Amide Nitrogen Atom Research Articles

Supramolecular architecture constructed from the hemidirected lead(II) complex with N'-(4-hydroxybenzylidene)isonicotinohydrazide

In this work we have directed our attention to the N'-(4-hydroxybenzylidene)isonicotinohydrazide (HL) as a linker for the production of a Pb(II) extended structure. As a result, discrete homoleptic coordination compound [PbL2] with two deprotonated ligands L was isolated. All the covalent PbN/O bonds are collected on a half of hemisphere of the globe of the coordination sphere yielding a large gap in the coordination sphere of Pb(II). This enables a close approach of the amide nitrogen atom from an adjacent molecule with the formation of a tetrel bond of about 3.0 Å, yielding 1D polymeric chains. These chains are interlinked via intermolecular OH⋯N hydrogen bonds and CH⋯π interactions, yielding a 3D structure. Considering OH⋯N intermolecular hydrogen bonds, molecules of [PbL2] form a single helical structural unit of a hexagonal shape. These motifs are mutualy interpenetrated and the overall 3D network of [PbL2] belongs to a ThSi2 network. The Pb⋯N tetrel bonding interaction was stiduied in details using DFT.

Triplet of cysteines – Coordinational riddle?

Polythiol binding of metal ions plays crucial role in the proper functioning of cysteine-rich proteins that are responsible for metal homeostasis and defending processes against metal toxicity (including heavy metals detoxification). The coordination properties of cysteine residues involved in specific sequencional patterns in proteins (like those present in e.g. metallothioneins) are interesting not only from a chemical point of view but may also lead to a better understanding of the purpose and allocation of metal ions in various biomolecules. In this study, the interaction of Zn2+, Cd2+ and Ni2+ ions with four peptides containing cysteine triplet motif were studied by potentiometric and spectroscopic methods. The main goal of this research was to answer the question how effectively three thiols, each being next to other, are able to bind single metal ion. Two of peptides contain additional, fourth cysteine residue, separated from triplet by two and three other amino acid residues. As results show, all three cysteine residues in the CCC motif are able to participate in the coordination of the metal ion (Cd2+, Zn2+). Except cysteine thiol groups, amide nitrogen atoms are also involved in the coordination of Ni2+.

Dinuclear Molybdenum(II) Complexes with Thioether Functionalized Silylamide Ligands

Treatment of molybdenum(II) acetate with thioether functionalized silylamides R2Si(NLi‐C6H4–2‐SR')2 leads to the formation of dinuclear MoII complexes [Mo2{R2Si(NC6H4‐2‐SR')2}2]. According to X‐ray crystal structure analyses the complexes [Mo2{Me2Si(NC6H4‐2‐SMe)2}2] and [Mo2{Ph2Si(NC6H4‐2‐SPh)2}2] comprise a Mo2‐unit which is coordinated by two μ‐κ‐N,N' silylamide ligands. The coordination sphere around the molybdenum atoms consists of two amide nitrogen atoms and two thioether sulfur atoms in a distorted square‐planar arrangement. The Mo‐Mo distances are 211.0(1) and 211.7(1) pm, resp. In the complex [Mo2{Ph2Si(NC6H4‐2‐SMe)2}2] the silyl amide units act as tetradentate κ‐N,N',S,S'chelating ligands and the Mo‐Mo distance is 218.6(1) pm.

Isolation and characterization of zinc-binding peptides from mung bean protein hydrolysates

The aim of this study was to isolate, purify, and characterize a novel peptide with zinc-binding ability from mung bean protein hydrolysates obtained by alcalase. The peptide purification process was performed using ultrafiltration, TSK-GEL size-exclusion chromatography, and reversed-phase high-performance liquid chromatography (RP-HPLC). The molecular weight of the isolated peptide was determined by liquid chromatography–electrospray ionization mass spectrometry (LC–ESI/MS) and found to be 1192.56 Da with amino acid sequence SSEDQPFNLR. The identified peptide showed zinc-binding capacity of 80.82 mg/g, which is 55.09% higher than that of the original mung bean protein hydrolyzate. Moreover, UV–vis and FTIR spectra indicated that the zinc-binding sites on the peptide were nitrogen atoms of amide, terminal amino group, and oxygen atoms on the carboxyl group. Moreover, zinc-releasing experiments showed that the peptide–zinc chelate is highly soluble under both acidic and alkaline conditions. Furthermore, the identified peptide significantly promoted the transportation and absorption of zinc ions in Caco-2 cell model. These findings indicate a potential for production of zinc-binding peptide from mung bean protein for the utilization as ingredient in functional foods.

