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The prebiotic origin of catalyst-controlled peptide synthesis is fundamental to understanding the emergence of life. Building on our recent discovery that thiols catalyze the ligation of amino acids, amides, and peptides with amidonitriles in neutral water, we demonstrate the outcome of ligation depends on pH and that high pKaprimary thiols are the ideal catalysts. While the most rapid thiol catalyzed peptide ligation occurs at pH 8.5–9, the most selective peptide ligation, that tolerates all proteinogenic side chains, occurs at pH 7. We have also identified the highly selective mechanism by which the intermediate peptidyl amidines undergo hydrolysis to α-peptides while demonstrating that the hydrolysis of amidines with nonproteinogenic structures, such as β- and γ-peptides, displays poor selectivity. Notably, this discovery enables the highly α-selective protecting-group-free ligation of lysine peptides at neutral pH while leaving the functional ε-amine side chain intact.

Graphite microparticles were oxidized to graphene oxide (MPGO) by Hummers’ method followed by thermal exfoliation (C/O ratio 1.53). Graphene oxide was modified with SO2(mMPGO) at 600 °C and by subsequent treatment at 200 °C having a sulfur content of 10.9% (C/O ratio 16.94) and manganese content 9.39 μmol·g–1. The XPS spectrum of MPGO showed the presence of carbonyl and epoxide groups. The reactivity of mMPGO toward alkyl thiol and alkyl amine showed the same selectivity as other carbons and suggested that oxidation did not modify deeply the edging structure of graphite. Therefore, the tetradehydrogenated-benzo[α]anthracene (TBA) reactive site model is valid. From XPS and solid-state NMR, amino-thiolysis occurred via cyclization. On the basis of the joint analysis of solid-state 1H and 13C NMR spectra of mMPGOs treated with mono- and difunctionalized alkanes, a preferred conformation of the alicyclic moiety of aminothiol over the graphene matrix occurred via binding to mMPGO at both amine and thiol ends. It was found that paramagnetic manganese ions in mMPGO can lead to cross-polarization inefficiency in the 13C CPMAS detection of alkyl chains bound to mMPGO, while ring currents from graphene aromatic layers can shift alkyl 1H NMR signals to lower frequencies by up to 4 ppm.

Four new conjugated microporous polymers (CMPs) were synthesized by a Buchwald–Hartwig (BH) cross-coupling reaction of tri- and tetrafunctionalized precursors to yield materials with tunable surface area and pore size distribution. This approach yielded LPCMP1–4, CMPs with significantly higher Brunauer–Emmett–Teller (BET) surface areas (more than 5 times higher) than other related BH-based CMPs. These CMPs possess not only high BET specific surface areas and high chemical and thermal stabilities, but also exhibit outstanding swellability. To the best of our knowledge, swellable behavior was studied in great detail for CMPs for the first time, with the greatest degree of swelling for methanol reaching 16.5 and 16.3 mL g–1for LPCMP1and LPCMP3, respectively. Owing to their excellent swellability, we further studied the adsorption capacity of these CMPs for different toxic organic vapors (including toluene and methanol). LPCMP1and LPCMP3adsorbed 124 and 117 mg g–1toluene, respectively, at saturated vapor pressure. For methanol, the adsorption capacities of LPCMP1and LPCMP3were up to 250 and 215 mg g–1, respectively, which are the highest recorded values when compared with published data for CMPs, HCPs, MOFs, and porous carbons. These materials are promising candidates for the removal and elimination of hazardous organic vapors and chemical warfare agents. Moreover, all the polymers show high sensitivity to nitroaromatic explosives. LPCMP2and LPCMP4exhibit high selectivity for TNT and may be suitable as new candidates to selectively detect TNT for security or environmental applications.

The Pd-mediated oxidation of unsaturated thioacetals gives either allyl or vinyl esters, depending on the substrate structure. We report the characterization of a range of sulfur-stabilized palladium intermediates via a combined computational and experimental NMR approach, demonstrating that the oxidation proceeds via two divergent reaction mechanisms. We were also able to synthesize an unusual σ-bound Pd complex, via acetoxypalladation of an unsaturated dithiane, which was characterized by X-ray crystallography.

