Ruthenium complexes of two different non-innocent ligands. Investigation of electronic structural aspects by experimental and DFT analysis

Synthesis and characterisation of the ruthenium complexes, [RuII(Q)(tppz)(Cl)]ClO4 (1) and [{RuII(Q)Cl}2- (µ-tppz)](ClO4)2 (2), incorporating redox noninnocent ligands, (Q = o-benzoquinonediimine, tppz = 2,3,5,6-tetrakis- (2-pyridyl)pyrazine) are reported. The crystal structure of (1) and DFT optimized structure of (2) in comparison with the reported structures of analogous molecules establish that their valence configurations comprise the fully oxidized Q° and tppzo along with the Ru(II) center as well as non-planarity of the coordinated tppz. The reversible RuII/RuIII oxidation of (1) and two successive RuII/RuIII couples for (2) appear at 0.95 V and 0.96, 1.11 V vs SCE in CH3CN, respectively. The separation in potential of 0.15 V between the two successive oxidation processes in (2) leads to the comproportionation constant, Kc value of 3.5× 102, which implies a rather weakly coupled (electrochemical) valence localized class II mixed valent RuIIRuIII state in (2)+. However, the DFT calculated Mulliken spin densities of (2)+ (Ru1, Ru2, Q, tppz and Cl of 0.333, 0.412, 0.070, -0.006 and 0.221, respectively) suggest an almost valence averaged situation. The compositions of molecular orbitals of (1) and (2) suggest appreciable (d)RuII-> π (tppz)/π (Q) back-bonding. Both the complexes exhibit multiple close-by reductions within the potential range of 0 to -2.0 V vs SCE in CH3CN which are assigned to be the ligand (Q/tppz) based reductions. The molecular orbital compositions predict Q based first reduction followed by tppz-based successive reductions in (1), whereas in (2) first reduction primarily takes place at the bridging tppz center followed by the reduction of Q. (1) and (2) exhibit multiple metal-to-ligand charge transfer transitions in the visible region due to the presence of two and three acceptor ligands, respectively. The key transitions in the visible region are assigned based on the TD-DFT calculations on optimized structures of (1) and (2)

Ruthenium complexes of two different non-innocent ligands. Investigation of electronic structural aspects by experimental and DFT analysis

1324-1333Synthesis and characterisation of the ruthenium complexes, [RuII(Q)(tppz)(Cl)]ClO4 (1) and [{RuII(Q)Cl}2- (m-tppz)](ClO4)2 (2), incorporating redox noninnocent ligands, (Q = o-benzoquinonediimine, tppz = 2,3,5,6-tetrakis- (2-pyridyl)pyrazine) are reported. The crystal structure of (1) and DFT optimized structure of (2) in comparison with the reported structures of analogous molecules establish that their valence configurations comprise the fully oxidized Qo and tppzo along with the Ru(II) center as well as non-planarity of the coordinated tppz. The reversible RuII/RuIII oxidation of (1) and two successive RuII/RuIII couples for (2) appear at 0.95 V and 0.96, 1.11 V vs SCE in CH3CN, respectively. The separation in potential of 0.15 V between the two successive oxidation processes in (2) leads to the comproportionation constant, Kc value of 3.5X102, which implies a rather weakly coupled (electrochemical) valence localized class II mixed valent RuIIRuIII state in (2)+. However, the DFT calculated Mulliken spin densities of (2)+ (Ru1, Ru2, Q, tppz and Cl of 0.333, 0.412, 0.070, -0.006 and 0.221, respectively) suggest an almost valence averaged situation. The compositions of molecular orbitals of (1) and (2) suggest appreciable (d)RuII->*(tppz)/*(Q) back-bonding. Both the complexes exhibit multiple close-by reductions within the potential range of 0 to -2.0 V vs SCE in CH3CN which are assigned to be the ligand (Q/tppz) based reductions. The molecular orbital compositions predict Q based first reduction followed by tppz-based successive reductions in (1), whereas in (2) first reduction primarily takes place at the bridging tppz center followed by the reduction of Q. (1) and (2) exhibit multiple metal-to-ligand charge transfer transitions in the visible region due to the presence of two and three acceptor ligands, respectively. The key transitions in the visible region are assigned based on the TD-DFT calculations on optimized structures of (1) and (2)

ΔPSap4#5 surface-functionalized abiraterone-loaded nanoparticle successfully inhibits carcinogen-induced prostate cancer in mice: a mechanistic investigation

Abstract Prostate cancer (PCa) is one of the fatal illnesses among males globally. PCa-treatment does not include radiotherapy. Chemotherapy eventually causes drug resistance, disease recurrence, metastatic advancement, multi-organ failure, and death. Preclinical data on PCa-induced by carcinogens are truly scarce. Although some data on xenograft-PCa in animals are available, they mostly belonged to immuno-compromised animals. Here, we developed ΔPSap4#5 aptamer surface-functionalized abiraterone-loaded biodegradable nanoparticle (Apt-ABR-NP) to investigate its targeting ability to prostate-specific membrane antigen (PSMA) in carcinogen-induced PCa mice and the therapeutic efficacy of the formulation. Aptamers are called synthetic monoclonal antibodies for their target specificity. However, they are devoid of the toxicity problem generally associated with the antibody. Abiraterone is a testosterone and androgen inhibitor, a new drug molecule that shows good therapeutic efficacy in PCa. The developed nanoparticles were physicochemically characterized and used for various in vitro and in vivo investigations. Nanoparticles had an average size of 149 nm with sustained drug release that followed Korsmeyer–Peppas kinetics. In vitro investigation showed that Apt-ABR-NP produced 87.4% apoptotic cells and 95.3% loss of mitochondrial membrane potential in LNCaP cells after 48 h of incubation. In vivo gamma scintigraphy, live imaging, and biodistribution studies in prostate cancer animal models showed the predominant targeting potential of Apt-ABR-NP. Histopathological investigation showed the remarkable therapeutic efficacy of the formulation. The pharmacokinetic study showed an increased biological half-life and enhanced blood residence time of Apt-ABR-NP. Apt-ABR-NP therapy can thus minimize off-target cytotoxicity, reduce drug loss due to site-specific delivery, and deliver abiraterone in a sustained manner to the organ of interest. Thus, the present study brings new hope for better therapeutic management of PCa in the near future. Graphical Abstrac