Methyl Resonances Research Articles

Design and Synthesis of Novel Celecoxib Analogues with Potential Cytotoxic and Pro-apoptotic Activity against Breast Cancer Cell Line MCF-7.

Breast cancer is currently the leading cause of worldwide cancer incidence exceeding lung cancer. In addition, breast cancer accounts for 1 in 4 cancer cases and 1 in 6 cancer deaths among women. Cytotoxic chemotherapy is still the main therapeutic approach for patients with metastatic breast cancer. The aim of the study was to synthesize a series of novel celecoxib analogues to evaluate their anticancer activity against the MCF-7 cell line. Our design of target compounds was based on preserving the pyrazole moiety of celecoxib attached to two phenyl rings, one of them having a polar hydrogen bonding group (sulfonamide or methoxy group). The methyl group of the second phenyl ring was replaced with chlorine or bromine atom. Finally, the trifluoromethyl group was replaced with arylidene hydrazine-1-carbonyl moiety, which is substituted either with fluoro or methoxy group, offering various electronic and lipophilic environments. These modifications were carried out to investigate their effects on the antiproliferative activity of the newly synthesized celecoxib analogues and to provide a valuable structure- activity relationship. Four compounds, namely 4e-h, exhibited significant antitumor activity. Compounds 4e, 4f and 4h showed 1.2-2 folds more potent anticancer activity than celecoxib. Celecoxib analogue 4f showed the most potent anti-proliferative activity. Its anti-proliferative activity seems to associate well with its ability to inhibit BCL-2. Moreover, activation of the damage response pathway of the DNA leads to cell cycle arrest at the G2/M phase and accumulation of cells in the pre-G1 phase, indicating that cell death proceeds through an apoptotic mechanism. Compound 4f exhibited a potent pro-apoptotic effect via induction of the intrinsic mitochondrial pathway of apoptosis. This mechanistic pathway was proved by a significant increase in the expression of the tumor suppressor gene p53, elevation in Bax/BCL-2 ratio, and a significant increase in the level of active caspase-7. Furthermore, compound 4f showed moderate COX-2 inhibitory activity. Celecoxib analogue 4f is a promising multi-targeted lead for the design and synthesis of potent anticancer agents.

A comparative analysis of powder ENDOR spectra of aromatic and aliphatic radicals by exact and 1st order simulation

Exact and perturbation methods were employed in simulations of powder ENDOR spectra to obtain the anisotropic hyperfine ( hfc ) and nuclear quadrupole ( nqc ) coupling constants of certain organic radicals of interest in fundamental research and in applications in radiation research, surface chemistry and biophysics. The principal hfc values of the ring protons and methyl substituents for several aromatic cations trapped in disordered matrices might be more accurate than those previously reported using regular EPR. Only one of the earlier assignments of the naphthalene cation spectrum was in acceptable agreement with the simulations. The proton couplings at the β-position of alkyl radicals were deduced by simulations while the spectrum due to α-couplings with appreciable anisotropy was weak. Accurate simulation of the 14 N (I = 1) spectra in bio-radicals was obtained by adjustment of the relative orientation of the principal hfc and nuclear quadrupole coupling ( nqc ) tensors as well as the principal values. Adjustment of the excitation width parameter employed in the software was also required in a few cases to improve the agreement with the experimental spectra. The hfc patterns due to matrix nuclei ( 1 H and 7 Li) around the radicals of X-irradiated samples were simulated to elucidate the nature of the trapping sites in materials used for EPR dosimetry. ENDOR simulation programs known to us are presented in an Appendix. The performance of the ENDORF2 program used in previous works was examined by comparison with exact treatment. Input and output examples, source and executable codes used in this work can be downloaded at https://github.com/EndorF2/Simulation .

