Novel iron(III) complexes of tripodal and linear tetradentate bis(phenolate) ligands: close relevance to intradiol-cleaving catechol dioxygenases

Four new iron(III) complexes of the bis(phenolate) ligands N,N-dimethyl-N',N'-bis(2-hydroxy-3,5-dimethylbenzyl)ethylenediamine [H2(L1)], N,N-dimethyl-N',N'-bis(2-hydroxy-4-nitrobenzyl)ethylenediamine [H2(L2)], N,N'-dimethyl-N,N'-bis(2-hydroxy-3,5-dimethylbenzyl)ethylenediamine [H2(L3)], and N,N'-dimethyl-N,N'-bis(2-hydroxy-4-nitrobenzyl)ethylenediamine [H2(L4)] have been isolated and studied as structural and functional models for the intradiol-cleaving catechol 1,2-dioxygenases (CTD). The complexes [Fe(L1)Cl] (1), [Fe(L2)(H2O)Cl] (2), [Fe(L3)Cl] (3), and [Fe(L4)(H2O)Cl] (4) have been characterized using absorption spectral and electrochemical techniques. The single-crystal X-ray structures of the ligand H2(L1) and the complexes 1 and 2 have been successfully determined. The tripodal ligand H2(L1) containing a N2O2 donor set represents the metal-binding region of the iron proteins. Complex 1 contains an FeN2O2Cl chromophore with a novel trigonal bipyramidal coordination geometry. While two phenolate oxygens and an amine nitrogen constitute the trigonal plane, the other amine nitrogen and chloride ion are located in the axial positions. In contrast, 2 exhibits a rhombically distorted octahedral coordination geometry for the FeN2O3Cl chromophore. Two phenolate oxygen atoms, an amine nitrogen atom, and a water molecule are located on the corners of a square plane with the axial positions being occupied by the other nitrogen atom and chloride ion. The interaction of the complexes with a few monodentate bases and phenolates and differently substituted catechols have been investigated using absorption spectral and electrochemical methods. The effect of substituents on the phenolate rings on the electronic spectral features and FeIII/FeII redox potentials of the complexes are discussed. The interaction of the complexes with catecholate anions reveals changes in the phenolate to iron(III) charge-transfer band and also the appearance of a low-energy catecholate to iron(III) charge-transfer band similar to catechol dioxygenase-substrate complexes. The redox behavior of the 1:1 adducts of the complexes with 3,5-di-tert-butylcatechol (H2DBC) has been also studied. The reactivities of the present complexes with H2DBC have been studied and illustrated. Interestingly, only 2 and 4 catalyze the intradiol-cleavage of H2DBC, the rate of oxygenation being much faster for 4. Also 2, but not 4, yields an extradiol cleavage product. The reactivity of the complexes could be illustrated not on the basis of the Lewis acidity of the complexes alone but by assuming that the product release is the rate-determining phase of the catalytic reaction.     

Carboxysome-Inspired Electrocatalysis using Enzymes for the Reduction of CO2 at Low Concentrations**

The electrolysis of dilute CO₂ streams suffers from low concentrations of dissolved substrate and its rapid depletion at the electrolyte-electrocatalyst interface. These limitations require first energy-intensive CO₂ capture and concentration, before electrolyzers can achieve acceptable performances. For direct electrocatalytic CO₂ reduction from low-concentration sources, we introduce a strategy that mimics the carboxysome in cyanobacteria by utilizing microcompartments with nanoconfined enzymes in a porous electrode. A carbonic anhydrase accelerates CO₂ hydration kinetics and minimizes substrate depletion by making all dissolved carbon available for utilization, while a highly efficient formate dehydrogenase reduces CO₂ cleanly to formate; down to even atmospheric concentrations of CO₂. This bio-inspired concept demonstrates that the carboxysome provides a viable blueprint for the reduction of low-concentration CO₂ streams to chemicals by using all forms of dissolved carbon.     

Isolation of Sesquiterpene Lactones and the Antioxidant and Anticancer Activities of Crude Extracts from Cyanthillium cinereum

Chemistry of Natural Compounds - Three sesquiterpene lactones has been isolated from Cyanthillium cinereum (L.) H. Rob. by bioactivity guided assay and characterized by spectral methods as...     

Iron(III) complexes of certain tetradentate phenolate ligands as functional models for catechol dioxygenases

Catechol 1,2-dioxygenase (CTD) and protocatechuate 3,4-dioxygenase (PCD) are bacterial non-heme iron enzymes, which catalyse the oxidative cleavage of catechols tocis, cis-muconic acids with the incorporation of molecular oxygen via a mechanism involving a high-spin ferric centre. The iron(III) complexes of tripodal phenolate ligands containing N₃O and N₂O₂ donor sets represent the metal binding region of the iron proteins. In our laboratory iron(III) complexes of mono- and bisphenolate ligands have been studied successfully as structural and functional models for the intradiol-cleaving catechol dioxygenase enzymes. The single crystal X-ray crystal structures of four of the complexes have been determined. One of thebis-phenolato complexes contains a FeN₂O₂Cl chromophore with a novel trigonal bipyramidal coordination geometry. The Fe-O-C bond angle of 136.1‡ observed for one of the iron(III) complex of a monophenolate ligand is very similar to that in the enzymes. The importance of the nearby sterically demanding coordinated -NMe₂ group has been established and implies similar stereochemical constraints from the other ligated amino acid moieties in the 3,4-PCD enzymes, the enzyme activity of which is traced to the difference in the equatorial and axial Fe-O(tyrosinate) bonds (Fe-O-C, 133, 148‡). The nature of heterocyclic rings of the ligands and the methyl substituents on them regulate the electronic spectral features, Fe^III/Fe^II redox potentials and catechol cleavage activity of the complexes. Upon interacting with catecholate anions, two catecholate to iron(III) charge transfer bands appear and the low energy band is similar to that of catechol dioxygenase-substrate complex. Four of the complexes catalyze the oxidative cleavage of H₂DBC by molecular oxygen to yield intradiol cleavage products. Remarkably, the more basic N-methylimidazole ring in one of the complexes facilitates the rate-determining productreleasing phase of the catalytic reaction. The present study provides support to the novel substrate activation mechanism proposed for the intradiol-cleavage enzymes.     

