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Accurate determination of protein structure at interfaces is critical for understanding protein interactions, which is directly relevant to a molecular-level understanding of interfacial proteins in biology and medicine. Vibrational sum frequency generation (VSFG) spectroscopy is often used for probing the protein amide I mode, which reports protein structures at interfaces. Observed peak shifts are attributed to conformational changes and often form the foundation of hypotheses explaining protein working mechanisms. Here, we investigate structurally diverse proteins using conventional and heterodyne-detected VSFG (HD-VSFG) spectroscopy as a function of solution pH. We reveal that blue-shifts of the amide I peak observed in conventional VSFG spectra upon lowering the pH are governed by the drastic change of the nonresonant contribution. Our results highlight that connecting changes in conventional VSFG spectra to conformational changes of interfacial proteins can be arbitrary, and that HD-VSFG measurements are required to draw unambiguous conclusions about structural changes in biomolecules.

The binary intermolecular complexes of amides and formaldehyde can be taken as suitable models to investigate the non-covalent interactions of a peptide with the carbonyl group. We herein studied the rotational spectra of the model complexes of 2-azetidinone-H 2 CO and formamide-H 2 CO generated in a helium supersonic jet. For each complex, one rotational spectra featuring hyperfine structures caused by the 14 N quadrupole coupling effect was observed and assigned to its global minimum conformation. The detected isomers of both studied complexes are stabilized by a dominant amide hydrogen bond N-H⋯OC and a weaker C-H⋯O interaction, preferring the C s symmetry. NBO and SAPT analyses provide quantitative estimation of the non-covalent interactions stabilizing the complexes.

Vibrational sum frequency generation (vSFG) spectroscopy is widely used to probe the protein structure at interfaces. Because protein vSFG spectra are complex, they can only provide detailed structural information if combined with computer simulations of protein molecular dynamics and spectra calculations. We show how vSFG spectra can be accurately modeled using a surface-specific velocity-velocity scheme based on ab initio normal modes. Our calculated vSFG spectra show excellent agreement with the experimental sum frequency spectrum of LTα14 peptide and provide insight into the origin of the characteristic α-helical amide I peak. Analysis indicates that the peak shape can be explained largely by two effects: (1) the uncoupled response of amide groups located on opposite sides of the α-helix will have different orientations with respect to the interface and therefore different local environments affecting the local mode vibrations and (2) vibrational splitting from nearest neighbor coupling evaluated as inter-residue vibrational correlation. The conclusion is consistent with frequency mapping techniques with an empirically based ensemble of peptide structures, thus showing how time correlation approaches and frequency mapping techniques can give independent yet complementary molecular descriptions of protein vSFG. These models reveal the sensitive relationship between protein structure and their amide I response, allowing exploitation of the complicated molecular vibrations and their interference to derive the structures of proteins under native conditions at interfaces.

The putative interaction of a C-F bond with an amide carbonyl has been an intriguing topic of interest in this century for reasons spanning basic physical organic chemistry to biochemistry. However, to date, there exist no examples of a close, well-defined interaction in which its unique aspects can be identified and exploited. Herein, we finally present an engineered system possessing an exceptionally tight C-F-amide interaction, allowing us to obtain spectroscopic, crystallographic, and kinetic details of a distinctive, biochemically relevant chemical system for the first time. In turn, we also explore Lewis acid coordination, C-F bond promotion of amide isomerization, enantiomerization, and ion protonation processes., (© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

The dynamics and spectroscopy of N -methyl-acetamide (NMA) and trialanine in solution are characterized from molecular dynamics simulations using different energy functions, including a conventional point charge (PC)-based force field, one based on a multipolar (MTP) representation of the electrostatics, and a semiempirical DFT method. For the 1D infrared spectra, the frequency splitting between the two amide-I groups is 10 cm -1 from the PC, 13 cm -1 from the MTP, and 47 cm -1 from self-consistent charge density functional tight-binding (SCC-DFTB) simulations, compared with 25 cm -1 from experiment. The frequency trajectory required for the frequency fluctuation correlation function (FFCF) is determined from individual normal mode (INM) and full normal mode (FNM) analyses of the amide-I vibrations. The spectroscopy, time-zero magnitude of the FFCF C ( t = 0), and the static component Δ 0 2 from simulations using MTP and analysis based on FNM are all consistent with experiments for (Ala) 3 . Contrary to this, for the analysis excluding mode-mode coupling (INM), the FFCF decays to zero too rapidly and for simulations with a PC-based force field, the Δ 0 2 is too small by a factor of two compared with experiments. Simulations with SCC-DFTB agree better with experiment for these observables than those from PC-based simulations. The conformational ensemble sampled from simulations using PCs is consistent with the literature (including P II , β, α R , and α L ), whereas that covered by the MTP-based simulations is dominated by P II with some contributions from β and α R . This agrees with and confirms recently reported Bayesian-refined populations based on 1D infrared experiments. FNM analysis together with a MTP representation provides a meaningful model to correctly describe the dynamics of hydrated trialanine.

