Mohan Bhadbhade

Sulfonate protecting groups. Regioselective sulfonylation of myo-inositol orthoesters-improved synthesis of precursors of D- and L-myo-inositol 1,3,4,5-tetrakisphosphate, myo-inositol 1,3,4,5,6-pentakisphosphate and related derivatives.

The regioselectivity of sulfonylation of myo-inositol orthoesters was controlled by the use of different bases to obtain the desired sulfonate. Monosulfonylation of myo-inositol orthoesters in the presence of one equivalent of sodium hydride or triethylamine resulted in the sulfonylation of the 4-hydroxyl group. The use of pyridine as a base for the same reaction resulted in sulfonylation of the 2-hydroxyl group. Disulfonylation of these orthoesters in the presence of excess sodium hydride yielded the 4,6-di-O-sulfonylated orthoesters. However, the use of triethylamine or pyridine instead of sodium hydride yielded the 2,4-di-O-sulfonylated orthoester. Sulfonylated derivatives of myo-inositol orthoesters were stable to conditions of O-alkylation but were cleaved using magnesium/methanol or sodium methoxide in methanol to regenerate the corresponding myo-inositol orthoester derivative. These new methods of protection-deprotection have been used: (i) for the efficient synthesis of enantiomers of 2,4-di-O-benzyl-myo-inositol, which are precursors for the synthesis of D- and L-myo-inositol 1,3,4,5-tetrakisphosphate; (ii) for the preparation of 2-O-benzyl-myo-inositol which is a precursor for the preparation of myo-inositol 1,3,4,5,6-pentakisphosphate.

Hybrid cyclic peptide–thiourea cryptands for anion recognition

Two cyclic peptide derived cryptands incorporating thioureas in the framework were synthesised as neutral anion receptors and bind acetate ions with high affinity and, in one case, good selectivity.

Novel phenazine crystals enable direct electron transfer to methanogens in anaerobic digestion by redox potential modulation

With one billion tons of methane produced annually by microorganisms, biogas production can be appreciated both for its role in global organic matter turnover and as an energy source for humankind. The importance of electron transfer from electrically conductive surfaces or from bacteria to methanogenic Archaea has been implicated in widespread commercial anaerobic digestion processes, though a mechanism for reception of electrons from conductive surfaces or pili by methanogens has never been demonstrated. Here we describe a novel crystalline form of the synthetic phenazine neutral red that harvests electrons from reduced inorganic and organic microbial sources in anaerobic environments and makes them available to methanogenic Archaea. The novel crystalline form is so effective at harvesting reducing equivalents because it displays a potential for reduction 444 mV higher than the soluble form (E′ = 70 mV). Neutral red molecules solubilised in the reduced state by protonation at the point of methanogen cell contact with the crystal surface deliver electrons to methanogens at a negative midpoint potential (E′ = −375 mV). We demonstrate that soluble neutral red delivers reducing equivalents directly to the membrane bound HdrED heterodisulfide reductase of Methanosarcina, replenishing the CoM-SH and CoB-SH pool for methanogenesis and generating proton motive force. An order of magnitude increase in methane production is recorded in pure acetate fed Methanosarcina and coal and food waste fed mixed cultures in the laboratory. The phenomenon is also demonstrated at field scale in a sub-bituminous coal seam 80 m below ground level.

Hemilabile and bimetallic coordination in Rh and Ir complexes of NCN pincer ligands.

Two new pincer ligands have been developed that contain a central N-heterocyclic carbene (NHC) moiety linked to two pendant pyrazole groups by either a methylene (NCN(me)) or ethylene (NCN(et)) chain. The coordination of these two ligands to rhodium and iridium resulted in a variety of binding modes. Tridentate coordination of the ligands was observed in the complexes [Rh(NCN(me))(COD)]BPh4 (8), [Ir(NCN(me))(COD)]BPh4 (10), [Rh(NCN(et))(CO)2]BPh4 (13), and [Ir(NCN(me))(CO)2]BPh4 (14), and monodentate NHC coordination was observed for [Ir(NCN(me))2(COD)]BPh4 (11) and [Ir(NCN(et))2(COD)]BPh4 (12). Both tridentate and bidentate coordination modes were characterized for [Rh(NCN(et))(COD)]BPh4 (9) in the solution and solid state, respectively, while an unusual bridging mode was observed for the bimetallic complex [Rh(μ-NCN(me))(CO)]2(BPh4)2 (15). The impact of this diverse coordination chemistry on the efficiency of the complexes as catalysts for the addition of NH, OH, and SiH bonds to alkynes was explored.

