M. Teresa Duarte

Electrochemical and structural studies of nickel(II) complexes with N2O2 Schiff base ligands 2. Crystal and molecular structure of N,N′-l,2-ethane-1,2-diyl-bis(2- hydroxyacetophenonylideneiminate)nickel(II), N, N′-1,2-cis cyclohexane-1,2-diyl-bis(2-hydroxyacetophenonylideneiminate)- nickel(II) and N,N′-1,2-benzene-1,2-diyl-bis(3,5-dichlorosalicylideneiminate)nickel(II)

Reductive and oxidative chemistry of three complexes of formula [Ni(L)], where L represents a N2O2 Schiff base pseudomacrocyclic ligand based on salicylaldehyde derivatives and three different diamines, was studied in (CH3)2SO: N,N′-1,2-ethane-1,2-diyl-bis(2-hydroxyacetophenonylideneiminate)nickel(II) (1); N,N′-1,2-cis-cyclohexane-1,2-diyl-bis(2-hydroxyacetophenonylideneiminate)nickel(II) (2); N,N′-1,2-benzene-1,2-diyl-(bis(3,5-dichlorosalicylideneiminate)nickel(II) (3). Electrochemical behavior of the complexes was determined by cyclic voltametry, and EPR spectroscopy was used to characterize the one-electron reduced/oxidized species. Reduction of the complexes 1 and 2 yielded Ni(I) complexes with a dxy ground state (gz>gx, gy), but the reduction of 3 is ligand-centered as suggested from the pseudo-isotropic radicalar EPR signal of frozen electrolyzed solutions. Oxidation of all three complexes is metal-centered and the oxidized products are low spin hexacoordinate Ni(III) species with two solvent molecules coordinated axially, with a dz2 ground state (gx, gy>gz). The crystal structures of the three Ni(II) complexes were determined from single crystal X-ray diffraction data collected with the use of Mo Kα radiation. 1: space group C2/c with a = 25.963(3), b = 7.2973(4), c = 17.357(2) A, β = 107.085(5)°, Z = 8 (R = 0.061); 2: space group P21/a with a = 9.645(6), b = 19.149(16), c = 10.743(5) A, β = 94.66(2)°, Z = 4 (R = 0.085); 3: space group P21/n with a = 13.372(5), b = 8.785(2), c = 16.534(5) A, β = 101.60(3)°, Z = 4 (R = 0.054). Crystal packing of 1 and 3 involves the pairing of two centrosymmetrical related molecules in dimers, but that of 2 shows no systematic parallel orientation of any part of the molecules. X-ray structural data have provided a rationale for the E12 values obtained for the reduction and oxidation processes.

Mechanosynthesis of the Metallodrug Bismuth Subsalicylate from Bi2O3 and Structure of Bismuth Salicylate without Auxiliary Organic Ligands

Mechanochemical reactions are versatile for the synthesis of new pharmaceutical forms, particularly cocrystals, salts and, since very recently, coordination complexes. Mechanochemistry can be very efficient for the synthesis of metal–organic frameworks (MOFs) and magnesium-based pharmaceuticals directly from inexpensive and otherwise inert materials, such as metal oxides or carbonates. In addition to short reaction times and the lack of bulk solvents, oxide-based mechanosynthesis also has the advantage of generating water as the sole byproduct. We now demonstrate how ionand liquid-assisted grinding (ILAG), previously utilized for the mechanosynthesis of large-pore MOFs and zeolitic imidazolate frameworks 6] based on zinc, can be extended to the pharmaceutical chemistry of bismuth oxide. We demonstrate the rapid and efficient conversion of Bi2O3 into a variety of bismuth salicylate complexes, including the commercial active pharmaceutical ingredient (API) bismuth subsalicylate (1), marketed under the trade name Pepto-Bismol. The pharmaceutical value of bismuth complexes with salicylic acid (H2sal) has been established over a century ago and still remains an area of active research. At least three different forms of bismuth salicylate, which differ in the stoichiometric ratio of bismuth and H2sal, have been reported. These are the API bismuth subsalicylate BiO(Hsal), the disalicylate (2) with assigned formula Bi2O(Hsal)4, [8] and the trisalicylate (3) involving bismuth and salicylic acid in the 1:3 stoichiometric ratio. Until now, the structure for any of these materials has remained unknown. Models for 1 and its biological activity were initially devised by Thurston et al. who used auxiliary chelating ligands to trap discrete oligonuclear clusters of Bi and salicylate anions (Hsal ), and by Burford et al. who explored complexation of Bi with thiosalicylic acid. The potential of mechanochemistry to generate bismuth carboxylates was revealed by Andrews and co-workers, 12] who investigated combined mechanoand thermochemical routes involving carboxylic acids and triphenylbismuth. With H2sal this approach provides different organobismuth salicylates unless the ratio of Bi to acid is 1:3, in which case it leads to the tricarboxylate 3 (Figure 1a). Recrystallization of 3 from acetone yielded metal–organic clusters containing coordinated solvent that are currently the best models for the structure of 1 (Figure 1b). Unfortunately, this synthetic pathway is of limited use due to regulatory aspects of organobismuth precursor and the formation of aromatic hydrocarbon byproducts.