Understanding the structure and chemistry of nanoscopic surfaces is an important challenge for biointerface sciences. Sum frequency scattering (SFS) spectroscopy can specifically probe the surfaces of nanoparticles, vesicles, liposomes, and other materials relevant to biomaterial research, and, as a vibrational spectroscopy method, it can provide molecular level information about the surface chemistry. SFS is particularly promising to probe the structure of proteins, and other biological molecules, at nanoparticle surfaces. Here, amide I spectra can provide information about protein folding and orientation, while spectra in the C-D and C-H stretching regions allow experiments to determine the mode of interaction between particle surfaces and proteins. Methods used currently employ a closed liquid cell or cuvette, which works extremely well for C-H and phosphate regions but is often impeded in the amide I and C-D regions by a strong background signal that originates from the window material of the sample cells. Here, we discuss a windowless geometry for collecting background-free and high-fidelity SFS spectra in the amide I and C-D regions. We demonstrate the improvement in spectra quality by comparing SFS spectra of unextruded, multilamellar vesicles in a sample cuvette with those recorded using the windowless geometry. The sample geometry we propose will enable new experiments using SFS as a probe for protein-particle interactions.

n → π* has emerged as an important noncovalent interaction that can affect the conformations of both small- and macromolecules including peptides and proteins. Carbonyl-carbonyl (COCO) n → π* interactions involving CO groups are well studied. Recent studies have shown that the COCO n → π* interactions are the most abundant secondary interactions in proteins with a frequency of 33 interactions per 100 residues and, among the various secondary interactions, n → π* interactions are expected to provide the highest enthalpic contributions to the conformational stability of globular proteins. However, n → π* interactions are relatively weak and provide an average stabilization of about 0.25 kcal mol-1 per interaction in proteins. The strongest n → π* interaction could be as strong as a moderate hydrogen bond. Therefore, it is challenging to detect and quantify these weak interactions, especially in solution in the presence of perturbation from other intermolecular interactions. Accordingly, spectroscopic investigations that can provide direct evidence of n → π* interaction are limited, and the majority of papers published in this area have relied on X-ray crystallography and/or theoretical calculations to establish the presence of this interaction. The aim of this perspective is to discuss the studies where a spectroscopic signature in support of n → π* interaction was observed. As the "n → π* interaction" is a relatively new terminology, there remains the possibility of there being earlier studies where spectroscopic evidence for n → π* interactions was obtained but it was not discussed in light of the n → π* terminology. We noticed several such studies and, as can be expected, these studies were often overlooked in the discussion of n → π* interactions in the recent literature. In this perspective, we have also discussed these studies and provided computational support for the presence of n → π* interaction.

A series of disubstituted 1 H -pyrazoles with methyl ( 1 ), amino ( 2 ), and nitro ( 3 ) groups, as well as ester ( a ) or amide ( b ) groups in positions 3 and 5 was synthesized, and annular tautomerism was investigated using X-ray, theoretical calculations, NMR, and FT-IR methods. The X-ray experiment in the crystal state showed for the compounds with methyl ( 1a , 1b ) and amino ( 2b ) groups the tautomer with ester or amide groups at position 3 (tautomer 3), but for those with a nitro group ( 3b , 4 ), tautomer 5. Similar results were obtained in solution by NMR NOE experiments in CDCl 3 , DMSO- d 6 , and CD 3 OD solvents. However, tautomer equilibrium was observed for 2b in DMSO. The FT-IR spectra in chloroform and acetonitrile showed equilibria, which can be ascribed to conformational changes of the cis/trans arrangement of the ester/amide group and pyrazole ring. Theoretical analysis using the M06-2X/6-311++G(d,p) method (in vacuo, chloroform, acetonitrile, and water) and measurement of aromaticity (NICS) showed dependence on internal hydrogen bonds, the influence of the environment, and the effect of the substituent. These factors, pyrazole aromaticity and intra- and inter-molecular interactions, seem to have a considerable influence on the choice of tautomer.