Synthesis of naphtho[1,2‐b]‐, naphtho[2,1‐b]‐, and naphtho[2,3‐b]azepinones via proton‐induced cyclization of N‐1(2)‐naphthyl styrylacetamides

AbstractOn heating in polyphosphoric acid, N‐1‐naphthyl styrylacetamides undergo proton‐induced intramolecular cyclization at position 2 of the naphthyl ring to provide 5‐aryl‐1,3,4,5‐tetrahydro‐2Н‐naphtho[1,2‐b]azepin‐2‐ones, while their N‐2‐naphthyl analogues, when similarly reacted, are cyclized at positions 1 and 3 of the naphthyl ring and at the amide nitrogen atom leading, respectively, to 1‐aryl‐1,2,3,5‐tetrahydro‐4Н‐naphtho[2,1‐b]azepin‐4‐ones, 5‐aryl‐1,3,4,5‐tetrahydro‐2Н‐naphtho[2,3‐b]azepin‐2‐ones, and 5‐aryl‐1‐(2‐naphthyl)pyrrolidin‐2‐ones.

Azo Coupling of Enamino Amides of the 3,3-Dimethyl-1,2,3,4-tetrahydroisoquinoline Series with Arenediazonium Salts

The azo coupling of arenediazonium chlorides with (Z)-2-(3,3-dimethyl-3,4-dihydroisoquinolin-1(2H)-ylidene)-N-(4-methylphenyl)acetamide afforded (Z)-2-(2-arylhydrazinylidene)-2-(3,3-dimethyl-3,4-dihydroisoquinolin-1-yl)-N-(4-methylphenyl)acetamides whose structure was confirmed by 1H NMR and X-ray diffraction data. The azo coupling products containing no p-tolyl substituent on the amide nitrogen atom exist in solution as mixtures of azo and hydrazone tautomers. Electronic absorption spectra of the synthesized compounds were studied.

Crystal structures of two bis-carbamoyl-methyl-phosphine oxide (CMPO) compounds.

Two bis-carbamoyl-methyl-phosphine oxide compounds, namely {[(3-{[2-(di-phen-yl-phosphino-yl)ethanamido]-meth-yl}benz-yl)carbamo-yl]meth-yl}di-phenyl-phos-phine oxide, C36H34N2O4P2, (I), and diethyl [({2-[2-(di-eth-oxy-phosphino-yl)ethanamido]-eth-yl}carbamo-yl)meth-yl]phospho-nate, C14H30N2O8P2, (II), were synthesized via nucleophilic acyl substitution reactions between an ester and a primary amine. Hydrogen-bonding inter-actions are present in both crystals, but these inter-actions are intra-molecular in the case of compound (I) and inter-molecular in compound (II). Intra-molecular π-π stacking inter-actions are also present in the crystal of compound (I) with a centroid-centroid distance of 3.9479 (12) Å and a dihedral angle of 9.56 (12)°. Inter-molecular C-H⋯π inter-actions [C⋯centroid distance of 3.622 (2) Å, C-H⋯centroid angle of 146°] give rise to supra-molecular sheets that lie in the ab plane. Key geometric features for compound (I) involve a nearly planar, trans-amide group with a C-N-C-C torsion angle of 169.12 (17)°, and a torsion angle of -108.39 (15)° between the phosphine oxide phospho-rus atom and the amide nitro-gen atom. For compound (II), the electron density corresponding to the phosphoryl group was disordered, and was modeled as two parts with a 0.7387 (19):0.2613 (19) occupancy ratio. Compound (II) also boasts a trans-amide group that approaches planarity with a C-N-C-C torsion angle of -176.50 (16)°. The hydrogen bonds in this structure are inter-molecular, with a D⋯A distance of 2.883 (2) Å and a D-H⋯A angle of 175.0 (18)° between the amide hydrogen atom and the P=O oxygen atom. These non-covalent inter-actions create ribbons that run along the b-axis direction.

Highly Efficient N-Pivot Tripodal Diglycolamide Ligands for Trivalent f-Cations: Synthesis, Extraction, Spectroscopy, and Density Functional Theory Studies.