A comparison of chlorido-gallium functionalized alkoxides as precursors for aerosol-assisted chemical vapor deposition (AACVD) was carried out. Variable-temperature (VT)-NMR studies were used to probe the fluxional behavior of these alkoxides in solution, and hence their utility as precursors. The synthesis involved the initial isolation of the dimer [GaCl(NMe2)2]2via a salt metathesis route from GaCl3and 2 equiv of LiNMe2. This dimer was then reacted with 4 equiv of HOCH2CH2CH2NEt2, resulting in the formation of Ga[μ-(OCH2CH2CH2NEt2)2GaCl2]3(1). Mass spectrometry and VT-NMR confirmed the oligomeric structure of 1. Tuning of the ligand properties, namely, the chain length and substituents on N, resulted in formation of the monomers [GaCl(OR)2] (R = CH2CH2NEt2, (2); CH2CH2CH2NMe2, (3)). VT-NMR studies, supported by density functional theory calculations, confirmed that the ligands in both 2and 3possess a hemilabile coordination to the gallium center, owing to either a shorter carbon backbone (2) or less steric hindrance (3). Both 2and 3were selected for use as precursors for AACVD: deposition at 450 °C gave thin films of amorphous Ga2O3, which were subsequently annealed at 1000 °C to afford crystalline Ga2O3material. The films were fully characterized by X-ray diffraction, X-ray photoelectron spectroscopy, scanning electron microscopy, UV–visible spectroscopy, and energy dispersive X-ray analysis.

Temperature-controlled, solvent-free centrifugal spinning may be used as a means of rapid production of amorphous solid dispersions in the form of drug-loaded sucrose microfibers. However, due to the high content of amorphous sucrose in the formulations, such microfibers may be highly hygroscopic and unstable on storage. In this study, we explore both the effects of water uptake of the microfibers and the consequences of deliberate recrystallization for the associated dissolution profiles. The stability of sucrose microfibers loaded with three selected BCS class II model drugs (itraconazole (ITZ), olanzapine (OLZ), and piroxicam (PRX)) was investigated under four different relative humidity conditions (11, 33, 53, and 75% RH) at 25 °C for 8 months, particularly focusing on the effect of the highest level of moisture (75% RH) on the morphology, size, drug distribution, physical state, and dissolution performance of microfibers. While all samples were stable at 11% RH, at 33% RH the ITZ–sucrose system showed greater resistance against devitrification compared to the OLZ– and PRX–sucrose systems. For all three samples, the freshly prepared microfibers showed enhanced dissolution and supersaturation compared to the drug alone and physical mixes; surprisingly, the dissolution advantage was largely maintained or even enhanced (in the case of ITZ) following the moisture-induced recrystallization under 75% RH. Therefore, this study suggests that the moisture-induced recrystallization process may result in considerable dissolution enhancement compared to the drug alone, while overcoming the physical stability risks associated with the amorphous state.

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p‐Nitrobenzyl amylose xanthate (AmXNB) was synthesized and characterized by 13C NMR spectroscopy in solution and the solid state. The degree of substitution (DS), calculated from the sulfur content, was 7.0, and this value was similar to that obtained from solid‐state 13C NMR using the signal of C‐1 as internal standard. The hydrolysis of AmXNB was studied in 10% (v/v) DMSO with µ = 0.5 (KCl) at 25 °C. The basic hydrolysis was pseudo‐first order, but the water‐catalyzed hydrolysis in the pH range 7–9 showed a biphasic plot of ln (ΔAbsorbance) vs time, as has been observed for cellulose xanthate esters, occurring through two parallel reactions with rate constants k′H2O(fast) = 5.3 × 10−5s−1and k″H2O(slow) = 3.3 × 10−6s−1. The fast hydrolysis was more than three orders of magnitude faster than that of the O‐ethyl analog. The activation parameters were ΔH≠= 20.5 kcal mol−1and ΔS≠= +10 cal K−1mol−1. They showed that the acceleration of the fast hydrolysis of AmXNB and cellulose analogs is due to an entropy of activation effect. There is a linear increase of logk′H2O(fast) with increase in the concentration of the small Li+ion that produces an increase of the 3‐D hydrogen‐bond network of water while the large singly charged iodide ion has a considerable inverse effect. These results are strongly consistent with the theory that the supramolecular catalysis induced by modified polysaccharide esters is due to the 3‐D hydrogen‐bond network of the water in the solvation shell. Copyright © 2003 John Wiley & Sons, Ltd.

