Amide NH Research Articles

DRIFTS Study of Ammonia Activation over CaO and Sulfated CaO for NO Reduction by NH3

CaO catalyzes NH(3) oxidation, while sulfated CaO catalyzes NO reduction by NH(3) in the presence of O(2), and the adsorption and transformation of ammonia over CaO and sulfated CaO has been investigated by in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) to understand their catalytic mechanism. It has been found that ammonia is first adsorbed over Lewis or Brönsted acid sites, and later undergoes hydrogen abstraction giving rise to either NH(2) amide or NH imide intermediates. The intermediates react with NO or lattice O to produce N(2) or NO. Comparing the DRIFTS of NH(3) adsorption over CaO and sulfated CaO, it is obvious that ammonia adsorbed over CaO is activated mainly in NH form apt to react with surface oxygen to produce NO, while ammonia adsorbed over sulfated CaO is activated mainly in NH(2) form apt to reduce NO. The DRIFTS results agree with experimental data and explain the catalytic mechanisms of CaO and sulfated CaO.

Hydrogen-bonding interactions in ferrocene-peptide conjugates containing valine

The synthesis and characterization of a series of ferrocene (Fc) peptide conjugates containing the amino acid valine is reported, where the peptide substituents are part of the hydrophobic sequence of the amyloid β-peptide. The hydrogen-bonding (H-bonding) interaction in these compounds is studied by variable temperature 1H NMR spectroscopy. The solid-state structures, determined by single crystal X-ray crystallography, of two of the conjugates (Fc[CO-Leu-Val-OMe] 2 1 and Fc[CO-Gly-Val-OH] 2 6) are reported. Both structures are stabilized by intramolecular H-bonds exhibiting the familiar “Herrick motif” involving the proximal amide NH and the amide CO of the adjacent amino acid. This motif is sufficiently rigid and is maintained in solution as suggested by CD studies. However, the intermolecular H-bonding patterns observed on conjugates 1 and 6 are significantly different resulting in very different supramolecular architectures. For conjugate 1, a more conventional set of head-to-tail stacking interactions which is stabilized by β-sheet-like H-bonding interactions between the individual molecules is observed. However, for conjugate 6, the presence of the C-terminal acid group and presumably the flexibility of the Gly linker enables the formation of a more open structure that contains hydrophobic channels occupied by solvent molecules.

Theoretical studies on sulfanilamide and derivatives with antibacterial activity: conformational and electronic analysis

Quantum chemical methods have been used to study the conformational and electronic properties of sulfanilamide and derivatives with antibacterial activity. Calculations at B3LYP/6-311++G(3df,2p) level of theory predict the existence of four conformers for sulfanilamide depending on the orientation of p-amino and amide groups. Focusing on the sulfonamide moiety, amide NH(2) and SO(2) groups could exist either in an eclipsed or staggered arrangement. Gas-phase results predict the eclipsed conformer to be most stable but opposite to what has been rationalized previously, no stabilizing hydrogen bonds between those groups has been found through NBO analysis. When solvent effect is taken into account through the IEF-PCM method, staggered conformer is preferred; in fact, eclipsed conformation changed when explicit solvent molecules were included. Conformational analysis of all derivatives has shown two global minima which are specular images. Five out of the seven derivatives studied adopted a particular minimum energy conformation with very similar geometries.

X-ray Crystal Structures of Monomeric and Dimeric Peptide Inhibitors in Complex with the Human Neonatal Fc Receptor, FcRn