A series of four N-pivot tripodal diglycolamide (DGA) ligands, where three DGA moieties are attached to the central N atom via spacers of different lengths and with varying alkyl substituents on the amidic nitrogen of DGA (LI-LIV), were studied for their extraction and complexation ability toward trivalent lanthanide/actinide ions, including solvent extraction, complexation using spectrophotometric titrations, and luminescence spectroscopic studies. Introduction of a methyl group on the amidic nitrogen atom gives rise to a 400 fold increase of the Eu distribution ( D) value [LIII (NMe) vs LII (NH)] at 1 M HNO3. Enlargement of the spacer length between the pivotal N atom and the DGA moieties with one carbon atom results in a 14 times higher DEu value [LI (C3) vs LII (C2)]. Slope analyses showed that Eu3+ was extracted as a bis-solvated species with all four ligands. The compositions of the Eu3+/L complexes were further confirmed by spectroscopic measurements, its formation constants following the order: LIII > LIV > LI > LII. Luminescence spectroscopy and electrospray ionization mass spectrometry revealed that all four ligands form [Eu(L)2(NO3)3] complexes. Density functional theory and thermodynamic parameters corroborated the existence of [Eu(L)2(NO3)3] complexes.

Electrochemical Difluoromethylation of Electron-Deficient Alkenes.

Electrochemical 1,2-hydroxydifluoromethylation and C-H difluoromethylation of acrylamides were developed by using CF2 HSO2 NHNHBoc as the source of the CF2 H group. These electricity-powered oxidative alkene functionalization reactions do not need transition-metal catalysts or chemical oxidants. The reaction outcome, 1,2-difuntionalization or C-H functionalization, is determined by the substituents on the amide nitrogen atom of the acrylamides instead of by the reaction conditions.

Synthesis of New Bis(spiro-β-lactams) via Interaction of Methyl 1-Bromocycloalcanecarboxylates with Zinc and N,N′-Bis(arylmethylidene)benzidines

Interaction of the Reformatsky reagents, prepared from methyl 1-bromocyclopentane-1-carboxylate or methyl 1-bromocyclohexane-1-carboxylate, with N,N′-bis(arylmethylidene)benzidines has given rise to a set of intermediates as a result of nucleophilic addition to the C=N group of a substrate. Further intramolecular attack of the amide nitrogen atom onto the ester carbonyl group is responsible for the ring closure, which affords two series of spirocompounds: 2,2′-([1,1′-biphenyl]-4,4′-diyl)bis(3-aryl-2-azaspiro[3.4]octan-1-one) or 2,2′-([1,1′-biphenyl]-4,4′-diyl)bis(3-aryl-2-azaspiro[3.5]nonan-1-ones).

Amide nitrogen pyramidalization changes lactam amide spinning

Although cis-trans lactam amide rotation is fundamentally important, it has been little studied, except for a report on peptide-based lactams. Here, we find a consistent relationship between the lactam amide cis/trans ratios and the rotation rates between the trans and cis lactam amides upon the lactam chain length of the stapling side-chain of two 7-azabicyclo[2.2.1]heptane bicyclic units, linked through a non-planar amide bond. That is, as the chain length increased, the rotational rate of trans to cis lactam amide was decreased, and consequently the trans ratio was increased. This chain length-dependency of the lactam amide isomerization and our simulation studies support the idea that the present lactam amides can spin through 360 degrees as in open-chain amides, due to the occurrence of nitrogen pyramidalization. The tilting direction of the pyramidal amide nitrogen atom of the bicyclic systems is synchronized with the direction of the semicircle-rotation of the amide.

Reaction mechanism of the bioluminescent protein mnemiopsin1 revealed by X-ray crystallography and QM/MM simulations