Production and optimization of bioplastic (Polyhydroxybutyrate) from Bacillus cereus strain SH-02 using response surface methodology

BackgroundPolyhydroxybutyrate (PHB) is a biopolymer formed by some microbes in response to excess carbon sources or essential nutrient depletion. PHBs are entirely biodegradable into CO2 and H2O under aerobic and anaerobic conditions. It has several applications in various fields such as medicine, pharmacy, agriculture, and food packaging due to its biocompatibility and nontoxicity nature.ResultIn the present study, PHB-producing bacterium was isolated from the Dirout channel at Assiut Governorate. This isolate was characterized phenotypically and genetically as Bacillus cereus SH-02 (OM992297). According to one-way ANOVA test, the maximum PHB content was observed after 72 h of incubation at 35 °C using glucose and peptone as carbon and nitrogen source. Response surface methodology (RSM) was used to study the interactive effects of glucose concentration, peptone concentration, and pH on PHB production. This result proved that all variables have a significant effect on PHB production either independently or in the interaction with each other. The optimized medium conditions with the constraint to maximize PHB content and concentration were 22.315 g/L glucose, and 15.625 g/L peptone at pH 7.048. The maximum PHB content and concentration were 3100.799 mg/L and 28.799% which was close to the actual value (3051 mg/l and 28.7%). The polymer was identified as PHB using FTIR, NMR, and mass spectrometry. FT-IR analysis showed a strong band at 1724 cm− 1 which attributed to the ester group’s carbonyl while NMR analysis has different peaks at 169.15, 67.6, 40.77, and 19.75 ppm that were corresponding to carbonyl, methine, methylene, and methyl resonance. Mass spectroscopy exhibited molecular weight for methyl 3- hydroxybutyric acid.ConclusionPHB–producing strain was identified as Bacillus cereus SH-02 (OM992297). Under optimum conditions from RSM analysis, the maximum PHB content and concentration of this strain can reach (3100.799 mg/L and 28.799%); respectively. FTIR, NMR, and Mass spectrometry were used to confirm the polymer as PHB. Our results demonstrated that optimization using RSM is one of the strategies used for reducing the production cost. RSM can determine the optimal factors to produce the polymer in a better way and in a larger quantity without consuming time.

An NMR look at an engineered PET depolymerase

Plastic environmental pollution is a major issue that our generation must face to protect our planet. Plastic recycling has the potential not only to reduce the pollution but also to limit the need for fossil-fuel-based production of new plastics. Enzymes capable of breaking down plastic could thereby support such a circular economy. Polyethylene terephthalate (PET) degrading enzymes have recently attracted considerable interest and have been subjected to intensive enzyme engineering to improve their characteristics. A quadruple mutant of Leaf-branch Compost Cutinase (LCC) was identified as a most efficient and promising enzyme. Here, we use NMR to follow the initial LCC enzyme through its different mutations that lead to its improved performance. We experimentally define the two calcium-binding sites and show their importance on the all-or-nothing thermal unfolding process, which occurs at a temperature of 72°C close to the PET glass transition temperature. Using various NMR probes such as backbone amide, methyl group, and histidine side-chain resonances, we probe the interaction of the enzymes with mono-(2-hydroxyethyl)terephthalic acid. The latter experiments are interpreted in terms of accessibility of the active site to the polymer chain.

Two methyl internal rotations of 2-acetyl-4-methylthiophene explored by microwave spectroscopy and quantum chemistry

The microwave spectrum of 2-acetyl-4-methylthiophene (2A4MT) was recorded in the frequency range from 2 to 26.5 GHz using a molecular jet Fourier transform microwave spectrometer, revealing two conformers, syn and anti. Both methyl groups in the molecule, the acetyl methyl and the ring methyl groups, undergo internal rotation, causing resolvable splittings of all rotational transitions into quintets. The torsional barriers determined for the acetyl methyl and the ring methyl rotors are 324.919(94) cm−1 and 210.7181(61) cm−1 for the syn conformer; the respective values for anti-2A4MT are 281.201(17) cm−1 and 212.9797(41) cm−1. The experimentally deduced rotational constants and torsional barriers are compared to values obtained from quantum chemical calculations. The barriers to methyl internal rotation are also compared to those of related molecules in order to establish a “thiophene class” concerning the acetyl methyl torsion.

