Related Amides Research Articles

Expression of Mycobacterium smegmatis pyrazinamidase in Mycobacterium tuberculosis confers hypersensitivity to pyrazinamide and related amides.

A pyrazinamidase (PZase)-deficient pncA mutant of Mycobacterium tuberculosis, constructed by allelic exchange, was used to investigate the effects of heterologous amidase gene expression on the susceptibility of this organism to pyrazinamide (PZA) and related amides. The mutant was highly resistant to PZA (MIC, >2,000 microg/ml), in accordance with the well-established role of pncA in the PZA susceptibility of M. tuberculosis (A. Scorpio and Y. Zhang, Nat. Med. 2:662-667, 1996). Integration of the pzaA gene encoding the major PZase/nicotinamidase from Mycobacterium smegmatis (H. I. M. Boshoff and V. Mizrahi, J. Bacteriol. 180:5809-5814, 1998) or the M. tuberculosis pncA gene into the pncA mutant complemented its PZase/nicotinamidase defect. In both pzaA- and pncA-complemented mutant strains, the PZase activity was detected exclusively in the cytoplasm, suggesting an intracellular localization for PzaA and PncA. The pzaA-complemented strain was hypersensitive to PZA (MIC, </=10 microg/ml) and nicotinamide (MIC, >/=20 microg/ml) and was also sensitive to benzamide (MIC, 20 microg/ml), unlike the wild-type and pncA-complemented mutant strains, which were highly resistant to this amide (MIC, >500 microg/ml). This finding was consistent with the observation that benzamide is hydrolyzed by PzaA but not by PncA. Overexpression of PzaA also conferred sensitivity to PZA, nicotinamide, and benzamide on M. smegmatis (MIC, 150 microg/ml in all cases) and rendered Escherichia coli hypersensitive for growth at low pH.

Insertion loop 256-268 in coagulation factor IX restricts enzymatic activity in the absence but not in the presence of factor VIII.

Insertions in surface loops bordering the substrate-binding groove have been shown to play a major role in the interaction of serine proteases with their cognate inhibitors and substrates. In the present study, we investigated the functional role of factor IX insertion loop 256-268, and in particular of residues Asn(264) and Lys(265) therein. To this end, the purified and activated mutants des-(N264,K265)-FIX and FIX-K265A were compared to normal factor IXa with regard to a number of functional properties. The catalytic efficiency of des-(N264,K265)-FIXa and FIXa-K265A toward the amide substrate CH(3)SO(2)-Leu-Gly-Arg-pNA was 2-3-fold increased relative to that of normal factor IXa. Comparison of the activities of normal and mutant factor IXa toward a series of closely related amide substrates indicates that mutation of residues Asn(264)-Lys(265) influences the interactions in the S2-binding site. The mutations in loop 256-268 also increased the susceptibility of factor IXa to antithrombin inhibition by approximately 3-fold. Factor X activation experiments in the absence of factor VIIIa revealed that the catalytic efficiency of des-(N264,K265)-FIXa and FIXa-K265A was about 20 times higher than that of normal factor IXa. In the presence of factor VIIIa, however, the activity toward factor X was similar to that of normal factor IXa. The reduced sensitivity of the factor IXa mutants to factor VIIIa was neither due to an increase in factor IXa-dependent inactivation of factor VIIIa, nor to a lower affinity for this cofactor. Overall, these data demonstrate that loop 256-268 restricts the activity of factor IXa toward both synthetic and natural substrates. Complex formation with factor VIIIa alleviates the inhibitory effect of this insertion loop on the activation of FX.

Desulfonylation of Amides using Tributyltin Hydride, Samarium Diiodide or Zinc/Titanium Tetrachloride. A Comparison of Methods

Deprotection of N-sulfonylated amides can be achieved by reaction with Bu 3SnH, SmI 2 or TiCl 4/Zn. All three methods gave good yields (typically >60%) when using N-benzoyl or related amides while the corresponding N-acetyl derivatives proved to be inert to deprotection under the same reaction conditions. The mechanistic implications of this are discussed.

Synthesis and monolayer behaviors of optically active 1,12- dimethylbenzo[ c]phenanthrene-5,8-diamides and the formation of chiral langmuir-blodgett films

We previously reported that an optically active cyclic amide consisting of a helical chiral 1,12-dimethylbenzo[ c]phenanthrene-5, 8-dicarboxylic acid forms a stable monolayer on the water surface, and that the monolayer can be transferred on a solid support giving optically active Langmuir-Blodgett (LB) films. In this study, several related amides were synthesized, and their monolayer behaviors were investigated with expectation to prepare optically active LB films possessing functional groups. The result indicates that the cyclic amide structure and cyclohexyl moiety are essential for the formation of stable monolayer on the water surface. N-Alkylation of the secondary amide does not seriously affect the formation of monolayer, and chiral LB films are obtained by N,N-bis(3-meroaptopropyl) derivative of the cyclic amide.

