N-Aryl Modification in γ-Lactam: Design and Synthesis of Novel Monocyclic γ-Lactam Derivatives as Inhibitor for Bacterial Propagation

In search of novel γ-lactam antibacterial agents as non-β-lactam mimics of some γ-lactam antibiotics, N-aryl modification in the γ-lactam ring has been made to synthesize compounds 4–8 in two to six steps. Compound 4 was synthesized using the intermolecular Michael addition of diethyl N-(6-coumarinyl)-2-aminomalonate and 3-aryl/(2-heteroaryl)acryloyl chloride followed by intramolecular amidification. Hydrolysis and stereoselective decarboxylation of 4 resulted in the formation of trans- γ-lactam carboxylic acids (5), which on side chain homologation followed by saponification of the intermediate γ-lactam monoester (7) afforded γ-lactam carboxylic derivatives 8. Moderate to good bacterial growth inhibition was observed for some of the synthesized compounds against E. coli and S. aureus.     

Thermal Studies of Copper(II) Squarate Complexes of Diamines in the Solid State

CuL₂C₄O₄ [L=ethane-1,2-diamine (en)], CuL₂C₄O₄⋅2H₂O [L=N-methylethane-1,2-diamine (meen), N-ethylethane-1,2-diamine (eten),N-propylethane-1,2-diamine (pren), N-methyl-N’-ethylethane- 1,2-diamine (meeten) andpropane-1,2-diamine (pn)], CuL₂C₄O₄⋅0.5H₂O [L=N,N’-dimethylethane- 1,2-diamine (dmeen)], CuL₂C₄O₄⋅4H₂O [L=propane-1,2-diamine (pn)]and CuL₂C₄O₄⋅H₂O[L=2-methylpropane-1,2-diamine (ibn)] have been synthesized by the addition of respective diamine to finely powdered CuC₄O₄⋅2H₂O and their thermal studies have been carried out in the solid state. Cu(en)₂C₄O₄ upon heating loses one molecule of diamine with shar pcolour change yielding Cu(en)C₄O₄ which upon further heating transforms to unidentified products. All aquated-bis-diamine species [CuL₂C₄O₄⋅2H₂O, CuL₂C₄O₄⋅0.5H₂O and CuL₂C₄O₄⋅H₂O] upon heating undergo deaquation–anation reaction in the solid state showing thermochromism and transform to CuL₂C⁴O₄, which revert on exposure to humid atmosphere (RH ∼90%). All the squarato bis-diamine species, CuL₂C₄O₄, on further heating transform to unidentified products through the formation of CuLC₄O₄ as intermediates. The mono diamine species, have been isolated pyrolytically in the solid state and can be stored in a desiccator as well as in open atmosphere. They are proposed to be polymeric. This revised version was published online in August 2006 with corrections to the Cover Date.     

Efficient and Simple Approaches Towards Direct Oxidative Esterification of Alcohols

The present article describes novel oxidative protocols for direct esterification of alcohols. The protocols involve successful demonstrations of both “cross” and “self” esterification of a wide variety of alcohols. The cross‐esterification proceeds under a simple transition‐metal‐free condition, containing catalytic amounts of TEMPO (2,2,6,6‐tetramethyl‐1‐piperidinyloxy)/TBAB (tetra‐n‐butylammonium bromide) in combination with oxone (potassium peroxo monosulfate) as the oxidant, whereas the self‐esterification is achieved through simple induction of Fe(OAc)₂/dipic (dipic=2,6‐pyridinedicarboxylic acid) as the active catalyst under an identical oxidizing environment.     

Tuning Phenols with Intra‐Molecular Bond Shifted HYdrogens (IM‐SHY) as diaCEST MRI Contrast Agents

The optimal exchange properties for chemical exchange saturation transfer (CEST) contrast agents on 3 T clinical scanners were characterized using continuous wave saturation transfer, and it was demonstrated that the exchangeable protons in phenols can be tuned to reach these criteria through proper ring substitution. Systematic modification allows the chemical shift of the exchangeable protons to be positioned between 4.8 to 12 ppm from water and enables adjustment of the proton exchange rate to maximize CEST contrast at these shifts. In particular, 44 hydrogen‐bonded phenols are investigated for their potential as CEST MRI contrast agents and the stereoelectronic effects on their CEST properties are summarized. Furthermore, a pair of compounds, 2,5‐dihydroxyterephthalic acid and 4,6‐dihydroxyisophthalic acid, were identified which produce the highest sensitivity through incorporating two exchangeable protons per ring.     

