Zinc(II) mediated synthesis of an N-substituted 2-(2-pyridyl)imidazole from a 1,2-diketone and 2-(aminomethyl)pyridine and its ligational behaviour

Reaction of anhydrous ZnCl2 with the 1:2 condensate (L) of benzil and 2-(aminomethyl)pyridine in methanol gives monomeric ZnL'Cl-2 (1) where L' is 2-[(4,5-diphenyl-2-pyridin-2-yl-1H-imidazol-1-yl)-methyl]pyridine. In the X-ray crystal structure, 1 is found to contain tetrahedral zinc with an N2Cl2 coordination sphere and the N-substituent methylpyridine fragment hanging as a free arm. A tentative mechanism is proposed for the zinc mediated conversion of L-->L'. Demetallation of 1 by the action of aqueous NaOH yields L' in the free state. When L' is reacted with Zn(ClO4)(2).6H(2)O in a 1:2 molar proportion, [Zn(L')(2)](n)(ClO4)(2n).(H2O)(n/2).(CH2Cl2)(n/2) (2) is obtained. The zinc atom in 2, as revealed by X-ray crystallography, has a trigonal bipyramidal N-5 coordination sphere. There are two independent ligands in the asymmetric unit of 2. One of them bonds only to one zinc atom in a bidentate mode with the N-substituent methylpyridine hanging free while the other ligand binds to two different zinc atoms in a tridentate fashion, employing the N-substituent methylpyridine nitrogen atom to form the polymeric one-dimensional chain cation.

Aldol reaction of butane-2,3-diacetal protected methyl glycerate

The addition of aldehydes to butane-2,3-diacetal has been investigated. The reaction was shown to be both regioselective and diastereoselective by 1H NMR spectroscopy. The configuration of the newly formed stereocenter was determined by Mosher’s ester analysis.

Hydrogen bonded supramolecular elastomers : correlating hydrogen bonding strength with morphology and rheology

A series of six low molecular weight elastomers with hydrogen bonding end-groups have been designed, synthesised and studied. The poly(urethane) based elastomers all contained essentially the same hard block content (ca. 11%) and differ only in the nature of their end-groups. Solution state 1H NMR spectroscopic analysis of model compounds featuring the end-groups demonstrate that they all exhibit very low binding constants, in the range 1.4 to 45.0 M-1 in CDCl3, yet the corresponding elastomers each possess a markedly different nanoscale morphology and rheology in the bulk. We are able to correlate small variations of the binding constant of the end-groups with dramatic changes in the bulk properties of the elastomers. These results provide an important insight into the way in which weak non-covalent interactions can be utilized to afford a range of self-assembled polyurethane based materials that feature different morphologies.

Induced-fit binding of π-electron donor substrates to macrocyclic aromatic ether-imide-sulfones: a versatile approach to molecular assembly

Novel macrocyclic receptors which bind electron-donor aromatic substrates via π-stacking donor- acceptor interactions are obtained by cyclo-imidization of an amine-functionalized arylether-sulfone with pyromellitic- and 1,4,5,8-naphthalene-tetracarboxylic dianhydrides. These macrocycles complex with a wide variety of π-donor substrates including tetrathiafulvalene, naphthalene, anthracene, pyrene, perylene, and functional derivatives of these polycyclic hydrocarbons. The resulting supramolecular assemblies range from simple 1:1 complexes, to [2]- and [3]-pseudorotaxanes, and even (as a result of crystallographic disorder) an apparent polyrotaxane. Direct, five-component self-assembly of a metal-centred [3]pseudorotaxane is also observed, on complexation of a macrocyclic ether-imide with 8-hydroxyquinoline in the presence of palladium(II) ions. Binding studies in solution were carried out by 1H NMR and UV-visible spectroscopy, and the stoichiometries of binding were confirmed by Job plots based on charge-transfer absorption bands. The highest association constants are found for strong π-donor guests with large surface-areas, notably perylene and 1-hydroxypyrene, for which Ka values of 1.4 x 103 and 2.3 x 103 M-1 respectively are found. Single crystal X-ray analyses of the receptors and their derived complexes reveal large, induced-fit distortions of the macrocyclic frameworks as a result of complexation. These structures provide compelling evidence for the existence of strong, attractive forces between the electronically-complementary aromatic π-systems of host and guest.