Axial coordination of NHC ligands on dirhodium(II) complexes: Generation of a new family of catalysts

An efficient new methodology for the arylation of aldehydes is disclosed which uses dirhodium(II) catalysts and N-heterocyclic carbene (NHC) ligands. Complexes of Rh 2(OAc) 4 with one and two NHCs attached on the axial positions were successfully isolated, fully characterized, and used as catalysts in the reaction. The saturated monocomplex ((NHC 5)Rh 2(OAc) 4) 31 was shown to be the most active catalyst and was particularly efficient in the arylation of alkyl aldehydes. DFT calculations support participation of complexes with one axial NHC in the reaction as the catalysts active species and indicate that hydrogen bonds involving dirhodium unit, reactants, and solvent (alcohol) play an important role on the reaction mechanism.

Vanadium Diaminebis(phenolate) Complexes: Syntheses, Structures, and Reactivity in Sulfoxidation Catalysis

Vanadium diaminebis(phenolate) complexes of the general formulas [LVCl(THF)] (L = Me(2)NCH(2)CH(R)N(CH(2)-2-O-3,5-C(6)H(2)(t)Bu(2))(2), where R = H, Me) and [LV(O)X] [X = Cl; R = H (2), Me (3), O(i)Pr (4), (mu-O)V(O)L (5)] are described. All compounds display octahedral geometry and trans-O(Ph) coordination. For compounds 2, 3, and 5, only one isomer, presenting the V=O ligand trans to the tripodal nitrogen, was formed, while for 4, two isomers were observed by NMR in solution. The UV-vis and circular dichroism spectra of 2 and 3 display very intense charge-transfer transition bands from the phenolate donors to the vanadium, which are in agreement with the (51)V low-field shifts observed. All vanadium(V) complexes were tested as thioanisole sulfoxidation catalysts, revealing very high selectivity when H(2)O(2) was used as the oxidant. However, no enantioselectivity was observed even when enantiopure 3 was used as the catalyst precursor. (1)H and (51)V NMR studies were conducted for the reactions of 2 with aqueous solutions of H(2)O(2) in methanol-d(4) and in acetonitrile-d(3); 2 reacts with the solvents, leading to [LV(O)OMe], by replacement of Cl by MeO in methanol, and to a new vanadium aminebis(phenolate) complex, where the dimethylamine fragment of the original ligand L was replaced by CH(3)CN. In either case, (51)V NMR spectra suggest the formation of peroxovanadium species upon the addition of a H(2)O(2) solution. The subsequent addition of thioanisole to the methanol-d(4) solution leads to regeneration of the original complex.

Condensed phase behaviour of ionic liquid–benzene mixtures: congruent melting of a [emim][NTf2]·C6H6 inclusion crystal

The solid-liquid phase diagram of the (1-ethyl-3-methylimidazolium bis{(trifluoromethyl) sulfonyl} amide + benzene) system was determined and allowed us to identify and characterize an equimolar inclusion compound, [emim][NTf2].C6H6, with a congruent melting temperature: this type of behaviour, reported here for the first time, together with the X-ray structure of the inclusion compound lays emphasis upon the interactions that are responsible for the existence of liquid clathrates at higher benzene concentrations.

Decavanadates: a building-block for supramolecular assemblies

Abstract A donor–acceptor intermolecular interaction survey was performed for compounds containing the [H n V 10 O 28 ] 6– n anion, based on a Cambridge Structural Database search and on X-ray data examples in recent literature. Our aim was to systematize the supramolecular motifs present in the solid-state structures in order to understand the key factors determining the crystal packing of decavanadates and to develop a base for a methodology to construct new arrays. We were able to find four different main motifs: monomers, dimers, 1D and 2D arrays that were systematically analysed. The supramolecular assemblies found seem to depend both in the degree and site of protonation of the decavanadates, as well as on the size and shape of solvent and cation molecules.

