Amide NH Research Articles

Elucidation of penetration enhancement mechanism of Emu oil using FTIR microspectroscopy at EMIRA laboratory of SESAME synchrotron

It has been proposed that Emu oil possesses skin permeation-enhancing effect. This study aimed to address its possible penetration enhancement mechanism(s) using IR microscopy, in accordance with LPP theory. The penetration of Emu oil through the layers of human skin was accomplished by monitoring oil-IR characteristic feature at 3006cm−1. The unsaturated components of Emu oil accumulated at about 270μm depth of skin surface. The interaction of Emu oil with lipid and protein constituents of SC was investigated in comparison with a commonly used enhancer, IPM. Inter-sample spectral differences were identified using PCA and linked with possible enhancement mechanisms. Emu oil treatment caused a change in the slope of the right contour of amide I band of the protein spectral range. This was also clear in the second derivative spectra where the emergence of a new shoulder at higher frequency was evident, suggesting disorganization of keratin α-helix structure. This effect could be a result of disruption of some hydrogen bonds in which amide CO and NH groups of keratin are involved. The low intensity of the emerged shoulder is also in agreement with formation of weaker hydrogen bonds. IPM did not affect the protein component. No conclusions regarding the effect of penetration enhancers on the SC lipids were obtained. This was due to the overlap of the endogenous (skin) and exogenous (oil) CH stretching and scissoring frequencies. The SC carbonyl stretching peak disappeared as a result of IPM treatment which may reflect some degree of lipid extraction.

Reaction of (Z)-2-[3,3-dimethyl-3,4-dihydroisoquinolin-1(2H)-ylidene]-N-(2,4-dimethylphenyl)acetamides with ninhydrin

(Z)-2-[3,3-Dimethyl-3,4-dihydroisoquinolin-1(2Н)-ylidene]-N-(2,4-dimethylphenyl)acetamides react with ninhydrin at the β-carbon atom of the enamine and at the amide NH group.

Tertiary amine-catalyzed (3+3) annulations of δ-acetoxy allenoates: Substrate scope, synthetic application and mechanistic insight

Herein is reported the formal (3 + 3) annulations of δ-acetoxy allenoates with 1C,3O-bisnucleophiles by using 6’-deoxy-6’-perfluorobenzamido-quinine (5g) as the catalyst, providing rapid access to 4H-pyrans with excellent enantioselectivity. The reaction features wide substrate scope and mild reaction conditions. The utility of this method is demonstrated in highly stereoselective synthesis of the core of calyxin I. Mechanistic experiments suggest the involvement of 3-ammonium-2,4-dienoate intermediate BN. This type of cationic intermediate arises from an addition-elimination process between allenoate substrate and amine catalyst, and is stable enough for isolation and characterization. Mechanistic studies also disclose the crucial role of amide NH of 5g, which is able to not only activate allenoate to facilitate the formation of BN, but enhance the electrophilicity of δC of BN for nucleophilic attack.

Trityl Group as an Crystal Engineering Tool for Construction of Inclusion Compounds and for Suppression of Amide NH···O═C Hydrogen Bonds

It has been found that ditrityl derivatives of (R,R)-N,N′-cyclohexane-1,2-diyldiacetamide and their analogues invariably form crystals that possess inclusion properties. Enantiopurity of crystals is not a prerequisite for inclusion properties. The molecules form either two- or three-component inclusion compounds, in which hosts and guests are connected by hydrogen bonds specific for the included guest molecules but always involving the carbonyl groups of the host as acceptors. The association mode of the host molecules undergoes certain changes depending on the chemical modification of the host molecule, the type of included solvent molecule (protic/nonprotic), and whether the crystals are two- or three-component. Despite the potential for hydrogen bonding of the amide groups, no direct hydrogen bonding between the amide units of the host was observed in any of the reported structures allowing classification of a trityl group as a protection group of the amide N–H functionality in crystal engineering. X-r...

