Inorganics, Volume 7, Issue 1 (January 2019) – 11 articles

We report the synthesis and characterization of [Cu(P^P)(N^S)][PF₆] complexes with P^P = bis(2-(diphenylphosphino)phenyl) ether (POP) or 4,5-bis(diphenylphosphino)-9,9- dimethylxanthene (xantphos) and N^S = 2-(iso-propylthio)pyridine (iPrSpy) or 2-(tert-butylthio)pyridine (tBuSpy). The single crystal structures of [Cu(POP)(iPrSPy)][PF₆] and [Cu(POP)(tBuSPy)][PF₆] have been determined and confirm a distorted tetrahedral copper(I) centre and chelating P^P and N^S ligands in each complex. Variable temperature (VT) ¹H and ³¹P{¹H} NMR spectroscopy reveals dynamic behavior with motion of the POP backbone in [Cu(POP)(iPrSPy)][PF₆] and [Cu(POP)(tBuSPy)][PF₆] frozen out at 238 K. VT NMR spectroscopic data including EXSY peaks in the ROESY spectrum of [Cu(xantphos)(tBuSPy)][PF₆] at 198 K reveal that two conformers exist in an approximate ratio of 5:1. Replacing bpy by the N^S ligands shifts the Cu⁺/Cu²⁺ oxidation to a higher potential. The copper(I) compounds are weak emitters in the solid state with PLQY values of <2%. These values are similar to those for [Cu(POP)(bpy)][PF₆] and [Cu(xantphos)(bpy)][PF₆] in the solid state. Full article

Magnetic resonance imaging (MRI) is a powerful non-invasive diagnostic tool that can provide important insights for medical treatment monitoring and optimization. Photodynamic therapy (PDT), a minimally invasive treatment for various types of tumors, is drawing increasing interest thanks to its temporal and spatial selectivity. The combination of MRI and PDT offers real-time monitoring of treatment and can give significant information for drug-uptake and light-delivery parameters optimization. In this review we will give an overview of molecular theranostic agents that have been designed for their potential application in MRI and PDT. Full article

We have theoretically studied the formation of hydrogen-bonded (HB) and halogen-bonded (XB) complexes of halogen oxoacids (HXO_n) with Lewis bases (NH₃ and Cl⁻) at the CCSD(T)/CBS//RIMP2/aug-cc-pVTZ level of theory. Minima structures have been found for all HB and XB systems. Proton transfer is generally observed in complexes with three or four oxygen atoms, namely, HXO₄:NH₃, HClO₃:Cl⁻, HBrO₃:Cl⁻, and HXO₄:Cl⁻. All XB complexes fall into the category of halogen-shared complexes, except for HClO₄:NH₃ and HClO₄:Cl⁻, which are traditional ones. The interaction energies generally increase with the number of O atoms. Comparison of the energetics of the complexes indicates that the only XB complexes that are more favored than those of HB are HIO:NH₃, HIO:Cl⁻, HIO₂:Cl⁻, and HIO₃:Cl⁻. The atoms-in-molecules (AIM) theory is used to analyze the complexes and results in good correlations between electron density and its Laplacian values with intermolecular equilibrium distances. The natural bon orbital (NBO) is used to analyze the complexes in terms of charge-transfer energy contributions, which usually increase as the number of O atoms increases. The nature of the interactions has been analyzed using the symmetry-adapted perturbation theory (SAPT) method. The results indicate that the most important energy contribution comes from electrostatics, followed by induction. Full article

The enzyme nitrogenase naturally hydrogenates N₂ to NH₃, achieved through the accumulation of H atoms on FeMo-co, the Fe₇MoS₉C(homocitrate) cluster that is the catalytically active site. Four intermediates, E₁H₁, E₂H₂, E₃H₃, and E₄H₄, carry these hydrogen atoms. I report density functional calculations of the numerous possibilities for the geometric and electronic structures of these poly-hydrogenated forms of FeMo-co. This survey involves more than 100 structures, including those with bound H₂, and assesses their relative energies and most likely electronic states. Twelve locations for bound H atoms in the active domain of FeMo-co, including Fe–H–Fe and Fe–H–S bridges, are studied. A significant result is that transverse Fe–H–Fe bridges (transverse to the pseudo-threefold axis of FeMo-co and shared with triply-bridging S) are not possible geometrically unless the S is hydrogenated to become doubly-bridging. The favourable Fe–H–Fe bridges are shared with doubly-bridging S. ENDOR data for an E₄H₄ intermediate trapped at low temperature, and interpretations in terms of the geometrical and electronic structure of E₄H₄, are assessed in conjunction with the calculated possibilities. The results reported here yield a set of 24 principles for the mechanistically significant coordination chemistry of H and H₂ on FeMo-co, in the stages prior to N₂ binding. Full article

Tetrazolato-bridged dinuclear platinum(II) complexes ([{cis-Pt(NH₃)₂}₂(μ-OH)(μ-5-R-tetrazolato-N2,N3)]²⁺; tetrazolato-bridged complexes) are a promising source of next-generation platinum-based drugs. β-Cyclodextrin (β-CD) forms inclusion complexes with bulky organic compounds or substituents, changing their polarity and molecular dimensions. Here, we determined by ¹H-NMR spectroscopy, the stability constants for inclusion complexes formed between β-CD and tetrazolato-bridged complexes with a bulky, lipophilic substituent at tetrazole C5 (complexes 1–3, phenyl, n-nonyl, and adamantyl substitution, respectively). We then determined the in vitro cytotoxicity and in vivo antitumor efficacy of complexes 1–3 against the Colon-26 colorectal cancer cell line in the absence or presence of equimolar β-CD. Compared with the platinum-based anticancer drug oxaliplatin (1R,2R-diaminocyclohexane)oxalatoplatinum(II)), complex 2 had similar cytotoxicity, complex 3 was moderately cytotoxic, and complex 1 was the least cytotoxic. The cytotoxicity of the complexes decreased in the presence of β-CD. When we examined the in vivo antitumor efficacy of complexes 1–3 (10 mg/kg) against homografted Colon-26 colorectal tumors in male BALB/c mice, they showed a relatively low tumor growth inhibition compared with oxaliplatin. However, in the presence of β-CD, complex 3 had higher in vivo antitumor efficacy than oxaliplatin, suggesting a new direction for future research into tetrazolato-bridged complexes with high in vivo antitumor activity. Full article