Hexa boron-dipyrromethene cyclotriphosphazenes: synthesis, crystal structure, and photophysical properties

We have synthesized four examples of a cyclotriphosphazene ring appended with six boron-dipyrromethene dyes N(3)P(3)(BODIPY)(6) by adopting two different methods. In method I, 1 equiv of N(3)P(3)Cl(6) was treated with 6 equiv of meso-(o- or m- or p-hydroxyphenyl)boron-dipyrromethene in tetrahydrofuran (THF) in the presence of cesium carbonate. This afforded N(3)P(3)(BODIPY)(6) in yields ranging from 80 to 90%. In method II, we first prepared hexakis(p-formylphenoxy)cyclotriphosphazene N(3)P(3)(CHO)(6) by treating 1 equiv of N(3)P(3)Cl(6) with 6 equiv of 4-hydroxybenzaldehyde in the presence of cesium carbonate in THF. In the second step, N(3)P(3)(CHO)(6) was condensed with excess of pyrrole in the presence of catalytic amount of trifluoroacetic acid (TFA) in CH(2)Cl(2) at room temperature and afforded hexakis(p-phenoxy dipyrromethane)cyclotriphosphazene. In the last step, the hexakis(p-phenoxy dipyrromethane)cyclotriphosphazene was first oxidized with 6 equiv of DDQ in CH(2)Cl(2) at room temperature for 1 h followed by neutralization with triethylamine and further reaction with excess BF(3)·Et(2)O afforded the target N(3)P(3)(BODIPY)(6) in 16% yield. The route II was used only for the synthesis of one target compound whereas the route I was used for the synthesis of all four target compounds. The four compounds were characterized by mass, NMR, absorption, electrochemical, and fluorescence techniques. The crystal structure solved for one of the compounds revealed that the P(3)N(3) ring is slightly puckered and the six substituents were not interacting with each other and attained pseudo-axial and pseudo-equatorial positions. The photophysical studies in five different solvents indicated that the compounds exhibit large Stokes' shifts unlike reference monomeric BODIPYs indicating that the compounds are promising for fluorescence bioassays. The quantum yields and lifetimes of compounds 1-4 depends on the type of BODIPY unit attached to the cyclotriphosphazene ring.     

Origin of product ions in the MS/MS spectra of peptides in a quadrupole ion trap

Stored waveform inverse Fourier transform and double resonance techniques have been used in conjunction with a quadrupole ion trap to study the dissociation patterns of peptide ions. These experiments provide insight into the origin of individual product ions in an MS/MS spectrum. Results show for a series of leucine enkephalin analogues with five amino acid residues that the b ₄ ion is the main product ion through which many other product ions arise. It was also observed that the percentage of the a ₄ product ions that are formed directly from the protonated molecule (M+H)⁺ depends on the nature of the fourth amino acid residue. In addition, it was determined that in the peptides studied here lower series b ions (e.g., b ₃ arise from direct dissociation of higher series b ions (e.g., b ₄ only about 50% of the time.     

Density functional study of O2 adsorption on (100) surface of γ‐uranium

Chemisorption of the oxygen molecule on the (100) surface of γ‐uranium was investigated using the generalized gradient approximation to Density Functional Theory. Dissociative adsorptions of O₂ are found to be significantly favored compared to molecular adsorptions. Interstitial adsorptions of molecular oxygen are less probable, as no bound states are found in this case. Only after dissociation of O₂ is atomic oxygen diffusion through the surface possible. The O 2p orbitals are found to hybridize with U 5f bands, and some of the U 5f electrons become more localized. A significant charge transfer from the first layer of the uranium surface to the oxygen atoms is found to occur, making the bonding partly ionic. For the most favored site, the dissociative chemisorption energy is ～9.5 eV, which indicates a strong reaction of uranium surface with oxygen. Spin polarization does not have a significant effect on the chemisorption process. For most of the sites and approaches, chemisorption configurations are almost same for both spin‐polarized and non‐spin‐polarized cases. For the most favored chemisorption sites of oxygen on uranium, paramagnetic adsorption is slightly stronger, by 0.304 eV, compared to magnetic adsorption. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2005     

Transition metal carbene chemistry. 4. Nucleophilic attachment of DABCO to fischer carbene complexes in MeCN