The neonatal Fc receptor, FcRn, is responsible for the long half-life of IgG molecules in vivo and is a potential therapeutic target for the treatment of autoimmune diseases. A family of peptides comprising the consensus motif GHFGGXY, where X is preferably a hydrophobic amino acid, was shown previously to inhibit the human IgG:human FcRn protein-protein interaction (Mezo, A. R., McDonnell, K. A., Tan Hehir, C. A., Low, S. C., Palombella, V. J., Stattel, J. M., Kamphaus, G. D., Fraley, C., Zhang, Y., Dumont, J. A., and Bitonti, A. J. (2008) Proc. Natl. Acad. Sci. U.S.A., 105, 2337-2342). Herein, the x-ray crystal structure of a representative monomeric peptide in complex with human FcRn was solved to 2.6 A resolution. The structure shows that the peptide binds to human FcRn at the same general binding site as does the Fc domain of IgG. The data correlate well with structure-activity relationship data relating to how the peptide family binds to human FcRn. In addition, the x-ray crystal structure of a representative dimeric peptide in complex with human FcRn shows how the bivalent ligand can bridge two FcRn molecules, which may be relevant to the mechanism by which the dimeric peptides inhibit FcRn and increase IgG catabolism in vivo. Modeling of the peptide:FcRn structure as compared with available structural data on Fc and FcRn suggest that the His-6 and Phe-7 (peptide) partially mimic the interaction of His-310 and Ile-253 (Fc) in binding to FcRn, but using a different backbone topology.

Discovery of 4-(5-(Cyclopropylcarbamoyl)-2-methylphenylamino)-5-methyl-N-propylpyrrolo[1,2-f][1,2,4]triazine-6-carboxamide (BMS-582949), a Clinical p38α MAP Kinase Inhibitor for the Treatment of Inflammatory Diseases

The discovery and characterization of 7k (BMS-582949), a highly selective p38α MAP kinase inhibitor that is currently in phase II clinical trials for the treatment of rheumatoid arthritis, is described. A key to the discovery was the rational substitution of N-cyclopropyl for N-methoxy in 1a, a previously reported clinical candidate p38α inhibitor. Unlike alkyl and other cycloalkyls, the sp(2) character of the cyclopropyl group can confer improved H-bonding characteristics to the directly substituted amide NH. Inhibitor 7k is slightly less active than 1a in the p38α enzymatic assay but displays a superior pharmacokinetic profile and, as such, was more effective in both the acute murine model of inflammation and pseudoestablished rat AA model. The binding mode of 7k with p38α was confirmed by X-ray crystallographic analysis.

Bistable or Oscillating State Depending on Station and Temperature in Three‐Station Glycorotaxane Molecular Machines

High-yield, straightforward synthesis of two- and three-station [2]rotaxane molecular machines based on an anilinium, a triazolium, and a mono- or disubstituted pyridinium amide station is reported. In the case of the pH-sensitive two-station molecular machines, large-amplitude movement of the macrocycle occurred. However, the presence of an intermediate third station led, after deprotonation of the anilinium station, and depending on the substitution of the pyridinium amide, either to exclusive localization of the macrocycle around the triazolium station or to oscillatory shuttling of the macrocycle between the triazolium and monosubstituted pyridinium amide station. Variable-temperature (1)H NMR investigation of the oscillating system was performed in CD(2)Cl(2). The exchange between the two stations proved to be fast on the NMR timescale for all considered temperatures (298-193 K). Interestingly, decreasing the temperature displaced the equilibrium between the two translational isomers until a unique location of the macrocycle around the monosubstituted pyridinium amide station was reached. Thermodynamic constants K were evaluated at each temperature: the thermodynamic parameters DeltaH and DeltaS were extracted from a Van't Hoff plot, and provided the Gibbs energy DeltaG. Arrhenius and Eyring plots afforded kinetic parameters, namely, energies of activation E(a), enthalpies of activation DeltaH( not equal), and entropies of activation DeltaS( not equal). The DeltaG values deduced from kinetic parameters match very well with the DeltaG values determined from thermodynamic parameters. In addition, whereas signal coalescence of pyridinium hydrogen atoms located next to the amide bond was observed at 205 K in the oscillating rotaxane and at 203 K in the two-station rotaxane with a unique location of the macrocycle around the pyridinium amide, no separation of (1)H NMR signals of the considered hydrogen atoms was seen in the corresponding nonencapsulated thread. It is suggested that the macrocycle acts as a molecular brake for the rotation of the pyridinium-amide bond when it interacts by hydrogen bonding with both the amide NH and the pyridinium hydrogen atoms at the same time.

Designed Molecular Switches: Controlling the Conformation of Benzamido-diphenylacetylenes

With the goal of creating a molecular switch, the hydrogen-bonded diphenylacetylene structure has been modified such that an equilibrium now exists between two intramolecular H-bonded states. Through X-ray crystallography and (1)H NMR analysis it is shown that this equilibrium can be biased in a predictable manner by modulating the relative acidity of the amide NH's.