New tetradentate N,N,N,N-chelating α-diimine ligands and their corresponding zinc and nickel complexes: synthesis, characterisation and testing as olefin polymerisation catalysts

A series of zinc complexes of the general formula {[ZnCl(ArN=C(An)-C(An)=NAr)](+)}(2)[Zn(2)Cl(6)](2-) (where Ar = 2-(1-benzyl-1H-1,2,3-triazol-4-yl)phenyl 2a, 2-(1-(1-phenylethyl)-1H-1,2,3-triazol-4-yl)phenyl 2b, 2-(1-phenyl-1H-1,2,3-triazol-4-yl)phenyl 2c; An = acenaphthene backbone) were prepared by the condensation of acenaphthenequinone with the corresponding o-triazolyl-substituted anilines (2-(1-benzyl-1H-1,2,3-triazol-4-yl)aniline 1a, 2-(1-(1-phenylethyl)-1H-1,2,3-triazol-4-yl)aniline 1b, 2-(1-phenyl-1H-1,2,3-triazol-4-yl)aniline 1c) which were formed by the copper(I)-catalyzed Huisgen[3+2] dipolar cycloaddition between 2-ethynylaniline and the corresponding azides in high yields, using anhydrous ZnCl(2) as the metal template, in boiling glacial acetic acid. Zinc complexes of the type [ZnCl(ArN=C(An)-C(An)=NAr)](+)[ZnCl(3)(NCCH(3))](-) (4a-c) were synthesized by crystallisation of the corresponding complexes 2a-c in acetonitrile, at -20 °C. After removal of zinc dichloride from complexes 2a-c by the addition of potassium oxalate, in dichloromethane, the tetradentate N,N,N,N-chelating α-diimine ligands of the type ArN=C(An)-C(An)=NAr (5a-c) were obtained. The new ligand precursors and zinc complexes were characterised by elemental analysis, (1)H and (13)C{(1)H} NMR spectroscopy, two-dimensional NMR spectroscopy, and X-ray diffraction. Reaction of the ligand precursors 5a-c with [NiBr(2)(DME)], in dichloromethane, gave nickel complexes of the type [NiBr(2)(ArN=C(An)-C(An)=NAr)] (6a-c). The results of single crystal X-ray diffraction characterisation and magnetic susceptibility measurements demonstrated that nickel complexes 6a-c possess octahedral geometries around the nickel atoms with variable configurations, the Br atoms of which can be ionized when dissolved in methanol. In preliminary catalytic tests, complexes 6a-c revealed to be active as catalysts for the polymerisation of norbornene and styrene, when activated by cocatalyst MAO. The characterisation of the polymers by (1)H and (13)C{(1)H} NMR spectroscopy, gel permeation chromatography/size-exclusion chromatography (GPC/SEC) revealed that these polymers were formed by a coordination addition mechanism.

Polymorphic gabapentin: thermal behaviour, reactivity and interconversion of forms in solution and solid-state

The various crystal forms of the neuroleptic drug gabapentin have been investigated, and in some cases re-investigated, by a combination of differential scanning calorimetry, hot stage microscopy and variable temperature powder diffraction methods in order to establish the relative stability of both its anhydrous and hydrated forms. A series of steps involving slurrying, heating, de-hydration and reaction with vapours of HCl have been performed. In this latter case, it has been possible to show that the reaction with HCl vapour leads to the same product as that obtained in solution. In slurry experiments in the absence of water, the most stable form, Form II, is invariably obtained, whereas in water, the slurry leads to the conversion of all crystal forms to the hemihydrated Form I. The conditions for the solid-state formation of the gabapentin-lactam de-hydration product have been analysed. Co-crystal formation has also been attempted. In the course of one such experiment, 1 : 1 co-crystals of gabapentin-lactam and benzoic acid were obtained.

Drug-containing coordination and hydrogen bonding networks obtained mechanochemically

In this communication we describe the solid-state preparation and structural characterization of the coordination and hydrogen bonding networks formed by the antibiotic 4-aminosalicylic acid and the nootropic drug piracetam with silver and nickel cations, respectively; the silver complex formed via solid-state reaction is anhydrous, while from solution its hydrated phase is obtained.

N-salicylideneamino-acidate complexes of oxovanadium(IV)—II. Synthesis, characterization and deamination of an n-salicylideneglycylglycinato complex

Abstract A vanadium(IV) complex VO(sal-glygly)(H 2 O) n ( 1 )(sal-glygly  N-salicylideneglycylglycinate; n = 1.5−3.0) has been isolated from relatively concentrated solutions containing oxovanadium(IV), glycylglycine and salicylaldehyde, and characterized by elemental analysis, thermal (TG and DSC), magnetic and spectroscopic techniques. From similar but dilute solutions the decavanadate, (NH 4 ) 4 (Na) 2 [V 10 O 28 ]·10H 2 O ( 2 ) was isolated after ageing: its structure has been determined by X-ray diffraction analysis. The NH 4 + cations were formed by deamination of the glycylglycine present in solution.