Structural and Spectroscopic Characterization of Copper(III) Complexes and Subsequent One-Electron Oxidation Reaction and Reactivity Studies.

The formation of Cu(III) species are often invoked as the key intermediate in Cu-catalyzed organic transformation reactions. In this study, we synthesized Cu(II) (1) and Cu(III) (3) complexes supported by a bisamidate-bisalkoxide ligand consisting of an ortho-phenylenediamine (o-PDA) scaffold and characterized them through an array of spectroscopic techniques, including UV-visible, electron paramagnetic resonance, X-ray crystallography, and 1H nuclear magnetic resonance (NMR) and X-ray absorption spectroscopy. The Cu-N/O bond distances in 3 are ∼0.1 Šreduced compared to 1, implying a significant increase in 3's overall effective nuclear charge. Further, a Cu(III) complex (4) of a bisamidate-bisalkoxide ligand containing a trans-cyclohexane-1,2-diamine moiety exhibits nearly identical Cu-N/O bond distances to that of 3, inferring that the redox-active o-PDA backbone is not oxidized upon one-electron oxidation of the Cu(II) complex (1). In addition, a considerable difference in the 1s → 4p and 1s → 3d transition energy was observed in the X-ray absorption near-edge structure data of 3 vs 1, which is typical for the metal-centered oxidation process. Electrochemical measurements of the Cu(II) complex (1) in acetonitrile exhibited two consecutive redox couples at -0.9 and 0.4 V vs the Fc+/Fc reference electrode. One-electron oxidation reaction of 3 further resulted in the formation of a ligand-oxidized Cu complex (3a), which was characterized in depth. Reactivity studies of species 3 and 3a were explored toward the activation of the C-H/O-H bonds. A bond dissociation free energy (BDFE) value of ∼69 kcal/mol was estimated for the O-H bond of the Cu(II) complex formed upon transfer of hydrogen atom to 3. The study represents a thorough spectroscopic characterization of high-valent Cu complexes and sheds light on the PCET reactivity studies of Cu(III) complexes.

Characterization of Reaction Intermediates Involved in the Water Oxidation Reaction of a Molecular Cobalt Complex.

Molecular cobalt(III) complexes of bis-amidate-bis-alkoxide ligands, (Me4N)[CoIII(L1)] (1) and (Me4N)[CoIII(L2)] (2), are synthesized and assessed through a range of characterization techniques. Electrocatalytic water oxidation activity of the Co complexes in a 0.1 M phosphate buffer solution revealed a ligand-centered 2e-/1H+ transfer event at 0.99 V followed by catalytic water oxidation (WO) at an onset overpotential of 450 mV. By contrast, 2 reveals a ligand-based oxidation event at 0.9 V and a WO onset overpotential of 430 mV. Constant potential electrolysis study and rinse test experiments confirm the homogeneous nature of the Co complexes during WO. The mechanistic investigation further shows a pH-dependent change in the reaction pathway. On the one hand, below pH 7.5, two consecutive ligand-based oxidation events result in the formation of a CoIII(L2-)(OH) species, which, followed by a proton-coupled electron transfer reaction, generates a CoIV(L2-)(O) species that undergoes water nucleophilic attack to form the O-O bond. On the other hand, at higher pH, two ligand-based oxidation processes merge together and result in the formation of a CoIII(L2-)(OH) complex, which reacts with OH- to yield the O-O bond. The ligand-coordinated reaction intermediates involved in the WO reaction are thoroughly studied through an array of spectroscopic techniques, including UV-vis absorption spectroscopy, electron paramagnetic resonance, and X-ray absorption spectroscopy. A mononuclear CoIII(OH) complex supported by the one-electron oxidized ligand, [CoIII(L3-)(OH)]-, a formal CoIV(OH) complex, has been characterized, and the compound was shown to participate in the hydroxide rebound reaction, which is a functional mimic of Compound II of Cytochrome P450.

Effect of Redox-Inactive Metal Ion-Nickel(III) Interactions on the Redox Properties and Proton-Coupled Electron Transfer Reactivity.