Bioluminescence of a variety of marine organisms, mostly cnidarians and ctenophores, is carried out by Ca2+-dependent photoproteins. The mechanism of light emission operates via the same reaction in both animal families. Despite numerous studies on the ctenophore photoprotein family, the detailed catalytic mechanism and arrangement of amino acid residues surrounding the chromophore in this family are a mystery. Here, we report the crystal structure of Cd2+-loaded apo-mnemiopsin1, a member of the ctenophore family, at 2.15 Å resolution and used quantum mechanics/molecular mechanics (QM/MM) to investigate its reaction mechanism. The simulations suggested that an Asp-156-Arg-39-Tyr-202 triad creates a hydrogen-bonded network to facilitate the transfer of a proton from the 2-hydroperoxy group of the chromophore coelenterazine to bulk solvent. We identified a water molecule in the coelenteramide-binding cavity that forms a hydrogen bond with the amide nitrogen atom of coelenteramide, which, in turn, is hydrogen-bonded via another water molecule to Tyr-131. This observation supports the hypothesis that the function of the coelenteramide-bound water molecule is to catalyze the 2-hydroperoxycoelenterazine decarboxylation reaction by protonation of a dioxetanone anion, thereby triggering the bioluminescence reaction in the ctenophore photoprotein family.

Synthesis of tailored bis-succinamides and comparison of their extractability for U(VI), Th(IV) and Eu(III)

Nine tailored extractants containing bis-succinamide (BisSCA) skeleton have been synthesized and identified by NMR and HRMS. The extraction of U(VI), Th(IV) and Eu(III) using the present extractants was evaluated in nitric acid solution. The effect of alkyl groups attached to either the central or terminal nitrogen atoms of amide was investigated in view of the extraction efficiency. The results of slope analyses (logD vs. log[BisSCA]) suggested the formation of major complexed UO2(NO3)2·(BisSCA) species. ESI-MS spectrum further confirmed that BisSCA extractant formed 1:1 complex with uranyl ion. FT-IR spectra before and after the extraction also revealed that CO groups and COC group of ligand participated in complex reaction of uranyl cation. The comparative extraction of U(VI), Th(IV) and Eu(III) demonstrated that good separation factors were obtained in 132.6 for U/Eu and 166.6 for Th/Eu.

Crystal structure and Hirshfeld surface analysis of N,N'-bis-(2-nitro-phen-yl)glutaramide.

The asymmetric unit of the title compound, C17H16N4O6, contains two independent mol-ecules (A and B). The two benzene rings are twisted by an angle of 79.14 (7)° in mol-ecule A, whereas, in mol-ecule B, they are inclined by 19.02 (14)°. The conformations of the mol-ecules are stabilized by intra-molecular N-H⋯O hydrogen bonds between the amide nitro-gen atom and the O atom of the ortho-nitro substituent on the phenyl ring, enclosing an S(6) ring motif. In the amide and aliphatic segments, all the N-H, C=O and C-H bonds are anti to each other. In the crystal, the A and B mol-ecules are linked by inter-molecular amide-to-amide N-H⋯O hydrogen bonds, resulting in chains running along the b-axis direction. The inter-molecular inter-actions were analysed using Hirshfeld surface analysis. The two-dimensional fingerprint plots of the inter-molecular contacts indicate that the major contributions are from H⋯H and O⋯H inter-actions.

Unexpected Resistance to Base-Catalyzed Hydrolysis of Nitrogen Pyramidal Amides Based on the 7-Azabicyclic[2.2.1]heptane Scaffold.

Non-planar amides are usually transitional structures, that are involved in amide bond rotation and inversion of the nitrogen atom, but some ground-minimum non-planar amides have been reported. Non-planar amides are generally sensitive to water or other nucleophiles, so that the amide bond is readily cleaved. In this article, we examine the reactivity profile of the base-catalyzed hydrolysis of 7-azabicyclo[2.2.1]heptane amides, which show pyramidalization of the amide nitrogen atom, and we compare the kinetics of the base-catalyzed hydrolysis of the benzamides of 7-azabicyclo[2.2.1]heptane and related monocyclic compounds. Unexpectedly, non-planar amides based on the 7-azabicyclo[2.2.1]heptane scaffold were found to be resistant to base-catalyzed hydrolysis. The calculated Gibbs free energies were consistent with this experimental finding. The contribution of thermal corrections (entropy term, –TΔS‡) was large; the entropy term (ΔS‡) took a large negative value, indicating significant order in the transition structure, which includes solvating water molecules.