Enantioselective Synthesis of 4H-Pyran via Amine-Catalyzed Formal (3 + 3) Annulation of δ-Acetoxy Allenoate

The formal (3 + 3) annulations of δ-acetoxy allenoates and 1C,3O-bisnucleophiles are reported with the use of 6'-deoxy-6'-perfluorobenzamido-quinine (4g) as a catalyst, which provide rapid access to 4H-pyrans with excellent enantioselectivity. The reaction features a wide reaction scope and mild reaction conditions. The crucial roles of amide NH of 4g as a H-bond donor have also been elucidated, which not only activates allenoate to facilitate formation of cationic intermediate A but also enhances the electrophilicity of its δ-position for nucleophilic 1,6-addition.

Tetra-(meta-butylcarbamoyl)azobenzene: A Rationally Designed Photoswitch with Binding Affinity for Oxoanions in a Long-Lived Z-State.

A new photoswitchable anion receptor 1 based on a tetra-meta-substituted azobenzene skeleton has been readily synthesized in two steps. Titration studies (1H NMR) and theoretical predictions (DFT/M06-2X/6-31G(d)/DMSO-SM8) revealed that nonplanar Z-1 is a better host for anions than E-1, which results from the greater ability of four amide NH protons in the Z-state to cooperatively bind oxoanions, in particular tetrahedral H2PO4- and H2AsO4-. Furthermore, the thermal decay of Z-1 (τ1/2 = 11 days) is not accelerated by anion binding.

Electronic Effects of Aromatic Rings on the Catalytic Activity of Dioxidomolybdenum(VI)–Hydrazone Complexes

Nine dioxidomolybdenum(VI) complexes were synthesized through the reactions of MoO3 with tridentate hydrazone Schiff base ligands obtained from the reactions of aromatic acid hydrazides (3‐hydroxy‐2‐naphthoic acid hydrazide, 4‐pyridinecarboxylic acid hydrazide and 2‐furoic acid hydrazide) and ortho‐hydroxy aldehyde derivatives (5‐iodo‐2‐hydroxybenzaldehyde, 2‐hydroxy‐1‐naphthaldehyde and 2‐hydroxy‐3‐methoxybenzaldehyde). All of the ligands and complexes were characterized by elemental analysis and spectroscopic methods. The structures of seven complexes were further elucidated by single‐crystal X‐ray diffraction analysis, which indicated distorted octahedral geometries at the metal centres. Spectroscopic and X‐ray analyses indicated that the ligands are coordinated to the molybdenum(VI) ions as dianionic ligands owing to the deprotonation of the phenolic OH and amidic NH groups upon complexation. These complexes were used as catalysts for the oxidation of cyclooctene and thioanisole in the presence of hydrogen peroxide as an environmentally friendly oxidant. To achieve the highest catalytic activity, the effects of important parameters such as the solvent, temperature and molar ratio of the oxidant to the substrate were optimized. The results indicate that electron‐withdrawing substituents on the ligands increase the catalytic activities of dioxidomolybdenum(VI) hydrazone complexes.

Pyridine-incorporated cyclo[6]aramide for recognition of urea and its derivatives with two different binding modes

A novel pyridine-incorporated cyclo[6]aramide is designed and synthesised for recognition of urea and its derivatives. Analysis of its single crystal structure reveals the presence of introverted amide NH protons and amide carbonyl groups that are supposed to contribute to the subsequent accommodation of neutral urea-related guest molecules via multiple hydrogen bonding interactions. Thiourea is found to be superior to urea in binding to the receptor. Particularly interesting is the observation of two binding modes in complexing urea/thiourea (contact mode) and ethylurea/diethylurea (threading mode) as supported by both NMR experiments and computational simulations. The finding of the threading mode may open up new opportunities for the development of pesudorotaxanes and related mechanically interlocked structures.

Synthesis and NMR Analysis of a Conformationally Controlled β-Turn Mimetic Torsion Balance.