Electronic properties, redox behavior, and interactions with H2O2 of pH-sensitive hydroxyphenyl-1,2,4-triazole-based oxovanadium(V)complexes

The syntheses and spectroscopic characterization of two 1,2,4-triazole-based oxovanadium(V) complexes are reported: 1(-)[VO(2)L1](-) and 2 [(VOL2)(2)(OMe)(2)] (where H(2)L1 = 3-(2'-hydroxyphenyl)-5-(pyridin-2"-yl)-H-1-1,2,4-triazole, H3L2 = bis-3,5-(2'-hydroxyphenyl)-1H-1,2,4-triazole). The ligand environment (N,N,O vs O,N,O) is found to have a profound influence on the properties and reactivity of the complexes formed. The presence of the triazolato ligand allows for pH tuning of the spectroscopic and electrochemical properties, as well as the interaction and stability of the complexes in the presence of hydrogen peroxide. The vanadium(IV) oxidation states were generated electrochemically and characterized by UV-vis and EPR spectroscopies, For 2, under acidic conditions, rapid exchange of the methoxide ligands with solvent [in particular, in the vanadium(IV) redox state] was observed.

Rifaximin modulates the colonic microbiota of patients with Crohn's disease: an in vitro approach using a continuous culture colonic model system.

Rifaximin, a rifamycin derivative, has been reported to induce clinical remission of active Crohn's disease (CD), a chronic inflammatory bowel disorder. In order to understand how rifaximin affects the colonic microbiota and its metabolism, an in vitro human colonic model system was used in this study. We investigated the impact of the administration of 1800 mg/day of rifaximin on the faecal microbiota of four patients affected by colonic active CD [Crohn's disease activity index (CDAI > 200)] using a continuous culture colonic model system. We studied the effect of rifaximin on the human gut microbiota using fluorescence in situ hybridization, quantitative PCR and PCR–denaturing gradient gel electrophoresis. Furthermore, we investigated the effect of the antibiotic on microbial metabolic profiles, using 1H-NMR and solid phase microextraction coupled with gas chromatography/mass spectrometry, and its potential genotoxicity and cytotoxicity, using Comet and growth curve assays. Rifaximin did not affect the overall composition of the gut microbiota, whereas it caused an increase in concentration of Bifidobacterium, Atopobium and Faecalibacterium prausnitzii. A shift in microbial metabolism was observed, as shown by increases in short-chain fatty acids, propanol, decanol, nonanone and aromatic organic compounds, and decreases in ethanol, methanol and glutamate. No genotoxicity or cytotoxicity was attributed to rifaximin, and conversely rifaximin was shown to have a chemopreventive role by protecting against hydrogen peroxide-induced DNA damage. We demonstrated that rifaximin, while not altering the overall structure of the human colonic microbiota, increased bifidobacteria and led to variation of metabolic profiles associated with potential beneficial effects on the host.

The power of NMR. Part 1: the beginnings

Nuclear mnagnetic resonance (NMR) spectroscopy involves the excitation of nuclei by electromagnetic radiation in the radio-frequency range of the electromagnetic spectrum. For a nucleus to absorb energy from radiowaves in this way, it must hve the quantum mechanical property of spin. A spinning nucleus, such as that of the hydrogen atom, will dopt one f only two possible states when placed in a magnetic field. (In NMR, the hydrogen nucleus is often referred to as a proton, and is given the abbreviation 1H.) Az the strength of the magnetic field is increased, there is a proportional increase in the energy 'gap' between these two states. We can predic the resonant frequency at which any spinning nucleus will absorb energy from radio-frequency radiation as it jumps from the lower energy state to the upper state.

The power of NMR.: in two and three dimensions

Soon after its discovery in the 1950s, NMR had become an indispensable tool fr chemists. In the 1970s and 1980s, the power of the technique was extended from one dimension to two and even three dimensions, opening up exciting applkications in both chemistry and biochemistry. the success of one dimensional. high-resolution NMR stems from the unique insights that it can provide about molecular structure. The chemical shift of a nucleus gives invaluable information abut the chemical environment in which that nucleus is located, Coupling interactions between hydorgen nuclei, as revealed by characteristic splitting patterns inthe 1H-NMR spectrum, provide informaton about the loaction of one group of hydorgen atoms relative to others inthe molecule. And the nuclearf Overhauser effect (nOe) can shed light on molecular stereochemistry.

Synthesis and structural studies of a bis(carbamoyl methyl) sulfoxide complex of uranyl nitrate

A new tri-functional ligand iBu2NCOCH2SOCH2CONiBu2 was prepared and characterized. The coordination chemistry of this ligand with uranyl nitrate was studied with IR, 1H NMR, electrospray mass-spectrometry, thermogravimetry, and elemental analysis. The structure of [UO2(NO3)2(iBu2NCOCH2SOCH2CONiBu2)] was determined by single-crystal X-ray diffraction. The uranium(VI) ion is surrounded by eight oxygens in a hexagonal bipyramidal geometry. Four oxygens from two nitrates and two oxygens from the ligand form a planar hexagon. The ligand is a bidentate chelate, bonding through sulfoxo and one of the carbamoyl groups to uranyl nitrate.