Hydrolysis of naptalam and structurally related amides: inhibition by dissolved metal ions and metal (hydr)oxide surfaces.

In metal ion-free solutions, the secondary amide naptalam hydrolyzes more rapidly as the pH is decreased; intramolecular nucleophilic attack by a carboxylate side group is very likely involved. Millimolar levels of dissolved Cu(II) and Zn(II) inhibit hydrolysis between pH 3.6 and pH 6.5. Metal ion-naptalam complex formation is important since addition of the competitive ligand citrate lessens the inhibitory effect. The metal (hydr)oxide surfaces Al(2)O(3) and FeOOH inhibit naptalam hydrolysis to a lesser degree; inhibition is proportional to the extent of naptalam adsorbed. Secondary amides (propanil, salicylanilide, and N-1-naphthylacetamide) and tertiary amides (N-methyl-N-1-naphthylacetamide, furalaxyl, and N, N-diethylsalicylamide) that lack carboxylate side groups do not hydrolyze within 45 days of reaction, even when millimolar Cu(II) concentrations are present. Tertiary amides possessing carboxylate side groups (N,N-diethyl-3,6-difluorophthalamic acid and N, N-dimethylsuccinamic acid) do hydrolyze but are insensitive to the presence or absence of Cu(II). The inhibitory effect is believed to occur via metal coordination of (1) the carbonyl group of naptalam, which induces deprotonation of the amide group and makes the substrate less reactive toward nucleophilic attack; (2) the free carboxylate group of naptalam, which blocks intramolecular nucleophilic attack; or (3) a combination of the two.

The molecular structure, conformation, potential to internal rotation and force field of 2,2-difluoroacetamide as studied by gas electron diffraction and quantum-chemical calculations

2,2-Difluoroacetamide (DFA) has been studied by electron diffraction (ED), ab initio Hartree–Fock (HF), Møller–Plesset (MP2) and density functional theory (DFT) calculations using a 6-311++G** basis set. The calculations give one conformation where one of the C–F bonds is almost orthogonal to the CCON skeleton plane and a planar NH 2 group except for MP2, which predicts a slightly pyramidal NH 2 group. The molecular force field has been determined, and the fundamental frequencies have been assigned and compared with the limited spectroscopic data available for this molecule. The refined structural parameters were determined using constrained ED, i.e., ab initio results are included as constraints in the analysis. The structural parameters are: r g(N–H 4)=1.051(4), r g(CO)=1.212(1), r g(C–N)=1.352(7), r g(C–C)=1.535(2), r g(C–H 7)=1.113(8), r g(C–F 8)=1.358(3), ∠OCN=126.5(5), ∠CCN=114.3(3), ∠CCF 8=109.9(2), ∠H 7CF 8=107.9(3) and ∠CNH 4=122.2(10). Bond distances are in Å and bond angles in degrees. Uncertainties are one standard deviation from least-squares refinement using a diagonal weight matrix and inclusion of the uncertainty in the electron wavelength. The structural parameters are compared with those of related amides. The barrier height at the syn conformation, V 0, and the minimum of the potential energy function, φ min, are determined to be 2.8(5) kJ mol −1 and 35(1)°, respectively, which are in good agreement with theoretical calculations. The barrier height at the anti conformation, V 180, was fixed to its calculated value of 20.3 kJ mol −1.

A specific and sensitive assay to quantify the herbicidal activity of chloroacetamides

Based on a recently discovered property of chloroacetamide herbicides—the inhibition of the incorporation of oleic acid into sporopollenin of Scenedesmus acutus—a rapid quantitative test was developed for chloroacetamide-type herbicidal activity. In this test, algal cells are incubated for 3 h with [14C]oleic acid, saponified and the lipids (including non-saponifiable ones) extracted and discarded. The radioactivity incorporated into the residual non-lipid fraction is determined, and inhibition of this incorporation is used as a marker of chloroacetamide-type activity. Twenty-two agrochemical compounds were screened in this assay, which was found to be very sensitive, a 50% inhibition being reached with submicromolar herbicide concentrations. It is specific to chloroacetamides and related amides, since all these herbicides tested were potent inhibitors, while other herbicides were not. Highest inhibition was shown by cafenstrole followed by butachlor, fluthiamid, metazachlor, alachlor, dimethenamid, metolachlor and mefenacet. For these herbicides (with the exception of butachlor) sensitivity in the test was positively correlated (r=0·984) with their phytotoxic effect on the alga. © 1998 SCI