Leveraging γ‐Glutamyl Transferase To Direct Cytotoxicity of Copper Dithiocarbamates against Prostate Cancer Cells

A prodrug approach is presented to direct copper‐dependent cytotoxicity to prostate cancer cells. The prochelator GGTDTC requires activation by γ‐glutamyl transferase (GGT) to release the metal chelator diethyldithiocarbamate from a linker that masks its thiol reactivity and metal binding properties. In vitro studies demonstrated successful masking of copper binding as well as clean liberation of the chelator by GGT. GGTDTC was stable to non‐specific degradation when incubated with a series of prostate cancer and normal cell lines, with selective release of diethyldithiocarbamate only occurring in cells with measurable GGT activity. The antiproliferative efficacy of the prochelator correlated with cellular GGT activity, with 24 h inhibitory concentrations ranging from 800 nm in prostate cancer lines 22Rv1 and LNCaP to over 15 μm in normal prostate PWR‐1E cells. These findings underscore a new strategy to leverage the amplified copper metabolism of prostate cancer by conditional activation of a metal‐binding pharmacophore.     

A study on the seasonal variation of the essential oil composition from Plectranthus hadiensis and its antibacterial activity

The chemical composition and seasonal variation of the essential oil from the aerial parts of Plectranthus hadiensis grown during the rainy and summer seasons in the Western Ghats of India was analysed by GC–MS technique. The analysis of rainy season oil led to the identification of 31 compounds, representing 96.4% of the essential oil and the winter season oil led to 25 compounds, representing 95.1% of the oil. Most of the compounds were sesquiterpenes and oxygenated monoterpenes. The major components of the rainy season oil were L-fenchone (30.42%), β-farnesene (11.87%), copaene(11.10%), 2,3-dimethyl hydroquinone (10.78%), α-caryophyllene(8.41%) and piperitone oxide (3.94%) and of the summer season oil are L-fenchone (31.55%), copaene(11.93%), β-farnesene (10.45%), 1,8-naphthalenedione, 8a-ethylperhydro (10.06%), α-caryophyllene(6.36%), piperitone oxide (5.79%) and limonene(4.63%). Antibacterial activity of the essential oil of P. hadiensis was tested using zone of inhibition and minimum inhibition concentration methods. Both the oils inhibited the organisms and showed the zone of inhibition in the range of 20–35 mm with MIC values between 32 and 64 mg/dL.     

Threshold conditions and bound states for locally periodic delta potentials

We present a systematic study of the conditions for the generation of threshold energy eigen states and also the energy spectrum generated by two types of locally periodic delta potentials each having the same strength λV and separation distance parameter a: (a) sum of N attractive potentials and (b) sum of pairs of attractive and repulsive potentials. Using the dimensionless parameter g = λV a in case (a) the values of g = g _n , n = 1, 2, …, N at which threshold energy bound state gets generated are shown to be the roots of Nth order polynomial D ₁(N, g) in g. We present an algebraic recursive procedure to evaluate the polynomial D ₁(N, g) for any given N. This method obviates the need for the tedious mathematical analysis described in our earlier work to generate D ₁(N, g). A similar study is presented for case (b). Using the properties of D ₁(N, g) we establish that in case (a) the critical minimum value of g which guarantees the generation of the maximum possible number of bound states is g = 4. The corresponding result for case (b) is g = 2. A typical set of numerical results showing the pattern of variation of g _n as a function of n and several interesting features of the energy spectrum for different values of g and N are also described.     

Open-mouthed metallic microcapsules: exploring performance improvements at agglomeration-free interiors

Although artificial capsule structures have been thoroughly investigated, functionality at the surfaces of their interiors has been surprisingly overlooked. In order to exploit this aspect of capsular structure, we here report the breakthrough fabrication of metallic (platinum) microcapsules with sufficient accessibility and electroactivity at both interior and exterior surfaces (open-mouthed platinum microcapsules), and also we demonstrate improvements in electrochemical and catalytic functions to emphasize the practical importance of our concept. The open-mouthed platinum microcapsules were prepared by template synthesis using polystyrene spheres, where surface-fused crystalline nanoparticles formed a capsule shell. Subsequent removal of the polystyrene spheres induced formation of mouth-like openings. The open-mouthed platinum microcapsules exhibit a substantial increase of their electrode capability for methanol oxidation and catalytic activities for carbon monoxide (CO) oxidation. Notably, activity loss during CO oxidation due to undesirable particle agglomeration can be drastically suppressed using the open-mouthed microcapsules.