The balance of lipid-peptide and peptide-peptide interactions at cell membrane is essential to a large variety of cellular processes. In this study, we have experimentally demonstrated for the first time that sum frequency generation vibrational spectroscopy can be used to probe the peptide-peptide and lipid-peptide interactions in cell membrane in situ and in real time by determination of the line width of amide I band of protein backbone. Using a "benchmark" model of α-helical WALP23, it is found that the dominated lipid-peptide interaction causes a narrow line width of the amide I band, whereas the peptide-peptide interaction can markedly broaden the line width. When WALP23 molecules insert into the lipid bilayer, a quite narrow line width of the amide I band is observed because of the lipid-peptide interaction. In contrast, when the peptide lies down on the bilayer surface, the line width of amide I band becomes very broad owing to the peptide-peptide interaction. In terms of the real-time change in the line width, the transition from peptide-peptide interaction to lipid-peptide interaction is monitored during the insertion of WALP23 into 1,2-dipalmitoyl- sn-glycero-3-phospho-(1'- rac-glycerol) (DPPG) lipid bilayer. The dephasing time of a pure α-helical WALP23 in 1-palmitoyl-2-oleoyl- sn-glycero-3-phospho-(1'- rac-glycerol) and DPPG bilayer is determined to be 2.2 and 0.64 ps, respectively. The peptide-peptide interaction can largely accelerate the dephasing time.

Since potential changes in the dynamics and mobility of drugs upon complexation for delivery may affect their ultimate efficacy, we have investigated the dynamics of two local anesthetic molecules, bupivacaine (BVC, C 18 H 28 N 2 O) and ropivacaine (RVC, C 17 H 26 N 2 O), in both their crystalline forms and complexed with water-soluble oligosaccharide 2-hydroxypropyl-β-cyclodextrin (HP-β-CD). The study was carried out by neutron scattering spectroscopy, along with thermal analysis, and density functional theory computation. Mean square displacements suggest that RVC may be less flexible in crystalline form than BVC, but both molecules exhibit very similar dynamics when confined in HP-β-CD. The use of vibrational analysis by density functional theory (DFT) made possible the identification of molecular modes that are most affected in both molecules by insertion into HP-β-CD, namely those of the piperidine rings and methyl groups. Nonetheless, the somewhat greater structure in the vibrational spectrum at room temperature of complexed RVC than that of BVC, suggests that the effects of complexation are more severe for the latter. This unique approach to the molecular level study of encapsulated drugs should lead to deeper understanding of their mobility and the respective release dynamics., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Three amide derivatives - methyl-2-[2-(4-isobutylphenyl)propanamido]propanoate (Dex-2), methyl 2-[2-(4-isobutylphenyl) propanamido]-3-phenylpropanoate (Dex-3) and methyl 2-[2-(4-isobutylphenyl)-propanamido]-4-methylpentanoate (Dex-4) of dexibuprofen (Dex-1) 2-(4-isobutylphenyl)propanoic acid were synthesized and conformed for structures by physical data and spectral analysis. Further, all the compounds were studied for their binding with ds.DNA through experimental (UV-visible/and fluorescence spectroscopy, cyclic voltammetry) and theoretical (molecular docking) techniques. Spectral and voltammetric responses as well as kinetic and thermodynamic data interpretations at stomach (4.7) and blood (7.4) pH and at human body temperature (37°C) indicated spontaneous interaction of all the compounds with DNA via intercalation and external bindings. The binding constants (K b ) and Gibbs free energy changes (-ΔG) were evaluated greater at pH7.4 attributing comparatively more significant binding of all the compounds with DNA at blood pH. Among all compounds, Dex-4 showed greater binding with DNA at both pH with greater K b values i.e., {UV-visible: pH 4.7 (2.36×10 4 M -1 ); pH7.4 (2.42×10 4 M -1 ), fluorescence: pH4.7 (2.24×10 4 M -1 ); pH7.4 (2.56×10 4 M -1 ) and CV: pH4.7 (4.06×10 4 M -1 ); pH7.4 (4.89×10 4 M -1 )}. Binding site size (n) at both pH values was evaluated n≥1 for Dex-2 and Dex-4 which assured intercalation as a major mode of interaction between compounds and DNA. For Dex-1 and Dex-3 (n) was evaluated n≤1 at both pH values and the values n<1 indicated the possibility of binding via groove or electrostatic interactions. Electrochemical processes were found diffusion controlled and diffusion coefficients (D o ) for all the compounds - DNA adducts were evaluated lesser than unbound compounds. Docking studies further supported DNA binding evidences obtained from spectral and electrochemical investigations., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The study of protein-surfactant interactions is important because of the widespread use of surfactants in industry, medicine, and pharmaceutical fields. Sodium N-lauroylsarcosinate (SL-Sar) is a widely used surfactant in cosmetics, shampoos. In this paper, we studied the interactions of bovine serum albumin (BSA) with SL-Sar and sodium N-lauroylglycinate (SL-Gly) by use of a number of techniques, including fluorescence and circular dichroism spectroscopy and isothermal titration calorimetry. The binding strength of SL-Sar is stronger than that of structurally similar SL-Gly, which differs only by the absence of a methyl group in the amide nitrogen atom. Also, these two surfactants exhibit different binding patterns with the BSA protein. The role of the amide bond and hence the surfactant headgroup in the binding mechanism is discussed in this paper. It was observed that while SL-Sar destabilized, SL-Gly stabilized the protein structure, even at concentrations less than the critical micelle concentration (cmc) value. The thermodynamics of surfactant binding to BSA was studied by use of ITC. From the ITC results, it is concluded that three molecules of SL-Sar in contrast to only one molecule of SL-Gly bind to BSA in one set of binding sites at room temperature. However, on increasing temperature four molecules of SL-Gly bind to the BSA through H-bonding and van der Waals interactions, due to loosening of the BSA structure. In contrast, with SL-Sar the binding process is enthalpy driven, and very little structural change of BSA was observed at higher temperature.

