Green Light-Triggered Photocatalytic Anticancer Activity of Terpyridine-Based Ru(II) Photocatalysts.

The relentless increase in drug resistance of platinum-based chemotherapeutics has opened the scope for other new cancer therapies with novel mechanisms of action (MoA). Recently, photocatalytic cancer therapy, an intrusive catalytic treatment, is receiving significant interest due to its multitargeting cell death mechanism with high selectivity. Here, we report the synthesis and characterization of three photoresponsive Ru(II) complexes, viz., [Ru(ph-tpy)(bpy)Cl]PF6 (Ru1), [Ru(ph-tpy)(phen)Cl]PF6 (Ru2), and [Ru(ph-tpy)(aip)Cl]PF6 (Ru3), where, ph-tpy = 4'-phenyl-2,2':6',2″-terpyridine, bpy = 2,2'-bipyridine, phen = 1,10-phenanthroline, and aip = 2-(anthracen-9-yl)-1H-imidazo[4,5-f][1,10] phenanthroline, showing photocatalytic anticancer activity. The X-ray crystal structures of Ru1 and Ru2 revealed a distorted octahedral geometry with a RuN5Cl core. The complexes showed an intense absorption band in the 440-600 nm range corresponding to the metal-to-ligand charge transfer (MLCT) that was further used to achieve the green light-induced photocatalytic anticancer effect. The mitochondria-targeting photostable complex Ru3 induced phototoxicity with IC50 and PI values of ca. 0.7 µM and 88, respectively, under white light irradiation and ca. 1.9 µM and 35 under green light irradiation against HeLa cells. The complexes (Ru1-Ru3) showed negligible dark cytotoxicity toward normal splenocytes (IC50s > 50 µM). The cell death mechanistic study revealed that Ru3 induced ROS-mediated apoptosis in HeLa cells via mitochondrial depolarization under white or green light exposure. Interestingly, Ru3 also acted as a highly potent catalyst for NADH photo-oxidation under green light. This NADH photo-oxidation process also contributed to the photocytotoxicity of the complexes. Overall, Ru3 presented multitargeting synergistic type I and type II photochemotherapeutic effects.

Comparative Study of Sonodynamic and Photoactivated Cancer Therapies with Re(I)-Tricarbonyl Complexes Comprising Phenanthroline Ligands.

Herein, we have compared the effectivity of light-based photoactivated cancer therapy and ultrasound-based sonodynamic therapy with Re(I)-tricarbonyl complexes (Re1-Re3) against cancer cells. The observed photophysical and TD-DFT calculations indicated the potential of Re1-Re3 to act as good anticancer agents under visible light/ultrasound exposure. Re1 did not display any dark- or light- or ultrasound-triggered anticancer activity. However, Re2 and Re3 displayed concentration-dependent anticancer activity upon light and ultrasound exposure. Interestingly, Re3 produced 1O2 and OH• on light/ultrasound exposure. Moreover, Re3 induced NADH photo-oxidation in PBS and produced H2O2. To the best of our knowledge, NADH photo-oxidation has been achieved here with the Re(I) complex for the first time in PBS. Additionally, Re3 released CO upon light/ultrasound exposure. The cell death mechanism revealed that Re3 produced an apoptotic cell death response in HeLa cells via ROS generation. Interestingly, Re3 showed slightly better anticancer activity under light exposure compared to ultrasound exposure.

Towards Selective Delivery of a Ruthenium(II) Polypyridyl Complex-Containing Bombesin Conjugate into Cancer Cells.

An increasing number of novel Ru(II) polypyridyl complexes have been successfully applied as photosensitizers (PSs) for photodynamic therapy (PDT). Despite recent advances in optimized PSs with refined photophysical properties, the lack of tumoral selectivity is often a major hurdle for their clinical development. Here, classical maleimide and versatile NHS-activated acrylamide strategies were employed to site-selectively conjugate a promising Ru(II) polypyridyl complex to the N-terminally Cys-modified Bombesin (BBN) targeting unit. Surprisingly, the decreased cell uptake of these novel Ru-BBN conjugates in cancer cells did not hamper the high phototoxic activity of the Ru-containing bioconjugates and even decreased the toxicity of the constructs in the absence of light irradiation. Overall, although deceiving in terms of selectivity, our new bioconjugates could still be useful for advanced cancer treatment due to their nontoxicity in the dark.

