ancillary ligands (bis[2-(diphenylphosphino)phenyl]ether (POP), bis(diphenylphosphino)ethane (dppe) or 2 PPh3). These new species were characterized by NMR, FT-IR, elemental analyses, cyclic voltammetry, UV-Vis – emission spectroscopy, transient absorption spectroscopy and DFT calculations. In addition, complexes 1 and 2 were characterized by X-ray diffraction. The four complexes showed an MLCT absorption band between 400 and 450 nm, in addition to a weakly structured phosphorescence in a 4:1 ethanol:methanol glassy matrix at 77 K. Complexes 2–4 have emission profiles that resemble the phosphorescence of the protonated N,N ligand, suggesting a triplet LC character of the lowest lying excited state at 77 K. By contrast, a mixed MLCT/LC triplet emission is most likely responsible for the phosphorescence in complex 1. Weak ligand-centered emission is also detected in the solid state at room temperature but only in the case of complexes 2 and 4, suggesting thermally activated deactivation processes in the case of 1 and 3. Notably, the transient absorption spectroscopy of complexes 2–4 in CH2Cl2 solution confirms a strong contribution from a ligand-centered (LC) triplet excited state, pointing towards a mixed 3MLCT/3LC character of the transient species in solution at room temperature, undergoing a non-radiative deactivation in the μs time-scale. This behavior markedly differs from that observed for complex 1, whose short-lived 3MLCT excited state is followed by ultrafast transient absorption spectroscopy.

New imidoyl-indazole platinum (II) complexes as potential anticancer agents: Synthesis, evaluation of cytotoxicity, cell death and experimental-theoretical DNA interaction studies

Four new neutral N,N imidoyl-indazole ligands (L1, L3, L6, L7) and six new Pt(II)-based complexes (C1-5 and C7) were synthesized and characterized by spectroscopic and spectrometric techniques. Additionally, compounds L6, L7, C3, C5 and C7 were analyzed using X-ray diffraction. An evaluation of cytotoxicity and cell death in vitro for both ligands and complexes was performed by colorimetric assay and flow cytometry, in four cancer cell lines and VERO cells as the control, respectively. Cytotoxicity and selectivity demonstrated by each compound were dependent on the cancer cell line assayed. IC50 values of complexes C1-5 and C7 were lower than those exhibited for the reference drug cisplatin, and selectivity of these complexes was in general terms greater than cisplatin on three cancer cell lines studied. In HL60 cells, complexes C1 and C5 exhibited the lowest values of IC50 and were almost five times more selective than cisplatin. Flow cytometry results suggest that each complex predominantly induced necrosis, and its variant necroptosis, instead of apoptosis in all cancer cell lines studied. DNA binding assays, using agarose gel electrophoresis and UV-visible spectrophotometry studies, displayed a strong interaction only between C4 and DNA. In fact, theoretical calculations showed that C4-DNA binding complex was the most thermodynamic favorable interaction among the complexes in study. Overall, induction of cell death by dependent and independent-DNA-metal compound interactions were possible using imidoyl-indazole Pt(II) complexes as anticancer agents.

Substituent influence in phenanthroline-derived ancillary ligands on the excited state nature of novel cationic Ir(III) complexes

In the quest for coordination compounds with potential applications in energy conversion processes, a new series of four Ir(III) complexes (C1–4) of the type [Ir(R-ppy)2(Ln)](PF6), where R-ppy = 2-phenylpyridine (ppy) or 2,4-difluorophenylpyridine (F2-ppy) and Ln = 1-methyl-1H-pyrazole[3′,4′:5,6]pyrazino[2,3-f][1,10]phenanthroline (L1) or thieno[3′,4′:5,6]pyrazino[2,3-f][1,10]phenanthroline (L2) has been synthesized. The photophysical properties of these compounds have been thoroughly characterized by both steady-state and time-resolved spectroscopic techniques, pointing out a complex interplay between excited states of different nature that plays a crucial role in the deactivation processes. In the case of complexes C1–2 that feature the same L1 ancillary ligand, the lowest excited states at room temperature are characterized by an admixture between the 3MLCT/3LLCT and 3LC states, with an almost pure 3LC character in C2. For C3–4, the admixture among charge-transfer and ligand-centred states is negligible, due to the appreciably low energy of the LC one, which, however, plays a non-innocent role in the deactivation pathway of the triplet charge-transfer emissive states of complexes C3–4. This work thus highlights the importance of a detailed comprehension of the photophysical properties of Ir(III) complexes in view of their use in energy transformation systems.

Heteroleptic Cu(I) complexes bearing methoxycarbonyl-imidoylindazole and POP ligands – an experimental and theoretical study of their photophysical properties

Four new mixed ligand Cu(I) complexes bearing methoxycarbonyl imidoyl-indazole and bis[2-(diphenylphosphino)-phenyl]ether (POP) ligands were synthesized and characterized by variable-temperature NMR, FT-IR, EA and HRMS. For three of them, the molecular structures were obtained by X-ray diffraction analysis. The electrochemical and absorption–emission properties of all the complexes were investigated by using cyclic voltammetry, UV-Vis spectroscopy, and spectrofluorometric measurements in a CH2Cl2 solution at room temperature and in different solid-state matrices. In addition, quantum chemical computations were performed to gain insight into their electronic and photophysical properties. The complexes showed an MLCT band, which is more influenced by the position of the electron-withdrawing methoxycarbonyl substituent in the indazole ring rather than by the π-extension introduced by the alkene moiety. Besides, all the complexes were found to be weak emitters in the CH2Cl2 solution while they were brighter emitters in the solid-state.

(-)-Shikimic Acid as a Chiral Building Block for the Synthesis of New Cytotoxic 6-Aza-Analogues of Angucyclinones

We describe the syntheses of nine new angucyclinone 6-aza-analogues, achieved through a hetero Diels-Alder reaction between the shikimic acid derivative-azadiene 13, with different naphthoquinones. The cytotoxic activity of the new synthesized compounds and five angucyclinones, previously reported, was evaluated in vitro against three cancer cell lines: PC-3 (prostate cancer), HT-29 (colon cancer), MCF-7 (breast cancer), and one non-tumoral cell line, human colon epithelial cells (CCD841 CoN). Our results showed that most 6-azadiene derivatives exhibited significant cytotoxic activities, which was demonstrated by their IC50 values (less than 10 μM), especially for the most sensitive cells, PC-3 and HT-29. From a chemical point of view, depending on the protected group of ring A and the pattern of substitution on ring D, cytotoxicity elicited these compounds, in terms of their potency and selectivity. Therefore, according to these chemical features, the most promising agents for every cancer cell line were 7a, 17, and 19c for PC-3 cells; 7a, 17, and 20 for HT-29 cells, and 19a for MCF-7 cells.