Gas-phase vibrational spectroscopy, coupled cluster (CCSD(T)), and dispersion corrected density functional (B97-D3) methods are employed to characterize surprisingly strong sulfur center H-bonded (SCHB) complexes between cis and trans amide NH and S atom of methionine and cysteine side chain. The amide N-H···S H-bonds are compared with the representative classical σ- and π-type H-bonded complexes such as N-H···O, N-H···O═C and N-H···π H-bonds. With the spectroscopic, theoretical, and structural evidence, amide N-H···S H-bonds are found to be as strong as the classical σ-type H-bonds, despite the smaller electronegativity of sulfur in comparison to oxygen. The strength of backbone-amide N-H···S H-bonds in cysteine and methionine containing peptides and proteins are also investigated and found to be of similar magnitudes as those observed in the intermolecular model complexes studied in this work. All such SCHBs also confirm that the electronegativities of the acceptors are not the sole criteria to predict the H-bond strength.

The vibrational properties of the amide-I modes of β-peptides in five helical conformations (8-helix, 10-helix, 12-helix, 14-helix, and 10/12-helix) from tetramer to heptamer were examined by ab initio calculations. The normal modes have been first decoupled into local modes, whose transition energies are found to be intrinsically sensitive to peptide structure and intramolecular hydrogen bonding interactions. By further removing the intramolecular hydrogen bonding interactions, pure local modes are obtained, whose transition energies still exhibit some conformational dependence in 8-helix and 10/12 hybrid helix, but not much in homogeneous 10-, 12-, and 14-helical conformations. This suggests that a set of nearly degenerated pure local-mode transitions can be specified when excitonic modeling the amide-I vibration in latter cases. The work provides important benchmark measurements for understanding the complexity of the amide-I absorption spectra of β-polypeptides.