Formation of the N≡N Triple Bond from Reductive Coupling of a Paramagnetic Diruthenium Nitrido Compound.

Construction of nitrogen-nitrogen triple bonds via homocoupling of metal nitrides is an important fundamental reaction relevant to a potential Nitrogen Economy. Here, we report that room temperature photolysis of Ru2(chp)4N3 (chp- = 2-chloro-6-hydroxypyridinate) in CH2Cl2 produces N2 via reductive coupling of Ru2(chp)4N nitrido species. Computational analysis reveals that the nitride coupling transition state (TS) features an out-of-plane "zigzag" geometry instead of the anticipated planar zigzag TS. However, with intentional exclusion of dispersion correction, the planar zigzag TS geometry can also be found. Both the out-of-plane and planar zigzag TS geometries feature two important types of orbital interactions: (1) donor-acceptor interactions involving intermolecular donation of a nitride lone pair into an empty Ru-N π* orbital and (2) Ru-N π to Ru-N π* interactions derived from coupling of nitridyl radicals. The relative importance of these two interactions is quantified both at and after the TS. Our analysis shows that both interactions are important for the formation of the N-N σ bond, while radical coupling interactions dominate the formation of N-N π bonds. Comparison is made to isoelectronic Ru2-oxo compounds. Formation of an O-O bond via bimolecular oxo coupling is not observed experimentally and is calculated to have a much higher TS energy. The major difference between the nitrido and oxo systems stems from an extremely large driving force, ∼-500 kJ/mol, for N-N coupling vs a more modest driving force for O-O coupling, -40 to -140 kJ/mol.

Lysosome-targeted ruthenium(II) complexes induce both apoptosis and autophagy in HeLa cells.

Ruthenium complexes with good biological properties have attracted increasing attention in recent decades. In this work, three ruthenium polypyridine complexes containing 5-fluorouracil derivatives as ligands, [Ru(bpy)2(L)]2+ (Ru1), [Ru(phen)2(L)]2+ (Ru2), [Ru(dip)2(L)]2+ (Ru3) (L = 1-((1,10-phenanthroline-5-amino) pentyl)-5-fluorouracil; bpy = 2,2'-bipyridine; phen =1,10-phenanthroline; dip = 4,7-diphenyl-1,10-phenanthroline), were synthesized and characterized. Based on in vitro cytotoxicity tests, Ru3 (IC50 = 7.35 ± 0.39 µM) showed the best anticancer activity among three compounds in the selected cell lines. It is worth noting that Ru3 also exerts less cytotoxicity on LO2 cell lines, with an IC50 value 5 times higher than that on HeLa cells, indicating its selective activity. Mechanism studies revealed that Ru3 can specifically target lysosomes and induce cell apoptosis in a caspase-dependent manner. Specifically, Ru3 can arrest cell cycle at the G0/G1 phase, increase the intracellular reactive oxygen species (ROS) level, and then damage DNA. In short, Ru3 can eventually cause cell death through the synergy of inducing apoptosis and autophagy, which was further proven by western blot assay results.

Single-Cell Chemistry of Photoactivatable Platinum Anticancer Complexes.

The Pt(IV) prodrug trans, trans, trans-[Pt(pyridine)2(N3)2(OH)2] (Pt1) and its coumarin derivative trans, trans, trans-[Pt(pyridine)2(N3)2(OH)(coumarin-3-carboxylate)] (Pt2) are promising agents for photoactivated chemotherapy. These complexes are inert in the dark but release Pt(II) species and radicals upon visible light irradiation, resulting in photocytotoxicity toward cancer cells. Here, we have used synchrotron techniques to investigate the in-cell behavior of these prodrugs and visualize, for the first time, changes in cellular morphology and Pt localization upon treatment with and without light irradiation. We show that photoactivation of Pt2 induces remarkable cellular damage with extreme alterations to multiple cellular components, including formation of vacuoles, while also significantly increasing the cellular accumulation of Pt species compared to dark conditions. X-ray absorption near-edge structure (XANES) measurements in cells treated with Pt2 indicate only partial reduction of the prodrug upon irradiation, highlighting that phototoxicity in cancer cells may involve not only Pt(II) photoproducts but also photoexcited Pt(IV) species.