The molecular structure, conformation, potential to internal rotation and force field of 2,2,2-trifluoroacetamide as studied by gas electron diffraction and quantum chemical calculations

2,2,2-Trifluoroacetamide (TFA) has been studied by electron diffraction (ED), ab initio Hartree-Fock (HF), density functional theory (DFT), and MP2 calculations. The calculations give one conformation with one of the CF bonds anti to the CO bond and a planar NH 2 group, except for MP2/6–311 + + G∗∗, which predicts a slightly pyramidale NH 2 group. A molecular force field has been determined, and the fundamental frequencies have tentatively been assigned. The refined structural parameters were determined using constrained ED, i.e. ab initio results are included as constraints in the analysis. The structural parameters are: r g (N−H 4) = 1.040(4), r g (CO) = 1.211(2), r g (C−N) = 1.362(4), r g = 1.562(1), r g (C−F 7) = 1.347(1), ∠ α OCN = 126.5(2), ∠ α CCN = 116.3(4), ∠ α CCF 7 = 111.9(1), and ∠ α CNH 4 = 118.5(11). Bond distances are in Å and bond angles in degrees. Uncertainties are one standard deviation from least squares refinement using a diagonal weight matrix and inclusion of the uncertainty in the electron wavelength. The structural parameters have been compared with related amides. The Fourier coefficients V 3 and V 6 in the potential to internal rotation of the CF 3 group, V(α) = 1/2∗V 3∗(1 − cos(3∗α)) + 1/2∗V 6∗(1 − cos(6∗α)) , are determined to be 2.7(4) and − 0.7(3) kJ/mol, respectively. The syn barrier is experimentally determined to be 2.6(4) kJ/mol, which is in good agreeent with theoretical calculations.

Supramolecular assemblies of tungsten complexes with unusual chelating groups

Metal complexes of ligands with η 1- O coordinated carbonyl moieties are well-known throughout the inorganic literature. However, metal complexes containing authentic acid chloride ligands have not previously been isolated. The synthesis and characterization of compounds with the formula W(X)Cl 3(OPh-2-COCl) ( 2) [X  O ( 2a), NC 6H 3-2,6-(CH 3) 2 ( 2b), and Ph 2C 2 ( 2c)] are reported. The crystal structures of 2a and 2c were solved, showing the interaction of the acid chloride carbonyl moiety with the tungsten center. Complex 2c adopts a channelled structure having six-fold symmetric voids in the solid state. As was anticipated, the coordinated acid chloride of 2a reacts readily with nucleophiles to produce the ester WOCl 3(OPh-2-COPr n ) ( 3) and the amide WOCl 3(OPh-2-CONHBu t ) ( 4a). A related amide complex WOCl 3(OPh-2-CONH 2) ( 4b), synthesized by the reaction of WOCl 4 with salicylamide, displays an infinite-chain structure supported by hydrogen bonding between the amide group and the oxo ligand of an adjacent tungsten complex. The η 1- O coordinated nitro compounds W(X)Cl 3(OPh-2-NO 2) ( 5) [X  O ( 5a), NC 6H 3-2,6-(CH 3) 2 ( 5b), and Ph 2C 2 ( 5c)] have also been isolated and the crystal structure of 5c is reported.

The molecular structure, conformation, potential to internal rotation and force field of 2,2,2-trichloroacetamide as studied by gas electron diffraction and quantum chemical calculations

2,2,2-Trichloroacetamide (TCA) has been studied by electron diffraction (ED) and ab initio Hartree-Fock (HF) calculations using several basis sets and density functional theory (DFT). The HF calculations give essentially a syn conformation while the DFT calculations predict an unsymmetrical conformation with one of the Cl atoms perpendicular to the amide skeleton. ED support the DFT predictions. A molecular force field has been determined, and the assignments of the fundamental frequencies have been discussed. Refined structural parameters were determined using constrained ED, i.e. ab initio results are included in the analysis, are: r g(NH) = 1.033(8), r g(CO) = 1.213(3), r g(CN) = 1.347(4), r g(CCl 7) = 1.761(2), ∠ α OCN = 127.7(6), ∠ α CCN = 114.1(9), ∠ α CCCl 7 = 109.5(1). Bond distances are in A and bond angles in degrees. Uncertainties are one standard deviation from least-squares refinement using a diagonal weight matrix, but corrected for uncertainties in the electron wave length. The structural parameters have been compared with related amides, and the most unusual feature is the central sp 2-sp 3 CC bond length which is determined to be as long as r g = 1.591(5) A ̊ . The Fourier coefficients V 3 and V 6 in the potential to internal rotation of the CCl 3 group, V(ϕ) = 1 2 × V 3(1 − cos(3ϕ)) + 1 2 × V 6(1 − cos(6ϕ)) , are determined to be −0.8(14) and −1.1(4) kJ mol −1, respectively.