NMR assignment of human HSP90 N-terminal domain bound to a long residence time resorcinol ligand.

HSP90 is a major molecular chaperone that helps both folding and stabilization of various client proteins often implicated in growth control and cell survival such as kinases and transcription factors. However, among HSP90 clients are also found numerous oncoproteins and, through its assistance to them, HSP90 has consequently been reported as a promising anticancer target. Several ligand chemotypes, including resorcinol type ligands, were found to inhibit HSP90, most of them in an ATP competitive manner. Binding of some of these ligands modify significantly the NMR spectrum of the HSP90 ATP binding domain compared to the apo protein spectrum, hampering assignment transfer from the previously assigned human HSP90 apo state. Here we report the assignment of the 1HN, 15N, 13C', 13Cα, 13Cβ, 1Hmethyl, and 13Cmethyl chemical shifts of the 29kDa HSP90 N-terminal domain bound to a long residence time resorcinol type inhibitor: 5-[4-(2-Fluoro-phenyl)-5-oxo-4,5-dihydro-1H-[1,2,4]triazol-3-yl]-N-furan-2-ylmethyl-2,4-dihydroxy-N-methyl-benzamide. 92% of the backbone resonances and 100% of the [1H, 13C]-resonances of Aβ, Mε, Tγ, Lδ2, Vγ2 and Iδ1 methyl groups were successfully assigned, including for the first time the assignment of the segment covering the nucleotide/drug binding site. Secondary structure predictions based on the NMR assignment reveal a structural rearrangement of HSP90 N-terminal domain upon ligand binding. The long residence time ligand induces the formation of a continuous helix covering the ligand binding site of HSP90 N-terminal domain accounting for the large differences observed in the NMR spectra between the apo and bound proteins.

Systematically Exploring the Chemical Ingredients and Absorbed Constituents of Polygonum capitatum in Hyperuricemia Rat Plasma Using UHPLC-Q-Orbitrap HRMS.

Polygonum capitatum as an ethnic medicine has been used to treat urinary tract infections, pyelonephritis and urinary calculi. In our previous study, P. capitatum was found to have anti-hyperuricemia effects. Nevertheless, the active constituents of P. capitatum for treating hyperuricemia were still unclear. In this study, an ultra-high-performance liquid chromatography coupled to quadrupole/orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) was used to comprehensively detect the chemical ingredients of P. capitatum and its absorbed constituents in the plasma of hyperuricemia rats for the first time. Xcalibur 3.0 and Compound Discoverer 2.0 software coupled to mzCloud and ChemSpider databases were utilized for qualitative analysis. A total of 114 chemical components including phenolics, flavonoids, tannins, phenylpropanoids, amino acids, amides and others were identified or tentatively characterized based on the exact mass, retention time and structural information. Compared to the previous P. capitatum study, an additional 66 different components were detected. Moreover, 68 related xenobiotics including 16 prototype components and 52 metabolites were found in the plasma of hyperuricemia rats. The metabolic pathways included ring fission, hydrolysis, decarboxylation, dehydroxylation, methylation, glucuronidation and sulfation. This work may provide important information for further investigation on the active constituents of P. capitatum and their action mechanisms for anti-hyperuricemia effects.

C-methylation of Organic Substrates: A Comprehensive Overview; Methanol as a Methylating Agent: A Case of Catalysis Versatility (Part III)#