The molecular torsion balance concept was applied to a new conformationally controlled scaffold and synthesized to accurately evaluate pairwise amino acid interactions in an antiparallel β-sheet motif. The scaffold's core design combines (ortho-tolyl)amide and o,o,o'-trisubstituted biphenyl structural units to provide a geometry better-suited for intramolecular hydrogen bonding. Like the dibenzodiazocine hinge of the traditional torsion balance, the (ortho-tolyl)amide unit offers restricted rotation around an N-aryl bond. The resulting two-state folding model is a powerful template for measuring hydrogen bond stability between two competing sequences. The aim of this study was to improve the alignment between the amino acid sequences attached to the upper and lower aromatic rings in order to promote hydrogen bond formation at the correct distance and antiparallel orientation. Bromine substituents were introduced ortho to the upper side chains and compared to a control to test our hypothesis. Hydrogen bond formation has been identified between the NH amide proton of the upper side chain (proton donor) and glycine acetamide of the lower side chain (proton acceptor).

Oxoanion binding to a cyclic pseudopeptide containing 1,4-disubstituted 1,2,3-triazole moieties.

A macrocyclic pseudopeptide 3 is described featuring three amide groups and three 1,4-disubstituted 1,2,3-triazole units along the ring. This pseudopeptide was designed such that the amide NH groups and the triazole CH groups converge toward the cavity, thus creating an environment well suited for anion recognition. Conformational studies in solution combined with X-ray crystallography confirmed this preorganisation. Solubility of 3 restricted binding studies to organic media such as 5 vol% DMSO/acetone or DMSO/water mixtures with a water content up to 5 vol%. These binding studies demonstrated that 3 binds to a variety of inorganic anions in DMSO/acetone including chloride, nitrate, sulfate, and dihydrogenphosphate anions. In the more competitive DMSO/water mixtures, only affinity to the more strongly coordinating oxoanions is retained. Quantitative binding studies showed that dihydrogen phosphate complexation in DMSO/water involves the dimer of the H2PO4- anion. By contrast, sulfate and hydrogenpyrophosphate complexation involves a stepwise process comprising formation of a 1 : 1 complex followed by a 2R : 1A complex in which two molecules of 3 (R) bind to a single anion (A). While the second binding equilibrium is associated with a much smaller stability constant in comparison with the first one in the case of sulfate complexation, the two binding constants are of similar magnitude in the case of the hydrogenpyrophosphate anion. Formation of the 2R : 1A complex was attributed to the fact that the cavity size and rigidity of 3 prevents saturation of all hydrogen acceptor sites on the anionic guests.

Unpicking the determinants of amide NH⋯OC hydrogen bond strength with diphenylacetylene molecular balances

Hydrogen bonding plays an essential part in dictating the properties of natural and synthetic materials. Secondary amides are well suited to cross-strand interactions through the display of both hydrogen bond donors and acceptors and are prevalent in polymers such as proteins, nylon, and Kevlar™. In attempting to measure hydrogen bond strength and to delineate the stereoelectronic components of the interaction, context frequently becomes vitally important. This makes molecular balances - systems in which direct comparison of two groups is possible - an appealing bottom up approach that allows the complexity of larger systems to be stripped away. We have previously reported a family of single molecule conformational switches that are responsive to diverse stimuli including Brønsted and Lewis acids, anions, and redox gradients. In this work we assess the ability of the scaffold, based on a 2,6-disubstituted diphenylacetylene, to measure accurately the difference in hydrogen bond strength between variously functionalised amides. In all of the examples investigated hydrogen bond strength closely correlate to measures of Brønstead acidity suggesting that the scaffold is well-suited as a platform for the accurate determination of bond strength in variously substituted systems.

NMR Chemical Shift Mapping of SH2 Peptide Interactions.