Semiconductor Photocatalysis. Part 22. Visible-Light Induced Photoreduction of CO2 with CdS Nanocrystallites — Importance of the Morphology and Surface Structures Controlled through Solvation by N,N-Dimethylformamide

Abstract Carbon dioxide (CO2) is reduced to CO on hexagonal CdS nanocrystallites (mean diameter of 4 nm) prepared in N,N-dimethylformamide (DMF) under visible-light irradiation with a quantum yield of 0.098 at λ = 405 nm in the presence of TEA as an electron donor. Solvation of the surface of CdS nanocrystallites by DMF or a related amide molecules should control the crystalline growth and stabilize the favorable morphology with a size quantization-effect. The effect of Cd2+ or H2S on CO production and the emission behavior, and the effect of electron donors suggest an important role of the surface structures of CdS–DMF for photo-induced electron transfer to CO2. The scope and limitation of the photoreduction of CO2 with semiconductor nanoparticles are discussed.

Copper(II) complexes of optically active binucleating ligands, N,N′-bis[2-pyridylmethyl and 2-(2-pyridyl)ethyl]-(S)-malamide and related amides

N,N′-Bis(2-pyridylmethyl)-3-hydroxyglutaramide [abbreviated as H 3(pmg)], optically active N,N′-bis{2-pyridylmethyl and 2-(2-pyridyl)ethyl}-(S)-malamide [H 3(lpm) and H 3(lpe), respectively], and the optically inactive analogues [H 3(ppm) and H 3(pem)] gave dimeric copper(II) complexes [Cu 2XL]·nH 2O (L = 1pm, 1pe, pmm, pem, and pmg; X = an anionic, exo-bridging ligand such as chloride, hydroxide, acetate (OAc), pyrazolate (pz), and nitrite ions). These complexes were characterized by magnetic susceptibilities, and electronic, circular dichroism, and infrared spectra. The amides act as a trivalent anionic ligand coordinating through the pyridine- and deprotonated amido-nitrogen atoms and through the deprotonated, pendant alkoxooxygen atom bridging two copper ions. Many of the complexes were magnetically subnormal at room temperature, the magnetic interaction between the two copper ions depending upon both L and the exo-bridges, X. The antiferromagnetic interaction increased in the order of X, Cl < OAc < OH < NO 2 < pz. Temperature dependence of the magnetic susceptibilities of some of the 1pm complexes ensured the order. A diamagnetic nickel(II) complex, Ni 2(pz)(lpm) · 2H 2O and a heterometallic CuNi(pz)(lpm) · 2H 2O were also obtained. The binuclear structure of Cu 2(pz)(ppm) · 3H 2O was confirmed by X-ray analysis.

Epoxidation with polystyrene-supported phosphonotungstic complexes

Epoxidation of alkenes with hydrogen peroxide was performed with polystyrene-supported peroxotungstiic catalytic species. These peroxo species were complexed by several phosphorus(V) ligands such as phosphine oxides, phosphonic acids and their related amides grafted onto the polymeric matrices through sequential reactions. The efficiencies and the possibilities of repeated uses of these catalysts are related to the kind of the macroligand and its polymeric backbone.

Photochemical Evolution of Interstellar/Precometary Organic Material

AbstractInfrared observations, combined with realistic laboratory simulations, have revolutionized our understanding of interstellar ice and dust, the building blocks of comets. Since comets are thought to be a major source of the volatiles on the primative earth, their organic inventory is of central importance to questions concerning the origin of life. Ices in molecular clouds contain the very simple molecules H2O, CH3OH, CO, CO2, CH4, H2, and probably some NH3and H2CO, as well as more complex species including nitriles, ketones, and esters. The evidence for these, as well as carbonrich materials such as polycyclic aromatic hydrocarbons (PAHs), microdiamonds, and amorphous carbon is briefly reviewed. This is followed by a detailed summary of interstellar/precometary ice photochemical evolution based on laboratory studies of realistic polar ice analogs. Ultraviolet photolysis of these ices produces H2, H2CO, CO2, CO, CH4, HCO, and the moderately complex organic molecules: CH3CH2OH (ethanol), HC(= O)NH2(formamide), CH3C(= O)NH2(acetamide), R-CN (nitriles), and hexamethylenetetramine (HMT, C6H12N4), as well as more complex species including polyoxymethylene and related species (POMs), amides, and ketones. The ready formation of these organic species from simple starting mixtures, the ice chemistry that ensues when these ices are mildly warmed, plus the observation that the more complex refractory photoproducts show lipid-like behavior and readily self organize into droplets upon exposure to liquid water suggest that comets may have played an important role in the origin of life.