An Activatable Near-Infrared Fluorescence Probe for in Vivo Imaging of Acute Kidney Injury by Targeting Phosphatidylserine and Caspase-3.

Renal-clearable and target-responsive near-infrared (NIR) fluorescent imaging probes have been promising for in vivo diagnosis of acute kidney injury (AKI). However, designing an imaging probe that is renal-clearable and concurrently responsive toward multiple molecular targets to facilitate early detection of AKI with improved sensitivity and specificity is challenging. Herein, by leveraging the receptor-mediated binding and retention effect along with enzyme-triggered fluorescence activation, we design and synthesize an activatable small-molecule NIR fluorescent probe (1-DPA2) using a "one-pot sequential click reaction" approach. 1-DPA2 can target both the externalized phosphatidylserine (PS) and active caspase-3 (Casp-3), two essential biomarkers of apoptosis, producing enhanced 808 nm NIR fluorescence and a high signal-to-background ratio (SBR) amenable to detecting the onset of cisplatin-induced AKI in mice as early as 24 h post-treatment with cisplatin. We not only monitor the gradual activation of Casp-3 in the kidney of mice upon AKI progression but also can report on the progressive recovery of kidney functions in AKI mice following N-acetyl-l-cysteine (NAC) therapy via real-time fluorescence imaging by 1-DPA2. This study demonstrates the ability of 1-DPA2 for longitudinal monitoring of renal cell apoptosis by concurrently targeting PS externalization and Casp-3 activation, which is efficient for early diagnosis of AKI and useful for prediction of potential drug nephrotoxicity as well as in vivo screening of anti-AKI drugs' efficacy.

Ultrasmall Zwitterionic Polypeptide-Coordinated Nanohybrids for Highly Efficient Cancer Photothermal Ferrotherapy.

Ferroptosis therapy (FT) based on the Fenton reaction of ferrous nanoparticles has been becoming a unique strategy for cancer treatment; however, current ferrous nanoparticles suffer from slower Fenton reaction kinetics, lower ferroptosis efficacy, and long-term toxicity, so it is urgent to construct biocompatible ferrous nanomaterials with highly efficient Fenton reaction activity for cancer FT. Inspired by single-atom catalysis and size-determined tumor penetration, we conceived an innovative strategy for constructing ultrasmall zwitterionic polypeptide-coordinated nanohybrids of PCGA@FeNP with about 6 nm by utilizing thiol/hydroxyl-iron cooperative coordination chemistry. The ultrasmall size, unsaturated ferrous coordination, and intracellular acidic pH could accelerate the Fenton reaction, thus boosting the efficacy of ferroptosis. Moreover, those coordinated nanohybrids exhibited prominent photothermia with 59.5% conversion efficiency, further accelerating the Fenton reaction and inducing a synergistic effect between FT and photothermal therapy (PTT). In vitro and in vivo GPX-4 expression ascertained that PCGA@FeNP indeed induced effective FT and synergistic FT-PTT. Remarkably, in vivo FT-PTT completely ablated 4T1 solid tumors by one treatment, presenting outstanding and synergistic antitumor efficacy via the photothermia-boosted ferroptosis and apoptosis pathways. This work supplies a practicable strategy to fabricate ultrasmall zwitterionic coordination nanohybrids for highly efficient cancer FT and FT-PTT theranostics with potential clinical transitions.

Conjugated Coordination Porphyrin-based Nanozymes for Photo-/Sono-Augmented Biocatalytic and Homologous Tumor Treatments.