Abstract: The present account surveys the results of a myriad of works on the C-methylation of organic substrates with methanol as an eco-friendly methylating agent. The innumerable reports on this issue reveal the widespread use of a set of solid catalysts such as molecular sieves, zeolites, metal phosphates, metal oxides and transition metal complexes to accomplish such methylation. One related facet was the impact of the numbers of Brønstëd acid sites, Lewis acid sites, and Lewis base sites present in solid catalysts, such as zeolites, their ratios, and strengths that affect the distribution of the methylation products and their selectivities. Moreover, specific surface area and porosity of some solid catalysts, such as zeolites, play additional roles in the overall reaction. Not only do these catalyst properties influence the methylation outcome, the temperature, space velocity (WHSV, LHSV, GSHV), weight of catalyst per reactant flow rate (W/F), time of stream (TOS), and methanol/ substrate molar ratio also do. The treated substrates herein discussed were aromatic hydrocarbons (benzene, biphenyls, naphthalenes, toluene, xylenes), alkenes, phenolics (phenol, cresols, anisole), Nheteroarenes, carbonyls, alcohols, and nitriles. Methylation of benzene affords not only toluene as the main product but also polymethylated benzenes (xylenes, pseudocumene, hexamethylenebenzene, and also ethylbenzene as a side-chain product). Furthermore, toluene is sensitive to the reaction conditions, giving rise to ring methylation and to side-chain one (ethylbenzene and styrene), besides the formation of benzene as a disproportionation product. A number of results from the methylation of phenolic compounds bear witness to the interest of different investigators in this special research. With respect to these phenolics, concurrent O-methylation inevitably parallels the C-methylation, and the selectivity of the latter one remains dependent on the above-cited factors; ortho-cresol and 2,6-xylenol have been the main C-ring methylated phenols. Methylation of olefins with methanol over solid catalysts, leading to higher olefins, is of great interest. The chemistry involved in the methylation of N-heteroarenes, such as pyridines, indoles, and pyrroles, is significant. Application of the methylation protocols, using methanol as a reagent and transition of metal complexes as catalysts to ketones, esters, aldehydes, nitriles, and alcohols, ends up with some important molecules, such as acrylonitrile (a monomer) and isobutanol (a biofuel).

Internal dynamics of methyl p-tolyl sulfoxide in the gas phase: Rotational spectroscopy and theoretical studies.

A pure rotational spectrum of methyl p-tolyl sulfoxide (MTSO) was studied using chirped-pulse Fourier transform microwave spectroscopy in the frequency range of 18-26GHz. A single conformer was unambiguously observed in the supersonic jet expansion, which is consistent with the conformational analysis performed using quantum-chemical calculations. Rotational transitions were split into two components of A and E symmetries due to the low-barrier internal rotation of the ring methyl group [V3 = 11.0178(23) cm-1]. The low energy barrier for the methyl top internal rotation implies an electron-withdrawing effect of the group at the opposite side of the phenyl ring, in comparison with other para-substituted toluenes. The effective ground state (r0) geometry was derived using the rotational constants from the parent species and the 34S and eight 13C singly substituted isotopologues. Compared to two other sulfoxides, methyl phenyl sulfoxide and methyl 4-nitrophenyl sulfoxide, the sulfoxide group in MTSO is slightly more twisted with respect to the plane of the phenyl ring, which could be attributed to the moderate electron-donating effect of the p-methyl group. Furthermore, the pyramidal inversion that interconverts the handedness at the sulfur stereogenic center was explored in the electronic ground (S0) and excited (S1) states with nudged elastic band and time-dependent density functional theory methods. It was found that the pyramidal inversion in S1 is easier than in S0, showing that optical excitation to S1 will facilitate an effectively barrier-free inversion.

NMR Assignment of Methyl Groups in Immobilized Proteins Using Multiple-Bond 13C Homonuclear Transfers, Proton Detection, and Very Fast MAS.