A Cyclopeptide‐Derived Molecular Cage for Sulfate Ions That Closes with a Click

The 2:1 sandwich-type complexes formed between a cyclopeptide with alternating L-proline and 6-aminopicolinic acid subunits and inorganic anions can be stabilized by covalently linking a tris-alkyne and a tris-azide derivative of this peptide through copper-catalyzed azide-alkyne cycloaddition. The resulting triply linked bis-cyclopeptide can interact with anions such as sulfate ions in aqueous solution by including them into the cavity between the two cyclopeptide rings, where they can form hydrogen bonds to amide NH groups, distributed along the inner surface. The binding kinetics of this system differ significantly from those of a bis-cyclopeptide that contains only one linker because the rate of guest exchange is considerably slower. Thermodynamically, the stability of the sulfate complex of the triply linked bis-cyclopeptide approaches a log K(a) value of 6 in H(2)O/CH(3)OH 1:1 (v/v) which is, however, only approximately one order of magnitude larger than affinity of the more flexible monolinked analogue. Titration calorimetry revealed that this behavior is mainly due to the change in the binding enthalpy from exothermic to endothermic upon increasing the number of linkers. Results from NMR spectroscopy and X-ray crystallography indicate that the mono- and triply linked bis-cyclopeptides adopt similar conformations in their complexes with sulfate ions, but the complex formation is enthalpically unfavorable for the cage. The substantial entropic contribution to sulfate complexation of this receptor more than compensates for this disadvantage, so that the overall sulfate affinity of both bis-cyclopeptides ends up in the same range. These investigations provide important insight into the structure-property relationships of such receptors, thus leading the way to further structural improvement.

ChemInform Abstract: Attempted Introduction of a Fourth Amide NH into the Carboxylate-Binding Pocket of Glycopeptide Antibiotics.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Synthesis and Evaluation of Chiral Selectors with Multiple Hydrogen-Bonding Sites in the Macrocyclic Cavities

Chiral macrocycles with the hydrogen bond donor/acceptor sites in the cavity were synthesized and covalently bonded to silica gel to give chiral stationary phases (CSPs), which showed excellent abilities to resolve various chiral compounds including ketones, esters, carboxylic acids, sulfoxides, amines, amino acid derivatives, and metal complexes. The effect of the linker connecting the macrocyclic moiety to silica was examined, and a more electronegative substituent was found to be better. Various organic solvents could be used as the mobile phase to optimize the resolution efficiency of the CSPs. Although the separation factors (alpha) tended to decrease with an increase in the solvent polarity, remarkable solvent tolerance was also observed. In some cases, even MeCN and MeOH could be used for the complete resolution of enantiomers. The MM calculations suggested that the chiral recognition of Co(acac)(3) is achieved by a combination of steric interactions and hydrogen bonds between the carbonyl O atom coordinated to the Co atom and the macrocyclic amide NH groups. The attachment of substituents to the 3,3'-positions of the binaphthyl moiety improved chiral HPLC performance in some cases. In particular, CSP-1d, having the Br atoms, showed the best performance for several analytes.

Synthesis and structure activity relationship studies of novel Staphylococcus aureus Sortase A inhibitors

Synthetic methods have been developed for lead Sortase A inhibitors identified from previous studies. Several derivatives of the lead inhibitor were synthesized to derive preliminary structure activity relationships (SAR). Different regions of the lead inhibitor that are critical for the enzyme activity have been determined by systematic SAR studies. The E stereochemistry of the lead compound was found to be critical for its activity. Replacement of the E double bond with Z double bond or a rigid triple bond reduced the enzyme inhibitory activity in most cases. Reduction of the double bond to a C–C single bond resulted in complete loss of activity. Amide carbonyl and NH groups were also found to be crucial for the activity of this class of inhibitors, as well. The morpholine ring oxygen atom was also found to be an important factor for the activity of the lead inhibitor. Preliminary SAR studies led to the identification of compounds with improved enzyme inhibition. The most active compound was found to have an IC 50 value of 58 μM against the enzyme.