Porphyrin-based nanozymes (Porzymes) have shown promising application potential to fight against tumors using catalytically generated reactive oxygen species from the excessively produced H2O2 in the tumor microenvironment. However, the low coordination porphyrin (CP) loading ratio, difficult controllable nanostructure, low bioavailability, and low biocatalytic activities of current established Porzymes have severely limited their antitumor applications. Here, a novel malignant melanoma cell membrane-coated Pd-based CP nanoplatform (Trojan Porzymes) has been synthesized for biocatalytic and homologous tumor therapies. The Trojan Porzymes exhibit a high CP loading ratio, uniform nanoscale size, single-atom nanostructure, homologous targeted ability, and high-efficiency photo/sono-augmented biocatalytic activities. The enzyme-like biocatalytic experiments display that the Trojan Porzymes can generate abundant •OH via chemodynamic path and 1O2 via visible light or ultrasound excitation. Then we demonstrate that the Trojan Porzymes show homologous targeting ability to tumor cells and can achieve efficient accumulation and long-term retention in cancer tissues. Our in vivo data further disclose that the photo/sono-assisted chemodynamic therapies can significantly augment the treatment efficiency of malignant melanoma. We believe that our work will afford a new biocatalytic and homologous strategy for future clinical malignant melanoma treatments, which may inspire and guide more future studies to develop individualized biomedicine in precise tumor therapies.

Energy transfer processes and structure of carboxymethyl cellulose-Tb/Eu nanocomplexes with color-tunable photoluminescence.

A series of fluorescent nanocomplexes of carboxymethyl cellulose (CMC)/Terbium (Tb)- Europium (Eu) were successfully synthesized without introducing a second ligand. By adjusting the concentration of the coordinated ions, these nanocomplexes exhibit favorably visibly tunable luminescence properties with colors being able to change from green to red. The XPS analysis demonstrates the formation Tb(III)-O2- and Eu(III)-O2- between OH and COO- in CMC and Tb3+ or Eu3+ ions, which is advantage for light absorption by UV-Vis spectroscopy and fluorescence spectroscopy. The ligand CMC plays a role in coordinating with terbium and europium ions, but also serves as an energy donor to these metal ions by antenna effect. Moreover, the energy transfer also occurred from terbium ions to europium ions in CMC matrix, which is responsible for the tunable luminescence properties of these complexes.

Rapid Activation of Diazirine Biomaterials with the Blue Light Photocatalyst.

Carbene-based macromolecules are an emerging new stimuli-sensitive class of biomaterials that avoid the impediments of free radical polymerization but maintain a rapid liquid-to-biorubber transition. Activation of diazirine-grafted polycaprolactone polyol (CaproGlu) is limited to UVA wavelengths that have tissue exposure constraints and limited light intensities. For the first time, UVA is circumvented with visible light-emitting diodes at 445 nm (blue) to rapidly activate diazirine-to-carbene covalent cross-linking. Iridium photocatalysts serve to initiate diazirine, despite having little to no absorption at 445 nm. CaproGlu's liquid organic matrix dissolves the photocatalyst with no solvents required, creating a light transparent matrix. Considerable differences in cross-linking chemistry are observed in UVA vs visible/photocatalyst formulations. Empirical analysis and theoretical calculations reveal a more efficient conversion of diazirine directly to carbene with no diazoalkane intermediate detected. Photorheometry results demonstrate a correlation between shear moduli, joules light dose, and the lower limits of photocatalyst concentration required for the liquid-to-biorubber transition. Adhesion strength on ex vivo hydrated tissues exceeds that of cyanoacrylates, with a fixation strength of up to 20 kg·f·cm2. Preliminary toxicity assessment on leachates and materials directly in contact with mammalian fibroblast cells displays no signs of fibroblast cytotoxicity.

Efficiently Enantioselective Hydrogenation Photosynthesis of (R)-1-[3,5-Bis(trifluoromethyl)phenyl] ethanol over a CLEs-TiO2 Bioinorganic Hybrid Materials.