In nuclear magnetic resonance spectroscopy of proteins, methyl protons play a particular role as extremely sensitive reporters on dynamics, allosteric effects, and protein–protein interactions, accessible even in high-molecular-weight systems approaching 1 MDa. The notorious issue of their chemical shift assignment is addressed here by a joint use of solid-state 1H-detected methods at very fast (nearly 100 kHz) magic-angle spinning, partial deuteration, and high-magnetic fields. The suitability of a series of RF schemes is evaluated for the efficient coherence transfer across entire 13C side chains of methyl-containing residues, which is key for establishing connection between methyl and backbone 1H resonances. The performance of ten methods for recoupling of either isotropic 13C–13C scalar or anisotropic dipolar interactions (five variants of TOBSY, FLOPSY, DIPSI, WALTZ, RFDR, and DREAM) is evaluated experimentally at two state-of-the-art magic-angle spinning (55 and 94.5 kHz) and static magnetic field conditions (18.8 and 23.5 T). Model isotopically labeled compounds (alanine and Met-Leu-Phe tripeptide) and ILV-methyl and amide-selectively protonated, and otherwise deuterated chicken α-spectrin SH3 protein are used as convenient reference systems. Spin dynamics simulations in SIMPSON are performed to determine optimal parameters of these RF schemes, up to recently experimentally attained spinning frequencies (200 kHz) and B 0 field strengths (28.2 T). The concept of linearization of 13C side chain by appropriate isotope labeling is revisited and showed to significantly increase sensitivity of methyl-to-backbone correlations. A resolution enhancement provided by 4D spectroscopy with non-uniform (sparse) sampling is demonstrated to remove ambiguities in simultaneous resonance assignment of methyl proton and carbon chemical shifts.

Understanding the Solvation-Dependent Properties of Cyclic Ether Multivalent Electrolytes Using High-Field NMR and Quantum Chemistry.

Efforts to expand the technological capability of batteries have generated increased interest in divalent cationic systems. Electrolytes used for these electrochemical applications often incorporate cyclic ethers as electrolyte solvents; however, the detailed solvation environments within such systems are not well-understood. To foster insights into the solvation structures of such electrolytes, Ca(TFSI)2 and Zn(TFSI)2 dissolved in tetrahydrofuran (THF) and 2-methyl-tetrahydrofuran were investigated through multi-nuclear magnetic resonance spectroscopy (17O, 43Ca, and 67Zn NMR) combined with quantum chemistry modeling of NMR chemical shifts. NMR provides spectroscopic fingerprints that readily couple with quantum chemistry to identify a set of most probable solvation structures based on the best agreement between the theoretically predicted and experimentally measured values of chemical shifts. The multi-nuclear approach significantly enhances confidence that the correct solvation structures are identified due to the required simultaneous agreement between theory and experiment for multiple nuclear spins. Furthermore, quantum chemistry modeling provides a comparison of the solvation cluster formation energetics, allowing further refinement of the preferred solvation structures. It is shown that a range of solvation structures coexist in most of these electrolytes, with significant molecular motion and dynamic exchange among the structures. This level of solvation diversity correlates with the solubility of the electrolyte, with Zn(TFSI)2/THF exhibiting the lowest degree of each. Comparisons of analogous Ca2+ and Zn2+ solvation structures reveal a significant cation size effect that is manifested in significantly reduced cation–solvent bond lengths and thus stronger solvent bonding for Zn2+ relative to Ca2+. The strength of this bonding is further reduced by methylation of the cyclic ether ring. Solvation shells containing anions are energetically preferred in all the studied electrolytes, leading to significant quantities of contact ion pairs and consequently neutrally charged clusters. It is likely that the transport and interfacial de-solvation/re-solvation properties of these electrolytes are directed by these anion interactions. These insights into the detailed solvation structures, cation size, and solvent effects, including the molecular dynamics, are fundamentally important for the rational design of electrolytes in multivalent battery electrolyte systems.

1H, 13C and 15N resonance assignment of backbone and IVL-methyl side chain of the S135A mutant NS3pro/NS2B protein of Dengue II virus reveals unique secondary structure features in solution

The serotype II Dengue (DENV 2) virus is the most prevalent of all four known serotypes. Herein, we present nearly complete 1H, 15N, and 13C backbone and 1H, 13C isoleucine, valine, and leucine methyl resonance assignment of the apo S135A catalytically inactive variant of the DENV 2 protease enzyme folded as a tandem formed between the serine protease domain NS3pro and the cofactor NS2B, as well as the secondary structure prediction of this complex based on the assigned chemical shifts using the TALOS-N software. Our results provide a solid ground for future elucidation of the structure and dynamic of the apo NS3pro/NS2B complex, key for adequate development of inhibitors, and a thorough molecular understanding of their function(s).