The organocatalytic enantioselective conjugate addition of secondary β-ketoamides to α,β-unsaturated carbonyl compounds is reported. Use of bifunctional Takemoto's thiourea catalyst allows enantiocontrol of the reaction leading either to simple Michael adducts or spirocyclic aminals in up to 99 % ee. The origin of the enantioselectivity has been rationalised based on combined DFT calculations and kinetic analysis. This study provides a deeper understanding of the reaction mechanism, which involves a predominant role of the secondary amide proton, and clarifies the complex interactions occurring between substrates and the catalyst., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Four new ansamycin derivatives, named 1,19-epithio-geldanamycin A (1), 17-demethoxylherbimycin H (2), herbimycin M (3), and seco-geldanamycin B (4), together with eight known ansamycin analogues (5 – 12) were isolated from the solid fermentation of marine-derived actinomycete Streptomyces sp. ZYX-F-97. The structures of new compounds were elucidated by extensive spectroscopic analysis as well as nuclear magnetic resonance (NMR) and electronic circular dichroism (ECD) calculations. All the compounds were assayed for their antibacterial activity. Among them, compounds 4 , 8 , and 12 exhibited remarkable inhibition against Listeria monocytogenes with minimum inhibitory concentrations (MIC) values ranging from 8 μg·mL−1 to 64 μg·mL−1, and displayed moderate inhibition against methicillin-resistant Staphylococcus aureus (MRSA) with MIC value of 64 μg·mL−1. Compounds 4 , 8 , 9 , and 12 showed moderate inhibition activities against both Staphylococcus aureus and Bacillus subtilis with MIC values ranging from 32 μg·mL−1 to 128 μg·mL−1. [Display omitted] [ABSTRACT FROM AUTHOR]

The occurrence of macrocyclic daphnane orthoesters (MDOs) with a 1-alkyl group originating from a C 14 aliphatic chain is extremely limited in the plant kingdom and has only been isolated from Edgeworthia chrysantha. In the present study, LC-ESI-MS/MS analysis was performed on different parts of E. chrysantha , including flower buds, flowers, leaves, and stems, and resulted in the identification of seven MDOs in all the four plant parts, including two previously unreported compounds 1 and 7. Further LC-MS guided isolation was carried out to afford compounds 1 and 7 , and their structures were determined by various spectroscopic analyses. These compounds were also evaluated for anti-HIV activity, thus expanding insights into the structure-activity relationships for MDOs. [Display omitted] • Seven macrocyclic daphnane orthoesters were identified from Edgeworthia chrysantha by LC-ESI-MS/MS analysis. • ESI-MS/MS fragmentation of macrocyclic daphnane orthoesters was elucidated. • Two unreported compounds were isolated by LC-MS guided isolation. • Structures of isolated compounds were determined by various spectroscopic analyses. • Isolated compounds were evaluated for anti-HIV activity. [ABSTRACT FROM AUTHOR]

Abstract Interactions with water are one of the key factors which determine protein stability and activity in aqueous solutions. However, the protein hydration is still insufficiently understood. N -methylacetamide (NMA) is regarded as a minimal part of the peptide backbone and the relative simplicity of its structure makes it a good model for studies on protein–water interactions. In this paper, the influence of NMA and N,N -dimethylacetamide (DMA) on surrounding water molecules in a range of temperature (25–75 °C) is studied by means of the FTIR spectroscopy. The results of the difference HDO spectra method are compared with the results of theoretical DFT calculations of NMA and DMA aqueous complexes. Both NMA and DMA can be regarded as "structure-makers", yet their hydration spheres are different. These molecules exhibit a mixed and mutually dependent types of hydration: hydrophilic and hydrophobic. In the case of a NMA molecule that has one methyl group less than DMA, the type of hydrophobic hydration is more important. The DMA hydration sphere is less stable: the interactions between water molecules around the methyl groups are strained. Moreover, the hydration of NMA is much more temperature dependant than in the case of DMA. The source of the differences may be hidden in the N H⋯H 2 O interaction. The delicate nature of water interactions with the peptide block models may be cautiously translated into the much more complicated interactions of proteins with their hydration shells. [ABSTRACT FROM AUTHOR]

With the aim to develop highly potential active heterocyclic compounds, two series of multi-substituted pyrrolizinone and indolizinones derived from lactam were designed, synthesized and evaluated for their potential antifungal activities against six species of the plant pathogen fungi ( Fusarium graminearum, Sclerotinia sclerotiorum, Phomopsis adianticola, Gloeosporium theae-sinensis, Alternaria tenuis Nees, Magnaporthe oryzae ). The structure of all the newly molecules were confirmed by analytical spectroscopic data, including 1 H NMR, 13 C NMR and ESI-MS. According to the preliminary studies on bio-evaluation assay, some of the obtained compounds exhibited moderate and broad-spectrum activities against six fungi compared to the intermediates 6a , 6f and the hymexazol. Particularly, the inhibition rate of compounds 7l , 7m and 7t reached 69.25%, 74.76%, 65.38% against Phomopsis adianticola and Magnaporthe oryzae in vitro activity. Furthermore, compounds 7l and 7t displayed obviously inhibition activities against Phomopsis adianticola compared to the hymexazol. Consequently, compounds 7l and 7t with six-membered alkane ring could be used as new motifs for further investigation. [ABSTRACT FROM AUTHOR]