Cationic Rh and Ir complexes containing bidentate imidazolylidene–1,2,3-triazole donor ligands: synthesis and preliminary catalytic studies

A series of new cationic Rh(I), Rh(III) and Ir(III) complexes containing hybrid bidentate N-heterocyclic carbene–1,2,3-triazolyl donor of general formulae [Rh(CaT)(COD)]BPh4 (2a–d), [Rh(CaT)(CO)2]BPh4 (3a–d) and [M(CaT)(Cp*)Cl]BPh4 (M = Rh, 4a–d; M = Ir, 5a–c), where CaT = bidentate N-heterocyclic carbene–triazolyl ligands, COD = 1,5-cyclooctadiene and Cp* = 1,2,3,4,5-pentamethylcyclopentadienyl, were synthesised. The imidazolium–1,2,3-triazolyl pre-ligands (1a–c and 1e–i) were readily prepared using the Cu(I) catalysed ‘click reaction’ between phenyl azide or benzyl azides with propargyl functionalised imidazolium salts. The single crystal solid state structures of complexes 2a–d; 3a–b; 4a–d and 5a–b confirm the bidentate coordination of the NHC–1,2,3-triazolyl ligand with the NHC coordinating via the ‘normal’ C2-carbon and the 1,2,3-triazolyl donor coordinating via the N3′ atom to form six membered metallocycles. These complexes are the first examples of Rh and Ir complexes containing the hybrid NHC–1,2,3-triazolyl ligands which exhibit a bidentate coordination mode. A number of these complexes showed limited efficiency as catalysts for the intramolecular hydroamination of 4-pentyn-1-amine to 2-methylpyrroline.

A Capped Dipeptide Which Simultaneously Exhibits Gelation and Crystallization Behavior

Short peptides capped at their N-terminus are often highly efficient gelators, yet notoriously difficult to crystallize. This is due to strong unidirectional interactions within fibers, resulting in structure propagation only along one direction. Here, we synthesize the N-capped dipeptide, benzimidazole-diphenylalanine, which forms both hydrogels and single crystals. Even more remarkably, we show using atomic force microscopy the coexistence of these two distinct phases. We then use powder X-ray diffraction to investigate whether the single crystal structure can be extrapolated to the molecular arrangement within the hydrogel. The results suggest parallel β-sheet arrangement as the dominant structural motif, challenging existing models for gelation of short peptides, and providing new directions for the future rational design of short peptide gelators.

Low Oxidation State Iron(0), Iron(I), and Ruthenium(0) Dinitrogen Complexes with a Very Bulky Neutral Phosphine Ligand

The synthesis of a series of iron and ruthenium complexes with the ligand P(2)P3(Cy), P(CH2CH2PCy2)3 is described. The iron(0) and ruthenium(0) complexes Fe(N2)(P(2)P3(Cy)) (1) and Ru(N2)(P(2)P3(Cy)) (2) were synthesized by treatment of [FeCl(P(2)P3(Cy))](+) and [RuCl(P(2)P3(Cy))](+) with an excess of potassium graphite under a nitrogen atmosphere. The Fe(I) and Ru(I) species [Fe(N2)(P(2)P3(Cy))](+) (3) and RuCl(P(2)P3(Cy)) (4) were synthesized by treatment of [FeCl(P(2)P3(Cy))](+) and [RuCl(P(2)P3(Cy))](+) with 1 equiv of potassium graphite under a nitrogen atmosphere. The cationic dinitrogen species [Fe(N2)H(P(2)P3(Cy))](+) (6) and [Ru(N2)H(P(2)P3(Cy))](+) (7) were formed by treatment of 1 and 3, respectively, with 1 equiv of a weak organic acid. The iron(II) complex Fe(H)2(P(2)P3(Cy)) (5) was also synthesized and characterized. Complexes [RuCl(P(2)P3(Cy))][BPh4], 1, 2, 3[BPh4], 4, 5, 6[BF4], and 7[BF4] were characterized by X-ray crystallography. The Fe(I) and Ru(I) complexes 3 and 4 were characterized by electron paramagnetic resonance (EPR) spectroscopy, and the Fe(I) complex has an EPR spectrum typical of a metal-centered radical.