Engineering of biological pathways with man-made materials provides inspiring blueprints for sustainable drug production. (R)-1-[3,5-Bis(trifluoromethyl)phenyl]ethanol [(R)-3,5-BTPE], as an important artificial chiral intermediate for complicated pharmaceutical drugs and biologically active molecules, is often synthesized through a hydrogenation reaction of 3,5-bis(trifluoromethyl)acetophenone (3,5-BTAP), in which enantioselectivity and sufficient active hydrogen are the key to restricting the reaction. In this work, a biohybrid photocatalytic hydrogenation system based on an artificial cross-linked enzymes (CLEs)-TiO2-Cp*Rh(bpy) photoenzyme is developed through a bottom-up engineering strategy. Here, TiO2 nanotubes in the presence of Cp*Rh(bpy) are used to transform NADP+ to NADPH during the formation of chiral alcohol intermediates from the catalytic reduction of a ketone substrate by alcohol dehydrogenase CLEs. Hydrogen and electrons, provided by water and photocatalytic systems, respectively, are transferred to reduce NADP+ to NADPH via [Cp*Rh(bpy)(H2O)]2+. With the resulting NADPH, [(R)-3,5-BTPE] is synthesized using our efficient CLEs obtained from the cell lysate by nonstandard amino acid modification. Through this biohybrid photocatalytic system, the photoenzyme-catalyzed combined reductive synthesis of [(R)-3,5-BTPE] has a yield of 41.2% after reaction for 24 h and a very high enantiomeric excess value (>99.99%). In the case of reuse, this biohybrid system retained nearly 95% of its initial catalytic activity for synthesizing the above chiral alcohol. The excellent reusability of the CLEs and TiO2 nanotubes hybrid catalytic materials highlights the environmental friendliness of (R)-3,5-BTPE production.

Trinuclear Organometallic Pt-Ir-Pt Complexes: Insights into Photophysical Properties, Amino Acid Binding and Protein Sensing.

The rational synthesis of trinuclear emissive organometallic complexes with two equivalent platinum(II) centres appended to the ancillary substituted 2,2'-bipyridyl ligand of the cyclometalated iridium(III) centre is reported here. The alkynyl-platinum moiety and cyclometalated iridium(III) centres have been separated through a non-conjugated CH2 -O-CH2 linkage. The emission titration with amino acids reveals that the complexes sense free amino acids. The luminescence sensing of BSA is thus attributed to the amino acid sensing ability of the complexes and confirmed by emission anisotropy and Far-UV CD spectral study. The decrease in α-helix in the CD spectra signifies the changes in the secondary structure of protein in presence of the complexes.

Spectroscopic and computational investigations of organometallic complexation of group 12 transition metals by methanobactins from Methylocystis sp. SB2.

Methanotrophic bacteria catalyze the aerobic oxidation of methane to methanol using Cu-containing enzymes, thereby exerting a modulating influence on the global methane cycle. To facilitate the acquisition of Cu ions, some methanotrophic bacteria secrete small modified peptides known as "methanobactins," which strongly bind Cu and function as an extracellular Cu recruitment relay, analogous to siderophores and Fe. In addition to Cu, methanobactins form complexes with other late transition metals, including the Group 12 transition metals Zn, Cd, and Hg, although the interplay among solution-phase configurations, metal interactions, and the spectroscopic signatures of methanobactin-metal complexes remains ambiguous. In this study, the complexation of Zn, Cd, and Hg by methanobactin from Methylocystis sp. strain SB2 was studied using a combination of absorbance, fluorescence, extended x-ray absorption fine structure (EXAFS) spectroscopy, and time-dependent density functional theory (TD-DFT) calculations. We report changes in sample absorbance and fluorescence spectral dynamics, which occur on a wide range of experimental timescales and characterize a clear stoichiometric complexation dependence. Mercury L3-edge EXAFS and TD-DFT calculations suggest a linear model for HgS coordination, and TD-DFT suggests a tetrahedral model for Zn2+ and Cd2+. We observed an enhancement in the fluorescence of methanobactin upon interaction with transition metals and propose a mechanism of complexation-hindered isomerization drawing inspiration from the wild-type Green Fluorescent Protein active site. Collectively, our results represent the first combined computational and experimental spectroscopy study of methanobactins and shed new light on molecular interactions and dynamics that characterize complexes of methanobactins with Group 12 transition metals.

Oxoplatin-B, a cisplatin-based platinum(IV) complex with photoactive BODIPY for mitochondria specific "chemo-PDT" activity.

