Suresh Gohil

Modification and cross-linking parameters in hyaluronic acid hydrogels—Definitions and analytical methods

Definitions and methods for the quantification of degree of modification and cross-linking in cross-linked hyaluronic acid (HA) hydrogels are outlined. A novel method is presented in which the HA hydrogel is degraded by the enzyme chondroitinase AC and the digest product analyzed by size exclusion chromatography combined with electrospray ionization mass spectrometry (SEC-ESI-MS). This method allows for the determination of effective cross-linker ratio (CrR) which together with the degree of modification (MoD), determined by, e.g. (1)H NMR spectroscopy, enables the calculation of the degree of substitution (DS) and degree of cross-linking (CrD). The method, could be applicable to the major cross-linked HA hydrogels currently on the market, and is exemplified here by application to two HA hydrogels. The definitions and methods presented are important contributions in attempts to find relationships between MoD, DS and CrD to mechanical properties as well as to biocompatibility of HA hydrogels.

Influence of heteroligands on the composition, structure and properties of homo- and heterometallic zirconium alkoxides. Decisive role of thermodynamic factors in their self-assembly

Interaction of the commercial “Zr(OnPr)4” with an excess of iPrOH provides in high yields a new solid crystalline but highly soluble precursor Zr2(μ-OnPr)2(OiPr)6(iPrOH)2 (2). Interaction of 1 eq. of 2 with 1 eq. of Co(acac)2 results in quantitative transformation into a mixture of Co2Zr2(OnPr)4(OiPr)6(acac)2 (3), with a structure representing a fragment of hexagonal packing of metal atoms and alkoxide ligands (typical for derivatives of primary alcohols), and Zr2(OiPr)6(acac)2 (4). Reaction of 1 eq. of homoleptic zirconium isopropoxide, Zr2(OiPr)8(iPrOH)2 (1), with 1 eq. of Co(acac)2 provides a new complex CoZr2(OiPr)8(acac)2 (5) having a linear chain structure (characteristic of sec-alcohol derivatives) in quantitative yield. Microhydrolysis of a mixture of 1.5 eq. of 2 and 1 eq. of Co(acac)2 gave in moderate yield CoZr3O(OnPr)3(OiPr)5(acac)4 (6), with a tetrahedral CoZr3O core characteristic of zirconium sec-oxoalkoxides. Modification of a solution of barium and zirconium isopropoxides in toluene (Ba∶Zr = 1∶1) with 1.5 eq. of Hacac results almost quantitatively in a mixture of insoluble Ba(acac)2 and soluble and volatile heterometallic alkoxide Ba2Zr4(OiPr)18(acac)2 (7). Addition of 2 eq. of Hthd to a mixture of barium and zirconium n-propoxides in toluene (Ba∶Zr = 1∶1) gives highly soluble and volatile complex Ba2Zr2(thd)4(OnPr)8(nPrOH)2 (8). Reaction of the in situ obtained Ba(thd)2 with 0.5 eq. of 2 provided almost quantitatively another highly soluble and volatile precursor Ba2Zr2(thd)4(OnPr)2(OiPr)6 (9). Addition of 2 eq. of Hthd to a mixture of strontium and zirconium isopropoxides in toluene (Sr∶Zr = 1∶1) gives highly soluble complex Sr2Zr2(thd)4(OiPr)8 (10) volatilized on heating via complete decomposition into Sr(thd)2, Zr(thd)2(OiPr)2 and non-volatile products. Bimetallic hydroxo-isopropoxides of strontium and barium, Sr2Zr2(OH)2(OiPr)10(iPrOH)4 (11) and Ba2Zr2(OH)2(OiPr)10(iPrOH)6 (12), have been obtained in good yields via microhydrolysis of solutions of isopropoxides in toluene/isopropanol media. All compounds have been characterized by a variety of spectroscopic techniques, and compounds 1–9 and 11–12 also by X-ray single crystal studies. The principles in construction of zirconium alkoxides – products of thermodynamically controlled molecular self-assembly – and their stability and reactivity are discussed in connection with the sterical role played by the chosen ligands.

An approach to heterometallic alkoxide-β-diketonate complexes with a M4O4 cubane-like core and new prospects of their application in preparation of solid catalysts. X-ray single crystal study of (Co,Ni)4(acac)4(μ3-OMe)4(MeOH)4, Co2Ni2(acac)4(μ3-OMe)4(OAc)2 and Mg4(acac)4(μ3-OMe)4(MeOH)4

Abstract The interaction of the individual M4(acac)4(μ3-OMe)4(MeOH)4 complexes, M=Co, Ni in toluene/methanol media provided crystals of (Co,Ni)4(acac)4(μ3-OMe)4(MeOH)4 (I) — the product of co-crystallization of isomorphous products. The oxidation of a MeOH solution of I in air in the presence of NaOAc and aminoalcohols as catalysts gave Co2Ni2(acac)4(μ3-OMe)4(OAc)2 (II), an individual heterometallic derivative. The interaction of Mg(OCH(CH3)CH2NMe2)2 with Cu(acac)2 in toluene/methanol media produced Mg4(acac)4(μ3-OMe)4(MeOH)4 (III) as the only isolatable product. The starting Co and Ni homometallic complexes as well as the heterometallic CoNi complex II were used to prepare the zeolite-supported oxide catalysts which exhibited extremely high activity towards methanol oxidation.