Equilibrium Studies on the Gd3+, Cu2+ and Zn2+ Complexes of BOPTA, DTPA and DTPA‐BMA Ligands: Kinetics of Metal‐Exchange Reactions of [Gd(BOPTA)]2–

AbstractThe stability and protonation constants of the complexes formed between the ligand BOPTA [H5BOPTA: 4‐carboxy‐5,8,11‐tris(carboxymethyl)‐1‐phenyl‐2‐oxa‐5,8,11‐triazatridecan‐13‐oic acid] and Gd3+, Cu2+, and Zn2+ have been determined by pH potentiometry (Gd3+, Zn2+) and spectrophotometry (Cu2+) at 25 °C and at constant ionic strength maintained by 0.15 M NaCl. For comparison, the stability and protonation constants of the complexes of Gd3+, Cu2+, and Zn2+ formed with DTPA and DTPA‐BMA {H5DTPA: diethylenetriamine‐N,N,N′,N″,N″‐pentaacetic acid, H3DTPA‐BMA: 2,2′‐[(carboxymethyl)imino]bis[ethylenebis(methylcarbamoylmethyl)imino]diacetic acid} have also been determined under similar conditions. The stability constants (log KML) of the complexes of BOPTA and DTPA are very similar, but in 0.15 M NaCl the protonation constants of the ligands (log KiH) and the log KML values are lower than those obtained in 0.1 M KCl or Me4NCl by 0.3–0.9 log K units. The order of selectivity of the ligands for Gd3+ over Zn2+ is BOPTA > DTPA > DTPA‐BMA. The complex [Cu(DTPA‐BMA)]– deprotonates in the pH range 7–10 with the dissociation of an amide NH group and the coordination of the amide N atom. The kinetics of the exchange/transmetallation reactions between the complex [Gd(BOPTA)]2– and the metal ions Cu2+, Zn2+, and Eu3+ have been studied by spectrophotometry (Cu2+, Eu3+) and relaxometry (Zn2+) in the pH range 3.3–6 at 25 °C in 0.15 M NaCl. The reactions with Cu2+ and Zn2+ occur predominantly with direct attack of the metal ions on the [Gd(BOPTA)]2– complex. The kinetic activity of Eu3+ is lower, and in the exchange reactions with Eu3+, the proton‐assisted dissociation of [Gd(BOPTA)]2– (which is followed by fast reaction between the free ligand and Eu3+) could be also investigated. The rate constants, characterizing the proton‐assisted dissociation of [Gd(BOPTA)]2– and the exchange reactions occurring with the direct attack of Cu2+, Zn2+, and Eu3+ on the complex, are lower by about 30–90 % than the rate constants obtained earlier for similar transmetallation reactions of [Gd(DTPA)]2–. The half‐time for the dissociation of [Gd(BOPTA)]2– at pH 7.4 and at 25 °C in the presence of 1 × 10–5 M Zn2+ and 1 ×10–6 M Cu2+ is 169 h.

Assignment of the orphan nuclear receptor Nurr1 by NMR

The orphan nuclear receptor Nurr1 has been implicated in a number of conditions including Parkinson's disease and Schizophrenia. As such, it is of interest to study its interactions with other proteins, possibly mediated by small molecules, considering possible use as a drug target. We produced (2)H, (15)N, (13)C labelled-Nurr1 to generate the backbone amide NH, carbonyl C', C(alpha) and C(beta) assignments. About 84.0% of residues could be assigned. Most of the 37 missing assignments fall in 3 regions of the protein. Two of these surround a putative ligand-binding region of Nurr1, suggesting that this region of the protein is flexible, despite the ligand-binding pocket being filled with hydrophobic side-chains from residues surrounding the ligand binding pocket.