Cancer is known to be one of the major causes of death nowadays. Among others, chemotherapy with cisplatin is a commonly used treatment. Although widely employed, cisplatin is known to cause severe side effects, such as nerve and kidney damage, nausea, vomiting, and bone marrow suppression. Most importantly, a number of cancer tumors are acquiring resistance to cisplatin, limiting its clinical use. There is therefore a need for the discovery of novel anticancer agents. Complementary to chemotherapy, Photodynamic Therapy (PDT) has expanded the range of treatment opportunities of numerous kinds of cancer. Nonetheless, the currently approved PDT photosensitizers (PSs) suffer from major drawbacks, which include poor water solubility or photobleaching, in addition to a slow clearance from the body that causes photosensitivity. Due to these limitations, there is a need for the development of new PDT PSs. To overcome these problems, a lot of research groups around the world are currently focusing their attention towards the development of new metal complexes as PDT PSs. However, most synthesized compounds reported so far show limited use due to their poor absorption in the phototherapeutic window. Herein, we report on the preparation and characterization of three Fe(II) polypyridine complexes (4–6) and evaluate their potential as both anticancer agents and PDT PSs. Very importantly, these compounds are stable in human plasma, photostable upon continuous LED irradiation, and absorb in the red region of the spectrum. We could demonstrate that through additional sulfonic acid groups on the polypyridine ligand being used (bphen: 4,7-diphenyl-1,10-phenanthroline), the water solubility of the complexes could be highly improved, whereas the photophysical properties did not significantly change. One of these complexes (4) shows interesting toxicity, with IC₅₀ values in the low micromolar range in the dark as well as some phototoxicity upon irradiation at 480 and 540 nm against RPE-1 and HeLa cells. Full article

The synthesis, characterization and reactivity of several bi- and tridentate, N-ligated manganese carbonyl trifluoromethyl complexes are presented. These complexes exhibit elongated Mn–C_CF3 bonds (versus Mn(CF₃)(CO)₅), suggesting a lability that could be utilized for the transfer or insertion of the CF₃ functional group into organic substrates. Unlike their Mn–X congeners (X = Cl, Br), these Mn–CF₃ complexes exhibit a preference for hard donor ancillary ligands, thus enabling the synthesis of 4 N-ligated Mn–CF₃ complexes including a mixed-donor tridentate complex using an NNS Schiff base ([2-(methylthio)-N-(1-(pyridin-2-yl)ethylidene)aniline]). Although we have not yet identified efficient CF₃ transfer reactions, fluoride abstraction from the Mn–CF₃ complexes using trimethylsilyl triflate affords the first stable Mn fluorocarbenes as evidenced by ¹⁹F NMR spectroscopy. Full article

Since the discovery of cisplatin and its potency in anticancer therapy, the development of metallodrugs has been an active area of research. The large choice of transition metals, oxidation states, coordinating ligands, and different geometries, allows for the design of metal-based agents with unique mechanisms of action. Many metallodrugs, such as titanium, ruthenium, gallium, tin, gold, and copper-based complexes have been found to have anticancer activities. However, biological application of these agents necessitates aqueous solubility and low systemic toxicity. This minireview highlights the emerging strategies to facilitate the in vivo application of metallodrugs, aimed at enhancing their solubility and bioavailability, as well as improving their delivery to tumor tissues. The focus is on encapsulating the metal-based complexes into nanocarriers or coupling to biomacromolecules, generating efficacious anticancer therapies. The delivery systems for complexes of platinum, ruthenium, copper, and iron are discussed with most recent examples. Full article

The HIV nucleocapsid protein NCp7 was previously shown to play a number of roles in the viral life cycle and was previously identified as a potential target for small molecule intervention. In this work, the synthesis of the previously unreported complexes [Au(dien)(1MeCyt)]³⁺, [Au(N-Medien)(1MeCyt)]³⁺, and [Au(dien)(Cyt)]³⁺ is detailed, and the interactions of these complexes with the models for NCp7 are described. The affinity for these complexes with the target interaction site, the “essential” tryptophan of the C-terminal zinc finger motif of NCp7, was investigated through the use of a fluorescence quenching assay and by ¹H-NMR spectroscopy. The association of [Au(dien)(1MeCyt)]³⁺ as determined through fluorescence quenching is intermediate between the previously reported DMAP and 9-EtGua analogs, while the associations of [Au(N-Medien)(1MeCyt)]³⁺ and [Au(dien)(Cyt)]³⁺ are lower than the previously reported complexes. Additionally, NMR investigation shows that the self-association of relevant compounds is negligible. The specifics of the interaction with the C-terminal zinc finger were investigated by circular dichroism spectroscopy and electrospray-ionization mass spectrometry. The interaction is complete nearly immediately upon mixing, and the formation of Au_xFⁿ⁺ (x = 1, 2, or 4; F = apopeptide) concomitant with the loss of all ligands is observed. Additionally, oxidized dimerized peptide was observed for the first time as a product, indicating a reaction via a charge transfer mechanism. Full article