Bio‐Inspired Catalytic Imine Reduction by Rhodium Complexes with Tethered Hantzsch Pyridinium Groups: Evidence for Direct Hydride Transfer from Dihydropyridine to Metal‐Activated Substrate

Herein, we report a conceptually new approach to the catalytic reduction of unsaturated substrates, demonstrated for imine hydrogenation, based on mimicry of biological processes in which hydride is directly transferred from dihydronicotinamide adenine dinucleotide (phosphate) (NAD(P)H) cofactor to an enzyme-activated substrate. NAD(P)H is Nature s hydride carrier. 3] In many (de)hydrogenase enzymes that catalyze direct hydride transfer to/ from NAD(P)/NAD(P)H, the substrate is polarized and thus activated by binding to a metal ion. Classic examples are alcohol dehydrogenases (Zn active site) and acetohydroxy acid isomeroreductase hydrogenases (with an (Mg)2 or (Mn)2 active site). [5] Our aim in this research was to prepare and test a new design for a homogeneous catalyst in which an unnatural organo-transition-metal center is tethered to an organohydride donor (OHD). The design incorporates the main features of an (de)hydrogenase enzyme and its NAD(P)H cofactor into one molecule. We envisaged that the close proximity of cofacial, linked metal and OHD centers would facilitate both regeneration of the OHD through the intermediacy of metallo-hydride species and the rapid transfer hydride from the OHD to a metal-bound, and thus activated, unsaturated substrate. We targeted a [Cp*Rh(NN)L] (NN = diimine; L = halido, n = 1; L = solvato co-ligand, n = 2) complex, as these are the most commonly used catalysts for regeneration of NAD(P)H from NAD(P). Electrolytic reduction of [Cp*Rh(NN)L] affords the corresponding Rh complex, which is rapidly protonated at low pH to give the active hydrido–Rh species for hydride transfer to NAD(P). Conveniently, catalytic regeneration of OHDs using [Cp*Rh(NN)L] can be driven directly by electricity, by light and a photosensitizer, or by renewable chemical reductants, such as formate. We employed a Hantzsch ester, such as 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate (HEH), as the OHD center, because of their wide use as mimics for NAD(P)H in transfer hydrogenations of unsaturated substrates, such as imines or enones. 11] Typically, a Brønsted or Lewis acid catalyst is required to activate the substrate and to organize it and HEH for stereoselective hydride transfer. Of note here is the recent disclosure by Zhou et al. on ruthenium-complex-catalyzed HEH regeneration using dihydrogen at high pressures for the asymmetric transfer hydrogenation of cyclic oximines catalyzed by a chiral phosphoric acid. We believed that the flexible electron source and the mild reduction conditions for [Cp*Rh(NN)L] catalysis of OHD regeneration would circumvent the demand for dihydrogen pressure and lead to a more convenient, greener, process. Moreover, substrate coordination and activation at the metal center would obviate the need for an expensive phosphoric acid catalyst. To test our ideas, three complexes were synthesized: 1 and 2, which have orthoor meta-phenyl-bridged pyridinium (HE) and [Cp*Rh(NN)Cl] centers, respectively, and 3, which lacks an HE substituent, as a control (Figure 1). The

Sequential deoxyfluorination approach for the synthesis of protected α,β,γ-trifluoro-δ-amino acids.

Backbone-homologated amino acids have been synthesized, containing three vicinal fluorine atoms placed stereospecifically along the carbon chain. Different trifluoro stereoisomers are found to have contrasting conformations, consistent with known stereoelectronic effects associated with C-F bonds.

Synthesis and supramolecular studies of chiral boronated platinum(II) complexes: insights into the molecular recognition of carboranes by β-cyclodextrin.

The synthesis and characterisation of a novel isomeric family of closo-carborane-containing Pt(II) complexes ((R/S)-(1-4)⋅2 NO(3)) are reported. Related complexes (5⋅NO(3) and 6⋅NO(3)) that contain the 7,8-nido-carborane cluster were obtained from the selective deboronation of the 1,2-closo-carborane analogues. The corresponding water-soluble supramolecular 1:1 host-guest β-cyclodextrin (β-CD) adducts ((R/S)-(1-4)⋅β-CD⋅2 NO(3)) were also prepared and fully characterised. HR-ESI-MS experiments confirmed the presence of the host-guest adducts, and 2D-(1) H{(11)B} ROESY NMR studies showed that the boron clusters enter the β-CD from the side of the wider annulus. Isothermal titration calorimetry (ITC) experiments revealed enthalpically driven 1:1 and higher-order supramolecular interactions between β-CD and (R/S)-(1-4)⋅2 NO(3) in aqueous solution. A comparison of the predominate 1:1 binding mode established that the affinity of β-CD for the guest molecule is mainly influenced by the pyridyl ring substitution pattern and chirality of the host, whilst the nature of the closo-carborane isomer also plays some role, with the most favourable structural features for β-CD binding being the presence of the 4-pyridyl ring, 1,12-closo-carborane, and an S configuration. The results reported here represent the first comprehensive calorimetric study of the supramolecular interactions between closo-carborane compounds and β-CD, and it provides fascinating insights into the structural features influencing the thermodynamics of this phenomenon.