Recognition of Anions and Neutral Guests by Dicationic Pyridine-2,6-dicarboxamide Receptors

Dicationic N-methylated at pyridyl or quinolyl moieties derivatives of three isomers of N,N'-bis(pyridyl)pyridine-2,6-dicarboxamide (o-, m-, and p-1) and of N,N'-bis(3-quinolyl)pyridine-2,6-dicarboxamide (4) strongly bind anions in MeCN (log K in the range 3.5-6.5) with pronounced selectivity for Cl(-) and also bind neutral urea and amide guests with log K in the range 1.1-2.8. Crystal structures of the triflate salts of m-1, p-1, and 4 show that amide NH and pyridinium o-CH groups are directed inside the receptor cleft with their four protons forming a circle of radius ca. 2.35 A optimal for inclusion of Cl(-). The binding of anions to these protons is evident from the crystal structure of a mixed triflate/chloride salt of p-1, calculated (DFT/B3LYP 6-31G**) structures of 1:1 complexes of all receptors with Cl(-), and results of (1)H NMR titrations. In the crystal structure of o-1 pyridinium N-Me(+) groups are directed inside the receptor cleft impeding the anion complexation, but calculations demonstrate that simple rotation of pyridinium rings in opposite directions by ca. 30 degrees creates a cavity to which the Cl(-) ion can fit forming 4 hydrogen bonds to amide NH and aliphatic CH groups of N-Me(+). The results of (1)H NMR titrations confirm this type of binding in solution. Anions quench the intense fluorescence of 4, which allows their fluorescent sensing in the muM range. A new methodology for determination of anion binding constants to strongly acidic receptors by inhibitory effects of anions on the receptor deprotonation by an external base has been developed. High affinity and selectivity of anion complexation by dicationic pyridine-2,6-dicarboxamides is attributed to the rigid preorganized structure of receptors, the high acidity of NH and CH groups, and the electrostatic charge effect.

Dipeptide L -Seryl- L -Methionine—Linear Dichroic IR and Theoretical Characterization

ABSTRACT The dipeptide L -seryl- L -methionine is elucidated structurally by means of solid-state linear dichroic infrared spectroscopy of oriented samples as a colloidal suspension in nematic liquid crystal as a part of our systematic study of OH-containing small peptides. Vibrational analysis supports the experimental data as well. Quantum chemical ab initio calculations are performed in order to obtain the electronic structure and vibrational characteristics of the system studied, where a cisoide-configuration of the C=O–NH amide fragment is predicted.

Caste-specific tyramides from Myrmicine ants.

Analysis of the extracts of male ants of Monomorium minimum and Monomorium ebeninum by GC-MS and GC-FTIR revealed the presence of tyramides 2 and 4c, for which the structures were established by comparison with synthetic samples. These compounds and their analogues 1 and 3 were also found in males of other Monomorium species, males of Myrmicaria opaciventris, and males of several Solenopsis (Diplorhoptrum) species. Vapor-phase FTIR spectra revealed critically important structural clues to two of the tyramides, which had methyl branching in the tyramide acyl moiety. Tyramide 4c exhibited a strong intramolecular amide NH hydrogen bond where an alpha-keto group was deduced to be present in the acyl moiety and also showed the overlap of this ketone group frequency with that of the amide nu(C horizontal lineO). The biological function of these compounds is uncertain; however, their role in ant-mating behavior may be suggested by a large body of evidence.

Bis{2-hydroxy-N-[2-(2-pyridyl)ethyl]benzamide}copper(I) tetrafluoridoborate

The title complex, [Cu(C14H14N2O2)2]BF4, is a monomeric copper(I) species with linear two-coordinate geometry around the CuI atom. The asymmetric unit contains two half-cations that sit on crystallographic twofold rotation axes. The selected crystal was non-merohedrally twinned by a twofold rotation about an axis normal to the (100) family of planes. The ratio of the twin components refined to 0.4123 (6). Two 2-hydr­oxy-N-[2-(2-pyrid­yl)eth­yl]benzamide ligands coordinate to each CuI atom via the pyridyl N atom. Intra­molecular hydrogen bonding between the phenol OH groups and the amide O atoms imparts rigidity and planarity to the non-coordinating end of the ligand. The cationic complex is linked to the BF4 − anions via hydrogen bonding between the amide NH groups in the cations and BF4 − anions.