Polyunsaturated fatty acids of the n-6 and n-3 series: effects on postprandial lipid and apolipoprotein levels in healthy men

OBJECTIVE: The present study was carried out to determine effects of test meals of different fatty acid compositions on postprandial lipoprotein and apolipoprotein metabolism. DESIGN: The study was a randomized, single blind design. SETTING: The study was carried out in the Clinical Investigation Unit of the Royal Surrey County Hospital. SUBJECTS: Twelve male normal subjects with an average age of 22.4 +/- 1.4 years (mean +/- SD) were selected from the student population of the University of Surrey; one subject dropped out of the study because he found the test meal unpalatable. INTERVENTIONS: The subjects were given three evening test meals on three separate occasions, in which the oils used were either a mixed oil (rich in saturated fatty acids and approximated the fatty acid intake of the current UK diet), corn oil (rich in n-6 fatty acids), or fish oil (rich in n-3 fatty acids) 40 g of the oil under investigation were incorporated into a rice-based test meal. Triacylglycerol-rich lipoproteins-triacylglycerol (TRL-TAG), TRL-cholesterol (TRL-cholesterol), plasma-TAG, plasma cholesterol (T-C), and serum apolipoprotein A-I and B (apo A-I and B) responses were measured. Postprandial responses were followed for 11 h. RESULTS: Postprandial plasma-TAG responses, calculated as incremental areas under the response curves (IAUC) were significantly reduced following the fish oil meal [365.5 +/- 145.4 mmol/l x min (mean +/- SD)[ compared with the mixed oil meal (552.0 +/- 141.7 mmol/l x min) (P < 0.05) and there was a strong trend towards the same direction in the TRL-TAG responses. In all instances, plasma-and TRL-TAG showed a biphasic response with increased concentrations occurring at 1h and between 3 and 7h postprandially. TRL-cholesterol, T-C, and serum apo A-I and B responses to the three meals were similar. CONCLUSIONS: The findings support the view that fish oils decrease postprandial lipaemia and this may be an important aspect of their beneficial effects in reducing risk of coronary heart disease (CHD). Further work is required to determine the mechanisms responsible for this effect.

A dialkylborenium ion via reaction of N-heterocyclic carbene–organoboranes with Brønsted acids—synthesis and DOSY NMR studies

A dialkylborenium ion stabilized by an N-heterocyclic carbene has been prepared for the first time by reaction of IMes-9-BBN-H with triflic acid. The ion-separated nature of the borenium ion was confirmed by 1H and 19F diffusion ordered NMR spectroscopy.

Nickel(II) and copper(II) complexes of Schiff base ligands containing N4O2 and N4S2 donors with pyrrole terminal binding groups: synthesis, characterization, X-ray structures, DFT and electrochemical studies

A series of hexadentate ligands, H2Lm (m = 1−4), [1H-pyrrol-2-ylmethylene]{2-[2-(2-{[1H-pyrrol-2-ylmethylene]amino}phenoxy)ethoxy]phenyl}amine (H2L1), [1H-pyrrol-2-ylmethylene]{2-[4-(2-{[1H-pyrrol-2-ylmethylene]amino}phenoxy)butoxy]phenyl}amine (H2L2), [1H-pyrrol-2-ylmethylene][2-({2-[(2-{[1H-pyrrol-2-ylmethylene]amino}phenyl)thio]ethyl}thio)phenyl]amine (H2L3) and [1H-pyrrol-2-ylmethylene][2-({4-[(2-{[1H-pyrrol-2-lmethylene]amino}phenyl)thio]butyl}thio) phenyl]amine (H2L4) were prepared by condensation reaction of pyrrol-2-carboxaldehyde with {2-[2-(2-aminophenoxy)ethoxy]phenyl}amine, {2-[4-(2-aminophenoxy)butoxy]phenyl}amine, [2-({2-[(2-aminophenyl)thio]ethyl}thio)phenyl]amine and [2-({4-[(2-aminophenyl)thio]butyl}thio)phenyl]amine respectively. Reaction of these ligands with nickel(II) and copper(II) acetate gave complexes of the form MLm (m = 1−4), and the synthesized ligands and their complexes have been characterized by a variety of physico-chemical techniques. The solid and solution states investigations show that the complexes are neutral. The molecular structures of NiL3 and CuL2, which have been determined by single crystal X-ray diffraction, indicate that the NiL3 complex has a distorted octahedral coordination environment around the metal while the CuL2 complex has a seesaw coordination geometry. DFT calculations were used to analyse the electronic structure and simulation of the electronic absorption spectrum of the CuL2 complex using TDDFT gives results that are consistent with the measured spectroscopic behavior of the complex. Cyclic voltammetry indicates that all copper complexes are electrochemically inactive but the nickel complexes with softer thioethers are more easily oxidized than their oxygen analogs.