CFD simulation of a swirling vortex cavitator and its degradation performance and pathway of tetracycline in aqueous solution

Abstract The vortex cavitation technology shows a great development potential for antibiotic wastewater treatment. We have designed a novel swirling vortex cavitator for tetracycline degradation in aqueous solution. By Computational Fluid Dynamics (CFD) simulation using ANSYS CFX flow field calculation software, it was found that the vortex cavitator could form a low-pressure area far lower than the saturated vapor pressure at experimental temperature, resulting in generation of obvious vortex cavitation effect, which also proved by the concentration of hydroxyl radical of 4.58 μmol/L measured by methylene blue method. Moreover, the tetracycline degradation process may be mainly caused by the oxidation of hydroxyl radicals. The batch experiments results showed when the degradation time was 30 min, the vortex cavitator had a good degradation ability of tetracycline in pH range of 5.0–9.0. The degradation efficiency of 2.0 mg/L tetracycline solution was 76.45% within 50 min at pH 7.0. The possible intermediate products of tetracycline were determined by HPLC-MS Spectrometry. A series of reactions including hydroxylation, decarbonylation and C–N bond cleavage, ring-opening, and removing two methyl groups in the carbon atom ring, occur during the degradation.

Stability and Self-Association of styryl hemicyanine dyes in water studied by 1H NMR spectroscopy

The stability in water of five styryl hemicyanine dyes containing benzoxazole, benzothiazole, benzoselenazole and oxazolopyridne rings with different substituents at different pH values has been investigated. All compounds are stable at acidic and neutral pH, however, at basic pH the oxazole dyes undergo a ring opening reaction. The stability at basic pH is increased by substituting the benzooxazolium with oxazolopyridium function in the oxazole dyes 3a and 3e. 1H and 1H DOSY solution NMR spectroscopy prove that slight structural changes result in significant differences in the process of self-association. The association constants for dimerization have been determined by curve fitting the concentration dependent 1H NMR spectra based on the isodesmic model. Van’t Hoff analysis has been used to determine the thermodynamic parameters of the self-association process. The aggregation in water decreases with decreasing electronegativity and increasing the charge delocalization in the row (E)-2-(4-(dimethylamino)styryl)-3-methylbenzo[d]oxazol-3-ium iodide (3a), (E)-2-(4-(dimethylamino)styryl)-3-methylbenzo[d]thiazol-3-ium iodide (3b), (E)-2-(4-(dimethylamino)styryl)-3-methylbenzo[1,3-d]selenazol-3-ium iodide (3d) in the oxazole/thiazole/selenazole analogues. Introducing methyl groups in the benzothiazole ring enhances stacking effects in water due to stronger hydrophobic character. This derivative is characterized by the highest self-association constant (ka = 299 L mol−1) and the lowest Gibbs energy (ΔG = -14 kJ mol−1). Substituting the phenyl with pyridyl ring in the oxazole analogue enhances significantly the solubility in water and thus decreases the self-association constant. Concentration dependent 1H ROESY spectra provide information about the orientation of the molecules in the stack.

Assignment of Ala, Ile, LeuproS, Met, and ValproS methyl groups of the protruding domain of murine norovirus capsid protein VP1 using methyl–methyl NOEs, site directed mutagenesis, and pseudocontact shifts

The protruding domain (P-domain) of the murine norovirus (MNV) capsid protein VP1 is essential for infection. It mediates receptor binding and attachment of neutralizing antibodies. Protein NMR studies into interactions of the P-domain with ligands will yield insights not easily available from other biophysical techniques and will extend our understanding of MNV attachment to host cells. Such studies require at least partial NMR assignments. Here, we describe the assignment of about 70% of the Ala, Ile, LeuproS, Met, and ValproS methyl groups. An unfavorable distribution of methyl group resonance signals prevents complete assignment based exclusively on 4D HMQC-NOESY-HMQC experiments, yielding assignment of only 55 out of 100 methyl groups. Therefore, we created point mutants and measured pseudo contact shifts, extending and validating assignments based on methyl-methyl NOEs. Of note, the P-domains are present in two different forms caused by an approximate equal distribution of trans- and cis-configured proline residues in position 361.