The amide derivatives were synthesized from isopimaric acid and characterized by spectroscopy. These amides were examined in vitro for their cytotoxic activity against four cancer cell lines. The majority of the screened compounds displayed better inhibitory activity than isopimaric acid, and many amides displayed promising cytotoxic activity against hepatocarcinoma (HepG-2), breast carcinoma (MDA-MB-231), and prostate adenocarcinoma (PC-3). It was found that the substituent type, number, and position in the benzene and heterocyclic rings have an important influence on cytotoxicity against the three tested cancer cell lines. [ABSTRACT FROM AUTHOR]

Two novel nitrogenous diterpenoids, sarinfacetamides A (1) and B (2), featuring an uncommon tricyclo[6.3.1.01,5]dodecane scaffold, and a known related diterpene (3) were isolated from the South China Sea soft coral Sarcophyton infundibuliforme. Their structures, including the absolute configuration of 1, were established by extensive spectroscopic analysis and TDDFT-ECD calculation. Compounds 1 and 3 exhibited interesting promotion effects on the ConA-induced T lymphocyte proliferation. A plausible biosynthetic pathway for 1 and 2 was also proposed. [ABSTRACT FROM AUTHOR]

Catalytic allylic γ‐substitution with Morita‐Baylis‐Hillman (MBH) adducts for creating a new family of unsymmetrical dicarbonyl compounds was presented in this work, in which a variety of allylated amide products were achieved in good yields and high regioselectivity with excellent linear‐to‐branched ratios. Especially, it was found that the Pd/HZNU‐Phos complex exhibited remarkably high activity (with a TON up to 16800) in this transformation between dicarbonyl amides and MBH adducts. In addition, the possibly multisite interaction between multifunctional Pd/HZNU‐Phos catalyst system and substrates might responsible for its exceptionally high efficiency in this reaction. [ABSTRACT FROM AUTHOR]

Four metalloporphyrin dimers linked by bridging amide-bonded xanthene moieties and that contain either MnIII, CoII, NiII, or CuII metal centers were synthesized. Various spectroscopic, electrochemical, and spectroelectrochemical methods were used to study trends in their properties. Their electronic structure and optical properties were analyzed through a comparison of the electronic absorption and magnetic circular dichroism (MCD) spectral data with the results of time-dependent (TD)-DFT calculations. [ABSTRACT FROM AUTHOR]

A new strategy to analyze amide hydrogen/deuterium exchange mass spectrometry (HDX-MS) data is proposed, utilizing a wider time window and isotope envelope analysis of each peptide. While most current scientific reports present HDX-MS data as a set of time-dependent deuteration levels of peptides, the ideal HDX-MS data presentation is a complete set of backbone amide hydrogen exchange rates. The ideal data set can provide single amide resolution, coverage of all exchange events, and the open/close ratio of each amide hydrogen in EX2 mechanism. Toward this goal, a typical HDX-MS protocol was modified in two aspects: measurement of a wider time window in HDX-MS experiments and deconvolution of isotope envelope of each peptide. Measurement of a wider time window enabled the observation of deuterium incorporation of most backbone amide hydrogens. Analysis of the isotope envelope instead of centroid value provides the deuterium distribution instead of the sum of deuteration levels in each peptide. A one-step, global-fitting algorithm optimized exchange rate and deuterium retention during the analysis of each amide hydrogen by fitting the deuterated isotope envelopes at all time points of all peptides in a region. Application of this strategy to cytochrome c yielded 97 out of 100 amide hydrogen exchange rates. A set of exchange rates determined by this approach is more appropriate for a patent or regulatory filing of a biopharmaceutical than a set of peptide deuteration levels obtained by a typical protocol. A wider time window of this method also eliminates false negatives in protein-ligand binding site identification. [ABSTRACT FROM AUTHOR]