Oxoplatin-B, a platinum(IV) complex [Pt(NH3)2Cl2(L1)(OH)] (1) of 4-methylbenzoic acid (HL1) functionalized with 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) was prepared, characterized and its antitumor activity studied. [Pt(NH3)2Cl2(L2)(OH)] (2) of 4-methylbenzoic acid (HL2) was studied as a control. Complex 1 showed an absorption band at 500 nm (ɛ = 4.34 × 104 M-1 cm-1) and an emission band at 515 nm (λex = 488 nm, ΦF = 0.64) in 1% dimethyl sulfoxide/Dulbecco's Modified Eagle's Medium (pH = 7.2). Visible light-induced (400-700 nm) generation of singlet oxygen was evidenced from 1,3-diphenylisobenzofuran titration study. Complex 1 showed photo-induced cytotoxicity in visible light (400-700 nm, 10 J cm-2) against human breast cancer (MCF-7), cervical cancer (HeLa) and lung cancer (A549) cells (IC50: 1.1-3.8 µM) while being less toxic in normal cells. Confocal imaging showed mitochondrial localization with additional evidence from platinum content from isolated mitochondria and 5,5,6,6'-tetrachloro-1,1',3,3' tetraethylbenzimi-dazoylcarbocyanine iodide (JC-1) assay. Cellular apoptosis was observed from Annexin-V-FITC (fluorescein isothiocyanate)/propidium iodide assay.

Carbon Monoxide Inhibits Cytochrome P450 Enzymes CYP3A4/2C8 in Human Breast Cancer Cells, Increasing Sensitivity to Paclitaxel.

Paclitaxel (PTX) is a first-line treatment in breast cancer, though resistance develops quickly and frequently. Cytochrome P450 enzymes CYP3A4 and CYP2C8, which metabolically inactivate PTX in hepatic tissue, are overexpressed in malignant breast tissues. CYP3A4 expression correlates with PTX therapy failure and poor outcomes, though no direct evidence of CYP3A4 contributing to PTX sensitivity exists. Because CYP3A4/2C8 is susceptible to carbon monoxide (CO)-mediated inhibition and CO (a gaseous signaling molecule) has previously exhibited drug-sensitizing effects in cancer cells, we hypothesized that CO-mediated inhibition of CYP3A4/2C8 could lead to enhanced drug sensitivity. Using a photo-activated CO-releasing molecule, we have assessed the ability of CO to alter the pharmacokinetics of PTX in breast cancer cells via inhibition of CYP3A4/2C8 and determined that CO does enhance sensitivity of breast cancer cells to PTX. Inhibition of CYP3A4/2C8 by CO could therefore be a promising therapeutic strategy to enhance PTX response in breast cancer.

A valproic acid-modified platinum diimine complex as potential photosensitizer for photodynamic therapy.

Histone deacetylase inhibitors have often been used in combination treatment of various types of cancers due to their non-genotoxic epigenetic potential. Valproic acid (VPA) is a well-known histone deacetylase inhibitor. Conjugate of VPA with a phtoactive platinum diimine complex through an ester bond has been fabricated to potentiate the photocytotoxicity of the photosensitizer. Its capability to generate singlet oxygen, behavior in the presence of esterase, and photocytotoxicity in tumor cells have also been studied. The results revealed that the novel VPA-modified platinum diimine complex could produce singlet oxygen efficiently and release VPA in the presence of porcine liver esterase. The results also suggested that incorporation of VPA moiety into the platinum diimine complex might significantly enhance the cytotoxicity of the complex.

Exploring the potential of highly charged Ru(II)- and heteronuclear Ru(II)/Cu(II)-polypyridyl complexes as antimicrobial agents.