Heteronuclear single quantum coherence (HSQC) nuclear magnetic resonance (NMR) experiments offer a rapid and high resolution approach to gaining binding and conformational insights into a protein-peptide interaction. By tracking 1H and 15N chemical shift changes over the course of a peptide titration into isotopically labeled protein, amide NH pairs of amino acids whose chemical environment changes upon peptide binding can be identified. When mapped onto a structure of the protein, this approach can identify the peptide-binding interface or regions undergoing conformation changes within a protein upon ligand binding. Monitoring NMR chemical shift changes can also serve as a screening technique to identify novel interaction partners for a protein or to determine the binding affinity of a weak protein-peptide interaction. Here, we describe the application of NMR chemical shift mapping to the study of peptide binding to the C-terminal SH2 domain of PLCγ1.

Partial structural studies of fucosylated chondroitin sulfate (FuCS) using attenuated total reflection fourier transform infrared spectroscopy (ATR-FTIR) and chemometrics

The compound fucosylated chondroitin sulfate from three sea cucumber species Holothuria atra, Stichopus horrens, and Holothuria arenicola was extracted and purified using strong ion exchange chromatography. The structure and sulfation patterns on their fucose branches were partially characterized and compared using liquid, gas chromatography-mass spectrometry, infrared spectroscopy, and chemometrics. The monosaccharide composition was consistently a 1:1 molar ratio of glucuronic acid to N-acetylgalactosamine while the fucose molar ratio was statistically different among the three species. Normal IR spectra exhibited a broad band at the region of 850–830cm−1 assigned to the sulfate COS group. This band was resolved in the second derivative spectra into two or three bands corresponding to the difference of sulfation patterns among sea cucumber species. Principal component analysis (PCA) confirmed the difference in the sulfate substitution region with additional discrimination of the combination amide NH and CO group, sulfate SO region, and skeletal region 1050–980cm−1. The hierarchical clustering analysis (HCA) successfully grouped each sea cucumber FuCS in the same cluster. Nevertheless, the comparison of the FuCS structure was simplified using chemometrics analysis.

Novel anion receptors for selective recognition of dimethyl phosphinate and carboxylate

We have designed and synthesized new anion receptors 1 and 2, which have amide NH, pyrrole NH and vinyl CH as hydrogen bond donors. These receptors are selective for dimethyl phosphinate and carboxylates. Due to electron withdrawing effect of the cyano group which is trans to the vinyl hydrogen with respect to carbon-carbon double bond, receptor 1 has higher binding constants for phosphinate and carboxylate than those of receptor 2. Modeling studies shows that cyano group polarized all three hydrogens through planar π-electron network. In addition, receptor 1 gave orange colored 1,4-addition product for cyanide.

A direct alkylation route to branched derivatives of suberoylanilide hydroxamic acid (SAHA), a potent non-selective inhibitor of histone deacetylases

Alkylation of malonamic esters provides a direct approach to derivatives of suberoylanilide hydroxamic acid (SAHA) that are branched at the amide carbon atom, a location pivotal for enhancing biological and therapeutic activity. Alkylations use NaH in THF followed by addition of the ester of 6-bromohexanoic acid; no protection of the amidic NH group is necessary. By this means, carboxylic acid, ester, amide, hydroxymethyl and 2-benzimidazolyl branching units have been appended to the SAHA backbone. Routes to vary one of the branching units at a time have been developed.

An insight into the photophysical properties of amide hydrogen bonded N-(benzo[d]thiazol-2-yl) acetamide crystals

Three distinct, hydrogen bond associated N-(benzo[d]thiazol-2-yl) acetamides were synthesized by refluxing benzothiazoles with acetic acid. The nature of the assemblies was characteristic to the substituent in the benzothiazole moiety. In N-(benzo[d]thiazol-2-yl)acetamide, water acts as a bridge for forming three hydrogen bonds, as an acceptor to amide NH, and donors to carbonyl of amide and thiazole nitrogen assembles of three different N-(benzo[d]thiazol-2-yl)acetamide molecules. The N-(6-methylbenzo[d]thiazol-2-yl)acetamide formed a (amide) N-H…N (thiazole) bonded R22(8) molecular dimers by two homo-intermolecular hydrogen bonding interactions. N-(6-methoxybenzo[d]thiazol-2-yl)acetamide formed (amide)N-H…O (acid) & (acid)O-H…N (thiazole) interactions with the acetic acid, forming a R22(8) hydrogen-bonded ring by two hetero-intermolecular hydrogen bonding interactions.