Rapid estimation of relative amide proton exchange rates of 15N-labelled proteins by a straightforward water selective NOESY-HSQC experiment

A straightforward heteronuclear pseudo-3D NOESY-HSQC pulse sequence using radiation damping to selectively invert magnetization at the water frequency was developed to estimate the amide proton exchange rates in 15N-labelled proteins. The peak intensities in the resultant 2D spectrum allow a direct classification of amide proton exchange rates according to short (ms), intermediate (ms to s) or long (≥ s) residence times. This method was successfully used for the analysis of amide proton exchange rates in the 15N-labelled FruR DNA-binding domain and pertinent information about its dynamics was obtained.

A radical approach to N-desulfonylation

The deprotection of N-sulfonylated amides can be achieved under neutral conditions by reaction with tributylin hydride. Good yields are obtained using N-benzoyl and related amides while the corresponding N-acetyl derivatives are inert under the same reaction conditions. The mechanistic implications of this are discussed.

Mono- and Bimetallic Bipyridyl Polyene Complexes Containing 17-Electron Molybdenum Mononitrosyl Centers: Electrochemical, Spectroscopic, and Magnetic Studies

The monometallic bipyridyl complexes [MoTp*(NO)X(L-L)] [Tp* = HB(3,5-Me2C3HN2)3; L-L = 3,3‘-bipyridine, 4,4‘-bipyridine, 1,2-bis(4-pyridyl)ethane and X = Cl; L-L = 4,4‘-NC5H4(CHCH)nH4C5N, n = 0, 1, 2, 3, 4 (all trans) and X = Cl, I] and their bimetallic counterparts [{(NO)MoTp*X}2(L-L)] have been synthesized, together with [MoTp*(NO)Cl{4-NC5H4CHCHC(Me)CHCH}]2. The single crystal X-ray structure of [{MoTp*(NO)Cl}2{4,4‘-NC5H4(CHCH)4H4C5N}] confirms that the polyene chain is in the all-trans configuration and exhibits normal bond length alternation with [rCC−rCC] = 0.092 A. The Mo−Mo distance is 20.764(3) A, and the Mo−N(pyridyl) bond distance of 2.196(6) A indicates a much lower degree of Mo−(N)ligand π bonding than that found in related amide complexes where Mo−N(amide) distances are typically some 0.3 A shorter. Cyclic voltammograms of the monometallic complexes contain a single one-electron reduction process, whereas those of the bimetallic complexes contain two one-electron processes. The separation bet...

Agrobacterium rhizogenes-mediated transformation of Echinacea purpurea

Echinacea purpurea seedlings were inoculated with several Agrobacterium rhizogenes strains in order to obtain hairy roots. Infection with A. rhizogenes strains LMG63 and LMG150 resulted in callus formation. Upon infection with strains ATCC 15834 and R1601 hairy roots were obtained. Opine detection confirmed transformation of E. purpurea. Comparative HPLC fingerprint analysis of the alkamides from natural plant source, control tissues, and transformed callus and roots indicated that transformed callus and hairy roots might be a promising source for continuous and standardized production of the dodeca-2E,4E,8Z,10E/Z-tetraenoic acid isobutylamide and related amides.

Lithium-bis(di-tert-butylfluorsilyl)phosphid-ein cyclisches Zwitterion

We present the synthesis and X-ray structure of lithiumbis(di-tert-buthylfluorosilyl)phosphide ( 3). The molecule possesses a unique dipolar cyclic structure without direct LiP contact. The SiP −Si bond angle is approximately 100°, similar to that of other lithiumfluorosilylphosphide (I–IV). The energy of 3, calculated by ab initio methods, explains the invariance of the angle, which allows a comparison with the related amides.

ChemInform Abstract: Interaction of Nitromethane with Esters and Amides of 2‐Oxo‐2H‐1‐benzopyran‐3‐carboxylic Acid.

AbstractThe oxobenzopyrancarboxylic acid esters (I) and the related amides (V) are cleaved upon reaction with nitromethane (II) and potassium fluoride (or cesium fluoride) in the alcohols (III) to form mixtures of the diastereomeric 2‐(o‐hydroxyphenyl)‐3‐nitropropylmalonates (IV) or the corresponding diastereomeric monoamides (VI) and (VII).