Kinetics and mechanism of sequential ring methyl C-H activation in cyclopentadienyl rhodium(III) complexes.

We have studied activation of the methyl C-H bonds in the cyclopentadienyl ligands of half-sandwich Rh(III) complexes [η5-CpXRh(N,N')Cl]+ by observing the dependence of sequential H/D exchange on variations in CpX = Cp* (complexes 1 and 2), Me4PhCp (CpXPh, 3) or Me4PhPhCp (CpXPhPh, 4), and chelated ligand N,N' (bpy, 1; phen, 2-4). H/D exchange was fastest in d4-MeOD (t1/2 = 10 min, 37 °C, complex 1), no H/D exchange was observed in DMSO/D2O, and d4-MeOD enhanced the rate in CD3CN. The proposed Rh(I)-fulvene intermediate was trapped by [4 + 2] Diels-Alder reactions with conjugated dienes and characterized. The Rh(I) oxidation state was confirmed by X-ray photoelectron spectroscopy (XPS). Influence of solvent on the mechanisms of activation and Diels-Alder adduct formation was modelled using DFT calculations with the CAM-B3LYP functional and CEP-31 g basis set, and influence on the reaction profile of the dimiine ligand and phenyl substituent using the larger qzvp basis set. The Rh(III)-OH intemediate is stabilised by H-bonding with methanol and a Cp* CH3 hydrogen. The Rh(I)(Me4fulvene) species, stabilised by interaction of methanol with a coordinated water, again by two H-bonds H2O-HOMe (1.49 Å) and fulvene CH2 (1.94 Å), arises from synchronous transfer of the methanol OH proton to a Rh(III)-OH ligand and Cp* methyl hydrogen to the methanol oxygen. Additionally, the observed trend in catalytic activity for complexes 1-4 was reproduced by DFT calculations. These complexes form a novel class of catalytic molecular motors with a tunable rate of operation that can be stalled in a given state. They provide a basis for elucidation of the effects of ligand design on the contributions of electronic, rotational and vibrational energies to each step in the reaction pathway at the atomic level, consideration of which will enhance the design principles for the next generation of molecular machines.

γ-Agostic interactions in (MesCCC)Fe-Mes(L) complexes.

Agostic interactions were observed in the bound mesityl group in a series of iron compounds bearing a bis(NHC) pincer CCC ligand. The L-type ligand on [(CCC)FeIIMes(L)] complexes influences the strength of the agostic interaction and is manifested in the upfield shift of the 1H NMR resonance for the mesityl methyl resonances. The nature of the interaction was further investigated by density functional theory calculations, allowing rationalization of some unexpected trends and proving to be a powerful predictive tool.

Fat unsaturation measures in tibial, subcutaneous and breast adipose tissue using short and long TE MRS at 3 T