The antimicrobial potential of two ruthenium(II) polypyridyl complexes, [Ru(phen)2L1]2+ and [Ru(phen)2L2]2+ (phen = 1,10-phenanthroline) containing the 4,4'-(2,5,8,11,14-pentaaza[15])-2,2'-bipyridilophane (L1) and the 4,4'-bis-[methylen-(1,4,7,10-tetraazacyclododecane)]-2,2' bipyridine (L2) units, is herein investigated. These peculiar polyamine frameworks afford the formation of highly charged species in solution, influence the DNA-binding and cleavage properties of compounds, but they do not undermine their singlet oxygen sensitizing capacities, thus making these complexes attractive 1O2 generators in aqueous solution. L1 and L2 also permit to stably host Fenton -active Cu2+ ion/s, leading to the formation of mixed Ru2+/Cu2+ forms capable to further strengthen the oxidative damages to biological targets. Herein, following a characterization of the Cu2+ binding ability by [Ru(phen)2L2]2+, the water-octanol distribution coefficients, the DNA binding, cleavage and 1O2 sensitizing properties of [Ru(phen)2L2]2+ and [Cu2Ru(phen)2L2]6+ were analysed and compared with those of [Ru(phen)2L1]2+ and [CuRu(phen)2L1]4+. The antimicrobial activity of all compounds was evaluated against B. subtilis, chosen as a model for gram-positive bacteria, both under dark and upon light-activation. Our results unveil a notable phototoxicity of [Ru(phen)2L2]2+ and [Cu2Ru(phen)2L2]6+, with MIC (minimal inhibitory concentrations) values of 3.12 µM. This study highlights that the structural characteristics of polyamine ligands gathered on highly charged Ru(II)-polypyridyl complexes are versatile tools that can be exploited to achieve enhanced antibacterial strategies.

Influences of γ-ray irradiation on physico-chemical, structural, X-ray diffraction, thermal and antimicrobial activity of some γ-irradiated N',N'''-((Z)-ethane-1,2-diylidine)bis(2-aminobenzohydrazide) metal complexes.

A series of Co(II), Ni(II), Cu(II), Th(IV) and UO2(II) complexes have been synthesized from reaction of nitrogen based ligand (L) i.e. N',N'''-((Z)-ethane-1,2-diylidine)bis(2-aminobenzohydrazide)(L) with their salts. Investigation of synthesized metal complexes was achieved by using elemental analyses, magnetic moment, molar conductance, FT-IR, UV/Vis. spectroscopy, thermal techniques and 3D molecular modeling. An octahedral geometry has been suggested for all complexes except for Ni(II) complex (2) which adopted tetrahedral geometry. To through a light on the probability of structure changes with γ-irradiation, the effect of gamma irradiation on powder samples of the complexes [Co(L)Cl2].4H2O (1); [Ni2(L)(OAc)4].5H2O (2) and [Cu(L)Br2].5H2O (3) was investigated after being exposed to high energetic γ-rays at 100 kGy dose (hereafter referred to as (1A,2A,3A, respectively). Spectral, thermal, magnetic susceptibility, molar conductance and powder X-ray diffraction patterns (XRD) were performed before and after irradiation. In addition, the in vitro antimicrobial activity of the complexes against Staphylococcus aureus as Gram-positive strain, Escherichia coli as Gram-negative strain and antifungal Candida albicans was performed for both unirradiated and irradiated samples. The obtained results showed that the irradiated complexes were affected, but not greatly by the applied γ-irradiation dose.

Photoactive siderophores: Structure, function and biology.

It is well known that bacteria and fungi have evolved sophisticated systems for acquiring the abundant but biologically inaccessible trace element iron. These systems are based on high affinity Fe(III)-specific binding compounds called siderophores which function to acquire, transport, and process this essential metal ion. Many hundreds of siderophores are now known and their numbers continue to grow. Extensive studies of their isolation, structure, transport, and molecular genetics have been undertaken in the last three decades and have been comprehensively reviewed many times. In this review we focus on a unique subset of siderophores that has only been recognized in the last 20 years, namely those whose iron complexes display photoactivity. This photoactivity, which typically results in the photooxidation of the siderophore ligand with concomitant reduction of Fe(III) to Fe(II), seemingly upsets the siderophore paradigm of forming and transporting only extremely stable Fe(III) complexes into microbial cells. Here we review their structure, synthesis, photochemistry, photoproduct coordination chemistry and explore the potential biological and ecological consequences of this photoactivity.