Fourteen new sulphur-containing amides, glycocramides A-N (1–14), as well as nine known analogues (15–23) were isolated and characterized from Glycosmis craibii Tanaka. The chemical structures of new sulphur-containing amides 1–14 were ambiguously elucidated by extensive spectroscopic methods, while the known compounds 15–23 were identified by the comparison of their experimental spectral data with those described data in the literatures. The antiproliferative effects of all isolated sulphur-containing amides were evaluated in vitro. As a result, part of sulphur-containing amides showed remarkable inhibitory effects against MGC-803 cell line with IC 50 values ranging from 13.12 ± 0.10 to 20.03 ± 0.13 μM. These research results suggest that the sulphur-containing amides are potentially to be developed as a new natural anti-tumor drugs. [Display omitted] • Twenty-three sulphur-containing amides have been isolated and characterized from Glycosmis craibii Tanaka. • Fourteen new sulphur-containing amides, glycocramides A-N (1–14), were among them. • All of the isolated sulphur-containing amides represent two skeletons. • Antiproliferative effects of all isolated sulphur-containing amides were examined. [ABSTRACT FROM AUTHOR]

Fossil biomolecules from an endogenous source were previously identified in Cretaceous to Pleistocene fossilized bones, the evidence coming from molecular analyses. These findings, however, were called into question and an alternative hypothesis of the invasion of the bone by bacterial biofilm was proposed. Herewith we report a new finding of morphologically preserved blood-vessel-like structures enclosing organic molecules preserved in iron-oxide-mineralized vessel walls from the cortical region of nothosaurid and tanystropheid (aquatic and terrestrial diapsid reptiles) bones. These findings are from the Early/Middle Triassic boundary (Upper Roetian/Lowermost Muschelkalk) strata of Upper Silesia, Poland. Multiple spectroscopic analyses (FTIR, ToF-SIMS, and XPS) of the extracted "blood vessels" showed the presence of organic compounds, including fragments of various amino acids such as hydroxyproline and hydroxylysine as well as amides, that may suggest the presence of collagen protein residues. Because these amino acids are absent from most proteins other than collagen, we infer that the proteinaceous molecules may originate from endogenous collagen. The preservation of molecular signals of proteins within the "blood vessels" was most likely made possible through the process of early diagenetic iron oxide mineralization. This discovery provides the oldest evidence of in situ preservation of complex organic molecules in vertebrate remains in a marine environment. [ABSTRACT FROM AUTHOR]

Alkylacetamide-based model peptides display an intense Debye-type dielectric relaxation. In order to explore the extent to which this feature has to be regarded analogous to that in other supramolecular liquids, notably the monohydroxy alcohols, we applied broadband dielectric, time-dependent solvation, and near-infrared spectroscopies as well as shear rheology and various nuclear magnetic resonance techniques to mixtures of N-methylacetamide (NMA) or N-ethylacetamide (NEA) with N-methylformamide. Compared in the modulus format, dielectric relaxation, solvation dynamics, and mechanical response indicate a common global and local dynamics. The present spin-relaxation measurements reflect motional processes which are significantly faster than the dominant Debye dielectric response, and a similar conclusion is drawn from measurements of the shear viscosity. The NH overtone stretching vibrations reveal a temperature-dependent hydrogen-bond equilibrium that changes its characteristics near temperatures of 325 K. Finally, dielectric low-temperature data recorded for (NEA)0.4(NMF)0.6 mixed with 2-picoline indicate the existence of a critical concentration akin to the situation in various monohydroxy alcohol mixtures. [ABSTRACT FROM AUTHOR]

Spectroscopic Fourier self-deconvolution analysis was used to investigate β-sheet features in the secondary structure of hemoglobin under mobile phone microwaves at 900 MHz. To this end, four samples of hemoglobin in bidistilled water, sucrose, trehalose, and sodium chloride aqueous solutions were exposed for up to 4 hr to 900 MHz microwaves at an average H-field intensity of 42 mA/m. Quantitative spectral analyses highlighted significant increases in β-sheet contents in the Amide I region of hemoglobin samples in bidistilled water solution, but no appreciable change was observed in hemoglobin samples in sucrose, trehalose, and sodium chloride solutions. These results led us to conclude that mobile phone microwaves can denaturate hemoglobin in bidistilled water solution whereas sucrose, trehalose, and sodium chloride solutions produce a protective effect against microwaves, preserving the protein from unfolding. [ABSTRACT FROM AUTHOR]