Generation and Analysis of Interaction Energy Maps of p-Substituted Benzoic Acid N'-(5-Nitrothiophen-2-yl)Methylenehydrazides Active Against Multidrug-Resistant Staphylococcus aureus

Studies in 3D molecular fields generally contain a large amount of data, some of which are redundant or not relevant. The program Volsurf, a quite fast method, is able to compress the relevant information present in 3D molecular structures into a few descriptors that represent the physicochemical properties. In this study eighteen p-substituted benzoic acid N-(5-nitrothiophen-2-yl)methylenehydrazides with antimicrobial activity were evaluated against multidrug-resistant Staphylococcus aureus, correlating the three-dimensional characteristics of the ligands with their respective bioactivities. Structures were obtained by CORINA program, and using a GRID force field, the following probes have been used to generate their corresponding 3D interaction energies (MIFs): water, DRY, carbonyl oxygen atom and amide NH group. Calculations using Volsurf resulted in a statistically consistent model with 48 structural descriptors showing that hydrophobicity is a fundamental property in the analyzed biological response. Results have shown the potential of studied compounds as alternatives to the treatment of infections caused by multidrug-resistant Staphylococcus aureus. Keywords: 3D QSAR, volsurf, nifuroxazide, MRSA, antimicrobials

Uncovering Individual Hydrogen Bonds in Rotaxanes by Frequency Shifts

We present a theoretical investigation of amide pseudorotaxane IR spectra in the harmonic approximation. In particular, we focus on the effect of axle substitution on the hydrogen bonds that are formed between axle and wheel. Two types of pseudorotaxanes are studied: one with the substituent affecting mostly the axle's carbonyl group and one with the effect influencing primarily the amide NH group. Sizeable red shifts are predicted for the carbonyl stretching frequencies, and large red shifts for the NH stretching frequencies. For the wheel amide groups involved in hydrogen bonding merely with their NH hydrogens, a small shift is observed for the carbonyl stretch mode. A clear relation is observed between the NH stretch shifts and individual hydrogen bond energies. This is confirmed by correlations of the shared electron number with the NH stretch shift showing that this quantity can be taken as an indicator for individual hydrogen bond energies. Axle substitution influences the strengths of the individual hydrogen bonds which is again reflected in the NH stretch frequency shifts. A linear relationship of Hammett's substituent parameters with the NH frequency shifts can be established.

Nanometer-Scale Water-Soluble Macrocycles from Nanometer-Sized Amino Acids

This paper introduces the unnatural amino acids m-Abc(2K) and o-Abc(2K) as nanometer-sized building blocks for the creation of water-soluble macrocycles with well-defined shapes. m-Abc(2K) and o-Abc(2K) are homologues of the nanometer-sized amino acid Abc(2K), which we recently introduced for the synthesis of water-soluble molecular rods of precise length (J. Am. Chem. Soc. 2007, 129, 7272). Abc(2K) is linear (180 degrees), m-Abc(2K) creates a 120 degree angle, and o-Abc(2K) creates a 60 degree angle. m-Abc(2K) and o-Abc(2K) are derivatives of 3'-amino-(1,1'-biphenyl)-4-carboxylic acid and 2'-amino-(1,1'-biphenyl)-4-carboxylic acid, with two propyloxyammonium side chains for water solubility. m-Abc(2K) and o-Abc(2K) are prepared as Fmoc-protected derivatives Fmoc-m-Abc(2K(Boc))-OH (1a) and Fmoc-o-Abc(2K(Boc))-OH (1b). These derivatives can be used alone or in conjunction with Fmoc-Abc(2K(Boc))-OH (1c) as ordinary amino acids in Fmoc-based solid-phase peptide synthesis. Building blocks 1a-c were used to synthesize macrocyclic "triangles" 9a-c, "parallelograms" 10a,b, and hexagonal "rings" 11a-d. The macrocycles range from a trimer to a dodecamer, with ring sizes from 24 to 114 atoms, and are 1-4 nm in size. Molecular modeling studies suggest that all the macrocycles except 10b should have well-defined triangle, parallelogram, and ring shapes if all of the amide linkages are trans and the o-alkoxy substituents are intramolecularly hydrogen bonded to the amide NH groups. The macrocycles have good water solubility and are readily characterized by standard analytical techniques, such as RP-HPLC, ESI-MS, and NMR spectroscopy. (1)H and (13)C NMR studies suggest that the macrocycles adopt conformations with all trans-amide linkages in CD(3)OD, that the "triangles" and "parallelograms" maintain these conformations in D(2)O, and that the "rings" collapse to form conformations with cis-amide linkages in D(2)O.