Mononuclear nickel(II) and nickel(III) complexes of a bisamidate-bisalkoxide ligand, (NMe4)2[NiII(HMPAB)] (1) and (NMe4)[NiIII(HMPAB)] (2), respectively, have been synthesized and characterized by various spectroscopic techniques including X-ray crystallography. The reaction of redox-inactive metal ions (Mn+ = Ca2+, Mg2+, Zn2+, Y3+, and Sc3+) with 2 resulted in 2-Mn+ adducts, which was assessed by an array of spectroscopic techniques including X-ray absorption spectroscopy (XAS), electron paramagnetic resonance (EPR), and reactivity studies. The X-ray structure of Ca2+ coordinated to Ni(III) complexes, 2-Ca2+T, was determined and exhibited an average Ni-Ca distance of 3.1253 Å, close to the metal ions' covalent radius. XAS analysis of 2-Ca2+ and 2-Y3+ in solution further revealed an additional coordination to Ca and Y in the 2-Mn+ adducts with shortened Ni-M distances of 2.15 and 2.11 Å, respectively, implying direct bonding interactions between Ni and Lewis acids (LAs). Such a short interatomic distance between Ni(III) and M is unprecedented and was not observed before. EPR analysis of 2 and 2-Mn+ species, moreover, displayed rhombic signals with gav > 2.12 for all complexes, supporting the +III oxidation state of Ni. The NiIII/NiII redox potential of 2 and 2-Mn+ species was determined, and a plot of E1/2 of 2-Mn+ versus pKa of [M(H2O)n]m+ exhibited a linear relationship, implying that the NiIII/NiII potential of 2 can be tuned with different redox-inactive metal ions. Reactivity studies of 2 and 2-Mn+ with different 4-X-2,6-ditert-butylphenol (4-X-DTBP) and other phenol derivatives were performed, and based on kinetic studies, we propose the involvement of a proton-coupled electron transfer (PCET) pathway. Analysis of the reaction products after the reaction of 2 with 4-OMe-DTBP showed the formation of a Ni(II) complex (1a) where one of the alkoxide arms of the ligand is protonated. A pKa value of 24.2 was estimated for 1a. The reaction of 2-Mn+ species was examined with 4-OMe-DTBP, and it was observed that the k2 values of 2-Mn+ species increase by increasing the Lewis acidity of redox-inactive metal ions. However, the obtained k2 values for 2-Mn+ species are much lower compared to the k2 value for 2. Such a variation of PCET reactivity between 2 and 2-Mn+ species may be attributed to the interactions between Ni(III) and LAs. Our findings show the significance of the secondary coordination sphere effect on the PCET reactivity of Ni(III) complexes and furnish important insights into the reaction mechanism involving high-valent nickel species, which are frequently invoked as key intermediates in Ni-mediated enzymatic reactions, solar-fuel catalysis, and biomimetic/synthetic transformation reactions.

Electrocatalytic Water Oxidation Activity of Molecular Copper Complexes: Effect of Redox-Active Ligands.

Two molecular copper(II) complexes, (NMe4)2[CuII(L1)] (1) and (NMe4)2[CuII(L2)] (2), ligated by a N2O2 donor set of ligands [L1 = N,N'-(1,2-phenylene)bis(2-hydroxy-2-methylpropanamide), and L2 = N,N'-(4,5-dimethyl-1,2-phenylene)bis(2-hydroxy-2-methylpropanamide)] have been synthesized and thoroughly characterized. An electrochemical study of 1 in a carbonate buffer at pH 9.2 revealed a reversible copper-centered redox couple at 0.51 V, followed by two ligand-based oxidation events at 1.02 and 1.25 V, and catalytic water oxidation at an onset potential of 1.28 V (overpotential of 580 mV). The electron-rich nature of the ligand likely supports access to high-valent copper species on the CV time scale. The results of the theoretical electronic structure investigation were quite consistent with the observed stepwise ligand-centered oxidation process. A constant potential electrolysis experiment with 1 reveals a catalytic current density of >2.4 mA cm-2 for 3 h. A one-electron-oxidized species of 1, (NMe4)[CuIII(L1)] (3), was isolated and characterized. Complex 2, on the contrary, revealed copper and ligand oxidation peaks at 0.505, 0.90, and 1.06 V, followed by an onset water oxidation (WO) at 1.26 V (overpotential of 560 mV). The findings show that the ligand-based oxidation reactions strongly depend upon the ligand's electronic substitution; however, such effects on the copper-centered redox couple and catalytic WO are minimal. The energetically favorable mechanism has been established through the theoretical calculation of stepwise reaction energies, which nicely explains the experimentally observed electron transfer events. Furthermore, as revealed by the theoretical calculations, the O-O bond formation process occurs through a water nucleophilic attack mechanism with an easily accessible reaction barrier. This study demonstrates the importance of redox-active ligands in the development of molecular late-transition-metal electrocatalysts for WO reactions.

Electrochemical Properties and Reactivity Study of [MnV(O)(µ-OR-Lewis Acid)] Cores.