As the systematic investigation of salicylatocopper complexes with nicotinamide derivatives the preparation, characterization and X-ray structure determination of four new molecular copper(II) complexes with x -methylsalicylate anion ( x -Mesal − ) and nicotinamide (nia) or N -methylnicotinamide (mna) are reported. The molecular complexes [Cu(5-Mesal) 2 (nia) 2 ] ( 1 ), [Cu(3-Mesal) 2 (nia) 2 ] ( 2 ) build up 2-D supramolecular structures of different character. The ladder-type supramolecular structure of ( 1 ) is formed by the head-to-head H-bonds of neighbouring carboxamide groups, while the supramolecular structure of ( 2 ) is formed by N H⋯O H-bonds of carboxamide groups into 1-D chain that are by the additional H H⋯O H-bonds of N H carboxamide and the carboxylate group oxygen atoms linked to 2-D layers. The centrosymmetrical crystal molecular structure of [Cu(4-Mesal) 2 (mna) 2 (H 2 O) 2 ]⋅2EtOH ( 3 ) or [Cu(5-Mesal) 2 (mna) 2 (H 2 O) 2 ]⋅2MeOH ( 4 ) are forming 1-D supramolecular chains that involve the methylcarboxamide N H group, the crystalosolvate alcohol O H group, the coordinated water molecule O H bond and oxygen atom of neighbouring complex molecule. The coordination polyhedron symmetry corresponds with the isotropic character of EPR spectra of ( 1 ) and ( 2 ) while the EPR spectrum of ( 4 ) is of axial symmetry. [ABSTRACT FROM AUTHOR]

Coprisamides A and B (1 and 2) were isolated from a bacterium in the gut of the dung beetle Copris tripartitus. Spectroscopic analysis revealed that the planar structures of 1 and 2 are novel cyclic heptapeptides bearing unusual units, such as β-methylaspartic acid and 2,3-diaminopropanoic acid branched to valine and 2-heptatrienyl cinnamic acid. Absolute configurations were established by chemical derivatization and chiroptical spectroscopy. The coprisamides displayed significant activity for induction of quinone reductase. [ABSTRACT FROM AUTHOR]

Four new isoquinoline alkaloids including a benzophenanthridine alkaloid (1), a morphine derivative (2), a narceine-type alkaloid (3) and a simple isoquinoline alkaloid (4), a new amide alkaloid (5) and a new phthalic acid derivative (6), together with eleven known alkaloids (7 – 17) were obtained from the whole herbs extract of Corydalis bungeana Turcz. Their structures and absolute configurations were elucidated by extensive spectroscopic data analysis including HRESIMS, NMR and electronic circular dichroism (ECD) and ECD calculation. Compounds 1 – 17 were evaluated for dopamine D2 receptor activity in CHO-D2 cells. Among them, 16 showed the highest antagonistic activity on the D2 receptor with an IC 50 value of 2.04 ± 0.01 μM. Compounds 14 and 15 exhibited moderate antagonism with IC 50 values of 13.66 ± 2.28 and 31.72 ± 2.52 μM, respectively. [Display omitted] • Five new alkaloids and a new phthalic acid derivative were obtained from Corydalis bungeana. • Their structures were evaluated by the analysis of extensive spectroscopic data. • Compound 16 exhibited significant antagonistic activity on dopamine D2 receptor in CHO-D2 cells. [ABSTRACT FROM AUTHOR]

A soil Streptomycesnov. sp. (MST-115088) isolatedfrom semiarid terrain near Wollogorang Station, Queensland, returnedtwo known and two new examples of a rare class of cyclic hexapeptide,desotamides A and B (1and 2) and E andF (3and 4), respectively, together withtwo new d-Orn homologues, wollamides A and B (5and 6). Structures were assigned by detailed spectroscopicand C3Marfey’s analysis. The desotamides/wollamidesexhibit growth inhibitory activity against Gram-positive bacteria(IC500.6–7 μM) and are noncytotoxic to mammaliancells (IC50>30 μM). The wollamides exhibit antimycobacterialactivity (IC502.8 and 3.1 μM), including reductionin the intracellular mycobacterial survival in murine bone marrow-derivedmacrophages. [ABSTRACT FROM AUTHOR]