Synthesis, characterization and molecular structures of homo- and heterometallic nickel(II) aminoalkoxides Ni(η2-ORN)2 and Ni(Ni0.25Cu0.75)2(μ3-OH)(μ-OAc)(η1-OAc)2(μ,η2-ORN)2(η2-RNOH) (RN=CHMeCH2NMe2)

Abstract Soluble Ni(II) alkoxides, namely the dimethylaminoisopropoxide clathrate with toluene, Ni(η2-ORN)2·C7H8 (I) and the solvent free crystalline Ni(ORN)2 (RN=CHMeCH2NMe2) species (II), obtained by sublimation of I in vacuo, were characterized by X-ray diffraction. The reaction between Ni(ORN)2 and copper carboxylates such as propionate and copper acetate hydrate in hydrocarbons afforded [CuNi2(O2CEt)3(ORN)3(RNOH)] (III) and [Ni(Ni0.25Cu0.75)2(μ3-OH)(μ-OAc)(η1-OAc)2(μ,η2-ORN)2(η2-RNOH)] (IV), respectively. The structures of I and II are based on square planar molecules of the trans isomer. The structure of IV corresponds to triangular aggregates with a M3(μ3-OH) central core. The remarkable feature is the presence of three types of coordination sphere, one metal is coordinated octahedrally and corresponds to nickel and the other two have square pyramidal and square planar coordinations, respectively, and an electronic density corresponding to Cu (75%) and Ni (25%). The monodentate behavior of the two acetato ligands is stabilized by intramolecular hydrogen bonding involving the hydroxyl functionalities of the μ3-hydroxo (2.776(9) A) and the solvated aminoalcohol ligand (2.573(6) A). Magnetic data in the 20–300 K temperature range for III and IV account for three uncoupled metal centers at high temperature whereas ferromagnetic exchange interactions are likely below 20 K.

Identification of a sucrose diester of a substituted β-truxinic acid in oats

Abstract A novel compound, 4,4′-dihydroxy-3,3′-dimethoxy-β-truxinic acid esterified to sucrose through the fructosyl 3-and 6-carbons ( 1 ), was isolated from oat grains ( Avena sativa L.). Its structure was determined by a combination of mass spectrometry and 1-D and 2-D NMR. The amounts of 1 in groats of six different oat cultivars ranged from 101 to 150 μg g −1 (dry wt). None was detected in the hulls. The free diacid, 4,4′-dihydroxy-3,3′-dimethoxy-β-truxinic acid ( 2 ), could not be detected in groats nor in hulls.

Cyclopeptide alkaloids from Heisteria nitida

Abstract Integerrenine, and a new cyclopeptide alkaloid, containing the unusual amine oxide function, anorldianine 27-N oxide, stigmasterol, β-sitosterol, lupeol, (+)-catechin, (—)-epicatechin and 4-hydroxy-2-methoxy benzoic acid were isolated from the Ecuadorian medicinal plant Heisteria nitida (Engl.), Olacaceae. The structures were determined by UV, IR, NMR and mass spectroscopic investigations and chemical transformations. The cyclopeptide alkaloids have been isolated and characterized for the first time in the family Olacaceae.

Interaction of some divalent metal acetylacetonates with Al, Ti, Nb and Ta isopropoxides. Factors influencing the formation and stability of heterometallic alkoxide complexes