A mononuclear manganese(V) oxo complex of a bis(amidate)bis(alkoxide) ligand, (NMe4)[MnV(HMPAB)(O)] [2; H4HMPAB = 1,2-bis(2-hydroxy-2-methylpropanamido)benzene], was synthesized and structurally characterized. A Mn-Oterm distance of 1.566(4) Å was observed in the solid-state structure of 2, consistent with the Mn≡O formulation. The reaction of redox-inactive metal ions (Mn+ = Li+, Ca2+, Mg2+, Y3+, and Sc3+) with 2 resulted in the formation of 2-Mn+ species, which were characterized by UV-vis, 1H NMR, cyclic voltammetry, and in situ IR spectroscopy. Theoretical calculations suggested that the alkoxide oxygen atoms of the ligand scaffold are energetically most favorable for coordinating the Mn+ ions in 2. Complex 2 revealed one-electron-reduction potential at -0.01 V versus ferrocenium/ferrocene, which shifted anodically upon coordination of Mn+ ions to 2, and such a shift became more prominent with stronger Lewis acids. The oxygen-atom transfer (OAT) reactivities of 2 and 2-Mn+ species with triphenylphosphine were compared, which exhibited a systematic increase of the reaction rate with increasing Lewis acidity of Mn+ ions, and a plot of log k2 versus Lewis acidity of Mn+ ions (ΔE) followed a linear relationship. It was observed that 2-Sc3+ was ca. 3200 times more reactive toward the OAT reaction compared to 2. Hammett analysis of 2 exhibited a V-shaped plot, indicating a change of the reaction mechanism upon going from electron-rich to electron-deficient Ar3P substrates. In contrast, 2-Ca2+ and 2-Sc3+ showed an electrophilic nature toward the OAT reaction, thus demonstrating the role of the Lewis acid in controlling the OAT mechanism. The hydrogen-atom abstraction reaction of 2 and 2-Mn+ adducts with 1-benzyl-1,4-dihydronicotinamide was investigated, and it was observed that the rate of reaction did not vary considerably with the Lewis acidity of Mn+ ions. On the basis of Eyring analysis of 2 and 2-Mn+ adducts, we hypothesized an entropy-controlled hydrogen-atom-transfer reaction for 2-Sc3+, which is different from the reaction mechanism of 2 and 2-Ca2+.

Characterization and reactivity study of non-heme high-valent iron-hydroxo complexes.

A terminal FeIIIOH complex, [FeIII(L)(OH)]2- (1), has been synthesized and structurally characterized (H4L = 1,2-bis(2-hydroxy-2-methylpropanamido)benzene). The oxidation reaction of 1 with one equiv. of tris(4-bromophenyl)ammoniumyl hexachloroantimonate (TBAH) or ceric ammonium nitrate (CAN) in acetonitrile at -45 °C results in the formation of a FeIIIOH ligand radical complex, [FeIII(L˙)(OH)]- (2), which is hereby characterized by UV-visible, 1H nuclear magnetic resonance, electron paramagnetic resonance, and X-ray absorption spectroscopy techniques. The reaction of 2 with a triphenylcarbon radical further gives triphenylmethanol and mimics the so-called oxygen rebound step of Cpd II of cytochrome P450. Furthermore, the reaction of 2 was explored with different 4-substituted-2,6-di-tert-butylphenols. Based on kinetic analysis, a hydrogen atom transfer (HAT) mechanism has been established. A pK a value of 19.3 and a BDFE value of 78.2 kcal/mol have been estimated for complex 2.

Study of salivary gland lesions with fine needle aspiration cytology and histopothology along with immunohistochemistry.

Salivary gland swelling is a common and important problem. Acute and chronic sialadenitis, different benign and malignant neoplasms are the common causes which present with salivary gland swelling. Imaging technique is not so helpful in pre-operative diagnosis; microscopical examination is required for diagnosis. Pre-operative core needle biopsy is hazardous and may damage facial nerve, lead to fistula formation or associated with tumour seeding. Fine needle aspiration cytology (FNAC) is however virtually risk-free. The study was done to assess the utility of FNAC and its accuracy and pitfalls with respect to histopathology and advantages of immunohistochemistry. The study was done with 40 cases of salivary gland swelling. After clinical examination, FNAC and histopathological examination along with immunohistochemistry was done and the results were correlated. Out of 40 cases, 25 involved the parotid gland, most common age group affected was 20 - 40 years and male: female ratio was 5: 3. Out of 40 cases 37 cases were cytologically and histopathologically correlated and rest 3 cases were different. Among these 3 cases, 2 were adenoid cystic carcinoma which was cytologically diagnosed as benign neoplasm (monomorphic adenoma). One case of Warthin's tumour was cytologically diagnosed as pleomorphic adenoma. The sensitivity of this study was found to be 71.43%, specificity 100% and accuracy was 93.10%. This study corroborates well with other studies including immunohistochemical findings. p53 expression was found to be related with nature of the neoplasm. FNAC is an important tool for early diagnosis of salivary gland lesions.