Fulvalene cyclopentadienyl titanium and zirconium(III) and -(IV) complexes. X-Ray crystal structure of [{Ti(η5-C5H5) Cl}2 (μ-O)(μ-η5-η5-C10H8)]

The reaction of the fulvalene titanium(III) hydride [{Ti(η5-C5H5)(μ-H)}2(μ-η5-η5-C10H8)] (1) with chlorine leads to [{Ti(η5-C5H5)(μ-Cl)}2(μ-η5-η5-C10H8)] (3) and [{Ti(η5-C5H5)Cl2}2(μ-η5-η5-C10H8)] (4). The reaction of 3 with azobenzene, in wet toluene, gives [{Ti(η5-C5H5)Cl}2(μ-O)(μ-η5-η5-C10H8)] (5) and 1,2-diphenyl hydrazine. The alkylation of 4 and the analogous zirconium complex [{Zr(η5-C5H55)Cl2}2(μ-η5-η5-C10H8)] (2) with LiCH2SiMe3 or LiCH3 permits isolation of the tetraalkyl derivatives [{M(η5-C5H5)(CH2SiMe3)2}2(μ-η5-η5-C10H8)] (M  Ti (6); Zr (8)) and [{Ti(η5-C5H5)(CH3)2}2(μ-η5-η5C10H8)] (7). All the new fulvalene compounds were characterized by IR, and 1H and 13C NMR spectroscope, and mass spectra and 5 by X-ray diffraction. The structure of 5 is very similar to that of the comparable TiIV compound [{Ti(η5-C5H5)2Cl}2(μ-O)] except for the smaller TiOTi angle (159.4° against 173.81°) and a significant deviation from linearity.

A hydrogen-1 nuclear magnetic resonance, mass spectral and extended Hückel study of some olefin complexes of rhodium(I) and iridium(I) and the crystal and molecular structure of η4-2,4-dimethylpenta-1,4-diene(η5-formylcyclopentadienyl)rhodium(I)

A 1H NMR study of monosubstituted η-cyclopentadienyl-rhodium(I) complexes of type LLRh(C5H4X) and -iridium(I) complexes of type L2Ir(C5H4X) (L = ethene, LL = 1,3- or 1,5-diolefin; X = C(C6H5)3, CHO, or COOCH3) has been carried out. For complexes of both metals in which the neutral ligand is ethene or a non-conjugated diolefin the NMR spectra of the cyclopentadienyl protons are unusual in that H(2), H(5) resonate to high field either at room temperature or below. The corresponding NMR spectra for the cyclopentadienyl ring protons of complexes where the neutral ligand is a conjugated diene are, with one exception, normal. A single crystal X-ray structural analysis of (η4-2,4-dimethylpenta-1,4-diene)(η5-formylcyclopentadienyl)rhodium(I) (which exhibits an abnormal 1H NMR spectrum) reveals substantial localisation of electron density in the C(3)C(4) Cp ring bond (1.283(33) Å) which may be consistent with a contribution from an ‘allyl-ene’ rotamer to the ring—metal bonding scheme. An extended Hückel calculation with self consistent charge iteration was performed on this complex. The results predict a greater Mulliken overlap population for the C(3)C(4) bond in the cyclopentadienyl ring and show that the localisation is dependent on both the Cp ring substituent and the nature of the diolefin. The mass spectral fragmentation patterns of some representative diene complexes of iridium(I) and rhodium(I) are presented.

Anticancer activity of organotin compounds. 2. Interaction of diorganotin dihalides with nucleic acid bases and nucleosides; the synthesis of adenine, adenosine and 9-methyladenine adducts

The syntheses of the complexes formulated as SnMe2Cl2(Ad)2 (I), SnMe2Cl2(Ado)2 (II), SnMe2Cl2- (9-MeAd)2 (III) [Ad = adenine, Ado = adenosine, 9-MeAd = 9-methyladenine] as well as the more unexpected SnPhCl2(OH)(Ad)2·3H2O (IV) and SnPhCl3(Ado)2 (V) by reaction of SnMe2Cl2 or SnPh2Cl2 with the appropriate bases in methanol is described. 1H NMR studies suggest that coordination is through the N-7 position of the adenine base.