Rate constants for the attachment of DABCO (1,4-diazabicyclo[2.2.2]octane) to Fischer carbene complexes of the type (CO)(5)Cr=C(XR)C(6)H(4)Z (X = O and S) in dry MeCN at 25 degrees C are reported. Hammett rho values are 2.18 +/- 0.13 and 0.89 +/- 0.07 for DABCO reactions with (CO)(5)Cr=C(OMe)C(6)H(4)Z (10-Cr-Z) and (CO)(5)Cr=C(SMe)C(6)H(4)Z (11-Cr-Z), respectively. The rho values for the reaction of 10-Cr-Z and 11-Cr-Z with CH(CN)(2)(-) in 50% MeCN-50% H(2)O (v/v) are comparable to the present reactions. The reaction of DABCO with 10-Cr-Z is more closely related to the reaction of (n-Bu)(3)P with (CO)(5)W=C(OMe)C(6)H(5)-Z (23) which also provided a rho value 2.22. The much higher rho values and hence much higher reactivity of methoxy carbene complexes over the corresponding thiomethyl derivatives fit a pattern observed previously for alkoxide ion, OH(-), amine, and thiolate ion nucleophiles, and a rational explanation comes from the consideration of the substituent effects not only on the transition state but also on the reactant. A major difference between 10-Cr-Z and 11-Cr-Z is that the pi-donor effect of the methoxy group is much stronger than that of thiomethyl group. This leads to a substantial contribution of the zwitterionic form to the structure of 10-Cr-Z with much more localized positive charge on the methoxy group than the negative charge on the (CO)(5)Cr moiety. This leads to overall destabilization by an electron-withdrawing phenyl substituents resulting an increase in reactivity. The ethoxycarbene complexes are somewhat less reactive than their methoxy counterparts due to the somewhat more ground state stabilization through its stronger pi donor effect and partly due to steric crowding exerted by the slightly larger ethoxy group in the transition state. Higher k(1)(W)/k(1)(Cr) ratios for (thiomethyl)carbene complexes than methoxy or ethoxycarbene complexes are related to the intrinsic rate constant which is higher for ((thiomethyl)carbene)tungsten complexes than the corresponding Cr ones resulting in an enhanced ratio.     

Thermogravimetric analysis and hot-stage Raman spectroscopy of cubic indium hydroxide

The transition of cubic indium hydroxide to cubic indium oxide has been studied by thermogravimetric analysis complimented with hot-stage Raman spectroscopy. Thermal analysis shows the transition of In(OH)₃ to In₂O₃ occurs at 219 °C. The structure and morphology of In(OH)₃ synthesised using a soft chemical route at low temperatures was confirmed by X-ray diffraction and scanning electron microscopy. A topotactical relationship exists between the micro/nano-cubes of In(OH)₃ and In₂O₃. The Raman spectrum of In(OH)₃ is characterised by an intense sharp band at 309 cm⁻¹ attributed to ν₁ In–O symmetric stretching mode, bands at 1137 and 1155 cm⁻¹ attributed to In-OH δ deformation modes, bands at 3083, 3215, 3123 and 3262 cm⁻¹ assigned to the OH stretching vibrations. Upon thermal treatment of In(OH)₃, new Raman bands are observed at 125, 295, 488 and 615 cm⁻¹ attributed to In₂O₃. Changes in the structure of In(OH)₃ with thermal treatment is readily followed by hot-stage Raman spectroscopy.     

Synthesis and thermal analysis of indium-based hydrotalcites of formula Mg<Subscript>6</Subscript>In<Subscript>2</Subscript>(CO<Subscript>3</Subscript>)(OH)<Subscript>16</Subscript>·4H<Subscript>2</Subscript>O

Insight into the unique structure of layered double hydroxides (LDHs) has been obtained using a combination of X-ray diffraction and thermal analysis. Indium containing hydrotalcites of formula Mg₄In₂(CO₃)(OH)₁₂·4H₂O (2:1 In-LDH) through to Mg₈In₂(CO₃)(OH)₁₈·4H₂O (4:1 In-LDH) with variation in the Mg:In ratio have been successfully synthesised. The d(003) spacing varied from 7.83 Å for the 2:1 LDH to 8.15 Å for the 3:1 indium containing LDH. Distinct mass loss steps attributed to dehydration, dehydroxylation and decarbonation are observed for the indium containing hydrotalcite. Dehydration occurs over the temperature range ambient to 205 °C. Dehydroxylation takes place in a series of steps over the 238–277 °C temperature range. Decarbonation occurs between 763 and 795 °C. The dehydroxylation and decarbonation steps depend upon the Mg:In ratio. The formation of indium containing hydrotalcites and their thermal activation provides a method for the synthesis of indium oxide-based catalysts.