Reaction of ninhydrin with enamino amides of the 3,3-dimethyl-1,2,3,4-tetrahydroisoquinoline series and drotaverine

“Push–pull” enamines of the 1,2,3,4-tetrahydroisoquinoline series, 2-(3,3-dimethyl-1,2,3,4-tetrahydroisoquinolin- 1-ylidene)acetamides, reacted as 1,3-binucleophiles with ninhydrin to form tricyclic tetrahydroindeno[1,2-b]pyrrole system. The nucleophilic centers in the enamines were the amide NH2 group and s-carbon atom of the enamine fragment. The reaction of ninhydrin with 2-[2,2-dimethyl-2,3-dihydrobenzo[f]-isoquinolin-1(4H)-ylidene]-1-(pyrrolidin-1-yl)ethanone involved only addition to the s-carbon atom of the enamine fragment. The different reaction directions were rationalized by steric effect of two methyl groups in position 3 of the isoquinoline ring. The Knoevenagel condensation product was obtained by the reaction of ninhydrin with drotaverine (base). The structure of the 1,3-addition product, (3aS,8bS,Z)-{2,2-dimethyl-2,3- dihydrobenzo[f]isoquinolin-4(1H)-ylidene}-3a,8b-dihydroxy-1,3,3a,8b-tetrahydroindeno[1,2-b]pyrrole-2,4-dione, was confirmed by X-ray analysis.

Amine-Catalyzed Asymmetric (3 + 3) Annulations of β'-Acetoxy Allenoates: Enantioselective Synthesis of 4H-Pyrans.

The asymmetric (3 + 3) annulations of β'-acetoxy allenoates with either 3-oxo-nitriles or pyrazolones have been realized by using 6'-deoxy-6'-[(l)-N,N-(2,2'-oxidiethyl)-valine amido]quinine (6h) as the catalyst. The three functions of catalyst 6h, including Lewis base (quinuclidine N), H-bond donor (amide NH), and Brønsted base (morpholine N), cooperatively take crucial roles on the chemo- and enantioselectivity, allowing for the construction of 4H-pyran and 4H-pyrano[2,3-c]pyrazole in high yields and enantioselectivity.

ChemInform Abstract: Redox‐Neutral Couplings Between Amides and Alkynes via Cobalt(III)‐Catalyzed C—H Activation.

C–H activation assisted by a bifunctional directing group has allowed the construction of heterocycles. This is ideally catalyzed by earth-abundant and eco-friendly transition metals. We report Co(III)-catalyzed redox-neutral coupling between arenes and alkynes using an NH amide as an electrophilic directing group. The redox-neutral C–H activation/coupling afforded quinolines with water as the sole byproduct.

Crystal structure of 3-benzamido-1-(4-nitro-benz-yl)quinolinium tri-fluoro-methane-sulfonate.

In the title compound, C23H18N3O3 (+)·CF3SO3 (-), the asymmetric unit contains two crystallographically independent organic cations with similar conformations. Each cation shows a moderate distortion between the planes of the amide groups and the quinolinium rings with dihedral angles of 14.90 (2) and 31.66 (2)°. The quinolinium and phenyl rings are slightly twisted with respect to each other at dihedral angles of 6.99 (4) and 8.54 (4)°. The tri-fluoro-methane-sulfonate anions are linked to the organic cations via N-H⋯O hydrogen-bonding inter-actions involving the NH amide groups. In the crystal, the organic cations are linked by weak C-H⋯O(nitro group) inter-actions into supramol-ecular chains propagating along the b-axis direction.