Interaction of Co(acac)2 with 2 eq. of Ti(OiPr)4 in hexane leads to an equimolar mixture of the new heterometallic complex [Co2Ti2(acac)2(OiPr)10] (1) and the known heteroleptic alkoxide Ti2(acac)2(OiPr)6. When redissolved in iPrOH 1 is destroyed, forming [Co2(acac)4(iPrOH)2] (2) as the only isolable crystalline product. Reaction of Co(acac)2 with 3 eq. of Ta(OiPr)5 gives [Co2Ta2(OiPr)14] (3) together with Ta(acac)(OiPr)4. Reaction of Ni(acac)2 with 4 eq. of Nb(OiPr)5 produces the heterometallic complex [NiNb2(OiPr)12] (4). Reactions of M(acac)2 (M = Co, Ni, Mg and Zn) with Al(OiPr)3 in 1 ∶ 2 ratios provides access to [MAl2(OiPr)4(acac)4] [M = Co (5), Ni (6), Mg (7)] and [Zn2Al2(OiPr)6(acac)4] (8) respectively. When redissolved in iPrOH, [NiAl2(OiPr)4(acac)4] (6) is destroyed, forming a mixture of [Ni2(acac)4(iPrOH)2] (9), Al(OiPr)3 and Al(acac)3. Interaction of M(acac)2, (M = Co, Ni) with metal isopropoxides in iPrOH as well as their recrystallization from iPrOH give 2 and 9 respectively. 5–7 are unstable in the hydrocarbon solution on heating, decomposing with formation of [M2Al2(OiPr)6(acac)4], along with Al(acac)3 and heterometallic alkoxide species. Mg(acac)2 was found to recrystallize unchanged from the solutions of Ti(OiPr)4 in toluene. The solution structure and stability of the heterometallic complexes has been investigated by UV-Vis spectroscopy and NMR, and the details of their decomposition on sublimation by mass-spectroscopy. The factors influencing the formation and stability of heterometallic complexes originating from the reactions of divalent metal acetylacetonates with metal isopropoxides are discussed.

Preparation of trimetallic alkoxide complexes exploiting the isomorphous substitution approach.: Synthesis, X-ray single crystal and mass-spectrometric study of NbTa(OMe)8(ReO4)2 and Nb2Ta2O2(OMe)14(ReO4)2

Abstract Alkoxylation of the rhenium heptoxide, Re2O7, with the bimetallic niobium-tantalum methoxide, NbTa(OMe)10, provided, dependent on the reaction conditions, either (Nb,Ta)2(OMe)8(ReO4)2 (I) or (Nb,Ta)4O2(OMe)14(ReO4)2 (II). Niobium and tantalum are distributed very uniformly between the correspondent positions in the molecular structure of I (only one symmetry independent position present for MV atoms). In the structure of II, the metal atom position connected to the perrhenate ligand has higher niobium content, while that connected to alkoxide groups and the oxoligand has higher tantalum content. Possible reasons for this difference and its influence on the decomposition behavior of I and II on vacuum sublimation are discussed.

Determination of substitution positions in hyaluronic acid hydrogels using NMR and MS based methods

In hydrogels of cross-linked polysaccharides, the total amount of cross-linker and the degree of cross-linking influence the properties of the hydrogel. The substitution position of the cross-linker on the polysaccharide is another parameter that can influence hydrogel properties; hence methods for detailed structural analysis of the substitution pattern are required. NMR and LC-MS methods were developed to determine the positions and amounts of substitution of 1,4-butanediol diglycidyl ether (BDDE) on hyaluronic acid (HA), and for the first time it is shown that BDDE can react with any of the four available hydroxyl groups of the HA disaccharide repeating unit. This was achieved by studying di-, tetra-, and hexasaccharides obtained from degradation of BDDE cross-linked HA hydrogel by chondroitinase. Furthermore, amount of linker substitution at each position was shown to be dependent on the size of the oligosaccharides. For the disaccharide, substitutions were predominantly at ΔGlcA-OH2 and GlcNAc-OH6 while in the tetra- and hexasaccharides, it was mainly at the reducing end GlcNAc-OH4. In the disaccharide there was no substitution at this position. Since chondroitinase is able to completely hydrolyse non-substituted HA into unsaturated disaccharides, these results indicate that the enzyme is prevented to cleave on the non-reducing side of an oligosaccharide substituted at the reducing end GlcNAc-OH4. The procedure can be adopted for the determination of substitution positions in other types of polymers.

Solution interaction of O-donor ligand metal complexes with thiocarbonyl compounds—a new general route to metal sulfide materials

Molybdenum and tungsten oxoalkoxides {[MO(OMe)4]; M = Mo, W} and rhenium heptaoxide (Re2O7) reacted at room temperature with thiocarbonyl compounds such as N,N-dimethylthioformamide (DMTF), producing the crystalline metal sulfides MoS2, WS3 and Re2S7, respectively. The reaction mechanism involves, as the first step, the coordination of DMTF to a metal via the sulfur donor atom, followed by the subsequent metathesis of the latter with the doubly bonded oxygen atom. The final product is, depending on reaction conditions, a colloidal metal sulfide or up to 0.1 mm large metal sulfide crystals. By carrying out the reaction within a mesoporous alumina matrix, supported metal sulfide catalysts were obtained in one step. These catalysts were tested for catalytic hydrodesulfurization and their activity compared with catalysts prepared by traditional methods. Reaction of nickel and zinc acetylacetonates and aminoalkoxides with DMTF in hydrocarbon media was found to provide colloids and, on aging, fine powder precipitates of NiS and ZnS.