Fat unsaturation and poly-unsaturation measures can be obtained in vivo with magnetic resonance spectroscopy (MRS) through the olefinic (≈5.4 ppm) and diallylic (≈2.8 ppm) resonances, respectively. Long echo time (TE) MRS sequences have been previously optimized for olefinic/methylene (≈1.3 ppm) or olefinic/methyl (≈0.9 ppm) measures. The objectives of this work, using a Point RESolved Spectroscopy (PRESS) sequence, are to: 1) Investigate olefinic, methyl and methylene resonance decay in subcutaneous, tibial, and breast adipose tissue to determine if a direct comparison of unsaturation measures can be made without correction for T2 losses. 2) Assess intra-individual fat unsaturation and poly-unsaturation measures in the three adipose tissues. 3) Estimate correction factors for olefinic to methylene ratios to compensate for J-coupling and T2 relaxation losses that take place when increasing PRESS TE from 40 ms to 200 ms (previously optimized long-TE). 4) Investigate the utility of an inversion recovery for resolving the olefinic resonance from water in adipose tissue.PRESS spectra were acquired from the three adipose regions (breast in female only) in healthy volunteers at 3 T. It was found that olefinic and methyl signal decays faster in breast tissue compared to in tibial bone marrow. Poly-unsaturation measures (diallylic/methylene) differ for tibial bone marrow compared to subcutaneous and breast adipose tissue, with average values of 1.7 ± 0.4, 2.2 ± 0.4, and 2.3 ± 0.8%, respectively. PRESS (TE = 40 ms) with an inversion recovery resolves the olefinic and water resonances in breast tissue with a signal to noise ratio approximately six times greater than that using PRESS with a TE of 200 ms. Stimulated Echo Acquisition Mode (STEAM) with a TE of 20 ms (mixing time of 20 ms) was also combined with IR to resolve the olefinic resonance from that of water is spinal bone marrow.

Backbone and Ile, Leu, Val methyl group resonance assignment of CoV-Y domain of SARS-CoV-2 non-structural protein 3.

The worldwide COVID-19 pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Nonstructural protein 3 (nsp3) has 1945 residues and is the largest protein encoded by SARS-CoV-2. It comprises more than a dozen independent domains with various functions. Many of these domains were studied in the closely-related virus SARS-CoV following an earlier outbreak. Nonetheless structural and functional information on the C-terminal region of nsp3 containing two transmembrane and three extra-membrane domains remains incomplete. This part of the protein appears to be involved in initiation of double membrane vesicle (DMV) formation, membranous organelles the virus builds to hide its replication-transcription complex from host immune defenses. Here we present the near-complete backbone and Ile, Leu, and Val methyl group chemical shift assignments of the most C-terminal domain of nsp3, CoV-Y. As the exact function and binding partners of CoV-Y remain unknown, our data provide a basis for future NMR studies of protein–protein interactions to elucidate the molecular mechanism of DMV formation.

SYNTHESIS, CHARACTERIZATION AND PROPERTIES OF PROCESSABLE POLYAZOMETHINES FOR HIGH TEMPERATURE APPLICATIONS

New dithiazole-diamine monomer containing cyclohexylidene ring and pendant methyl group i.e. 1,1-bis [4-(2- aminothiazole)-3-methyl phenyl] cyclohexane (BATMPC) was synthesized through various steps. The structure of new dithiazole amine monomer was confirmed by FT-IR, 1H NMR and 13CNMR Spectrometry. A series of polyazomethines containing cardo cyclohexane-thiazole unit have been incorporated by the polycondensation of a new diamine i.e. (BATMPC), with proportionate of aromatic dialdehydes. The impact of insertion of cardo cyclohexane, pendant methyl group and thiazole entity in the polyazomethine matrix with the dialdehydes [isophthalaldehyde (1,3 IPA) and terephthalaldehyde (1,4 TPA)], on solubility and thermal stability has been studied. All polyazomethines shown Tg in the range of 220-241ºC and T10% value of all thermally stable polyazomethines in nitrogen atmosphere was in between of 395-415ºC These polyazomethines exhibited solubility in various polar aprotic solvents such as NMP, DMSO, DMAc, DMF etc. However, these polyazomethines were insoluble in common solvents such as DCM and CHCl3. X-ray diffraction study confirms that all the polyazomethines are amorphous in nature having broad peak in the range of 2θ=20°. The UV absorption at 360 nm shows that there is a formation of imine (-C=N-) linkages in the polymer matrix which is helpful for the conduction of electron throughout. The structure-property correlation among these polyazomethines was studied, in view of their potential applications for high temperature applications.