Study of metal-lipopeptide complexes and their self-assembly behavior, micelle formation, interaction with bovine serum albumin and biological properties

The present study aimed to explore the interactions of divalent counterions with biomolecular amphisin using circular dichroism (CD), ultraviolet–visible (UV–Vis) and density functional theory (DFT). The binding mode of interactions between metal-amphisin complexes and bovine serum albumin (BSA) were studied using fluorescence spectroscopy. The results showed that Cu2+ is coordinated by one oxygen atom of the aspartic acid side chain and three amide nitrogen atoms, whereas Zn2+, Ca2+ and Mg2+ favour the association with backbone oxygen atoms of the amphisin. On the other hand, the aggregation of amphisin induced by divalent counterions was studied by dynamic light scattering (DLS). Our results revealed that the self-assembly process of amphisin can be controlled by the addition of metal ions. The results of CD spectra demonstrated that the binding of divalent counterions to the lipopeptide induces conformational changes in amphisin. Further studies using fluorescence spectroscopy showed that the metal-lipopeptide systems could interact with some functional groups of BSA, increasing the microenvironment around Trp residues of BSA. Thus, the interaction data acquired herein for the interesting class of complexes will be of significance in metal-based drug discovery and developmental research.

Copper-Catalyzed Silylation of C(sp3)-H Bonds Adjacent to Amide Nitrogen Atoms.

A copper-catalyzed C-Si bond formation between N-halogenated amides and Si-B reagents is described. This oxidative coupling enables the silylation of C(sp3)-H bonds α to an amide nitrogen atom. The utility of the new method is demonstrated for sulfonamides, and N-chlorination with tBuOCl and C-H silylation employing CuSCN/4,4'-dimethoxy-2,2'-bipyridine as catalyst can be performed without purification of the N-Cl intermediate.

Doxycycline hydrate and doxycycline hydrochloride dihydrate – crystal structure and charge density analysis

Abstract High-resolution low-temperature X-ray diffraction experiments for doxycycline monohydrate and hydrochloride dihydrate have been performed. Translation-Libration-Screw (TLS) analysis for both crystal forms as well as the data from neutron diffraction experiment for hydrochloride combined with the Hansen-Coppens formalism resulted in precise charge density distribution models for both the zwitterionic monohydrate and a protonated hydrochloride crystal forms. Their detailed topological analysis suggested that the electron structure of doxycycline’s amide moiety undergoes significant changes during protonation due to formation of a very strong resonance-assisted hydrogen bond. A notably increased participation of amide nitrogen atom and hydrogen-accepting oxygen atom in the resonance upon doxycycline protonation was observed. A comparison of TLS- and neutron data-derived hydrogen parameters confirmed the experimental neutron data to be vital for proper description of intra- and inter-molecular interactions in this compound. Finally, calculated lattice and interaction energies quantified repulsive Dox-Dox interactions in the protonated crystal form of the antibiotic, relating with a good solubility of doxycycline hydrochloride relative to its hydrate.

Reaction of Amides of Sulfanyl, Thio-, and Carbonic Acids with Tropylium Salts

By the reaction of urea, thiourea, sulfanilamide or sulfadimethoxine with tropylium tetrafluoroborate new products of substitution of hydrogen atom by the tropylium motif at the amide nitrogen atom or at the amino group of the benzene ring have been obtained.

Heteroatom‐Interchanged Isomers of Lissoclinamide 5: Copper(II) Complexation, Halide Binding, and Biological Activity

Cyclic peptides, especially those produced by marine cyanobacteria symbionts, are considered to play an important ecological role in host defence. Chemists have long compared the cyclic peptide cavitand architecture with that of macrocyclic ligands, and proposed that they mediate metal‐ion transport. The study presented herein investigated the metal chelation of non‐natural heteroatom‐interchanged (HI) isomers of lissoclinamide 5, by using MS, EPR, and DFT calculations. The latter identified three possible structures for the CuII complex with natural lissoclinamide 5, with the most likely determined to be that with the metal ion bound through the nitrogen donors of the thiazoles and one deprotonated amide. For HI‐lissoclinamide 5 the calculations suggest that the CuII ion is bound in a bidentate manner by the oxazoline nitrogen atom and one deprotonated amide nitrogen atom, with the S donor of the thiazole not involved in coordination. Along with evidence of copper binding these systems also bound halide ions. Evaluation of the anti‐cancer properties demonstrated that the biological activity of HI‐lissoclinamide 5 against T24 bladder cells was eleven‐fold lower as compared to natural lissoclinamide 5. Addition of a CuII salt had no effect on the activity of lissoclinamide 5. Overall, this comprehensive study of the HI concept has demonstrated that small changes propagate dramatic effects in complexation, halide binding, and biological activity.