p-Nitrobenzyl amylose xanthate (AmXNB) was synthesized and characterized by ¹³C NMR spectroscopy in solution and the solid state. The degree of substitution (DS), calculated from the sulfur content, was 7.0, and this value was similar to that obtained from solid-state ¹³C NMR using the signal of C-1 as internal standard. The hydrolysis of AmXNB was studied in 10% (v/v) DMSO with µ = 0.5 (KCl) at 25 °C. The basic hydrolysis was pseudo-first order, but the water-catalyzed hydrolysis in the pH range 7–9 showed a biphasic plot of ln (ΔAbsorbance) vs time, as has been observed for cellulose xanthate esters, occurring through two parallel reactions with rate constants k'H2O (fast) = 5.3 × 10⁻⁵ s⁻¹ and k"H2O (slow) = 3.3 × 10⁻⁶ s⁻¹. The fast hydrolysis was more than three orders of magnitude faster than that of the O-ethyl analog. The activation parameters were ΔH^≠ = 20.5 kcal mol⁻¹ and ΔS^≠ = +10 cal K⁻¹ mol⁻¹. They showed that the acceleration of the fast hydrolysis of AmXNB and cellulose analogs is due to an entropy of activation effect. There is a linear increase of logk'H2O (fast) with increase in the concentration of the small Li⁺ ion that produces an increase of the 3-D hydrogen-bond network of water while the large singly charged iodide ion has a considerable inverse effect. These results are strongly consistent with the theory that the supramolecular catalysis induced by modified polysaccharide esters is due to the 3-D hydrogen-bond network of the water in the solvation shell. Copyright © 2003 John Wiley & Sons, Ltd.

A binding site optimisation protocol for the design of artificial enzymes based on “small molecule–small molecule” binding studies by diffusion NMR is presented. Since the reaction chosen was the hydrolysis of ester 1 ([4-(4-carboxy-1-oxobutyl)-aminobenzyl]-phenethyl ester), an analogous phosphonate ester 2 ([4-(4-carboxy-1-oxobutyl)-aminobenzyl]-phosphonic phenethyl ester) was selected as a suitable transition state analogue (TSA). The key objective of the NMR studies was to find a unit with functional groups capable of binding to the acidic sites of the TSA. Nine dipeptides, mainly with basic and hydroxyl groups, were used and their affinity to the TSA was studied by measuring the change in the diffusion coefficient, Dpep, upon binding by pulse field gradient NMR. The value of Dpep at 298 K in D2O at pD 5, 7 and 10 was measured both in free solution, and mixtures containing one dipeptide and the TSA. As both components are low molecular weight species with M < 500, a TSA-to-dipeptide ratio of 10:1 was used to detect significant changes in Dpep. The results revealed that dipeptides with basic residues show higher affinity to the TSA than those with hydroxyl or aliphatic side chains in aqueous solutions. The dipeptide showing the most significant relative change in Dpep was H-Arg-Arg-OH, and the binding constant was estimated to be 86 L M⁻¹ by measuring Dpep at varying concentrations of the TSA. In addition, binding of the TSA to a new water-soluble polymer with a polyallylamine backbone and randomly distributed Arg-Arg binding sites was examined, and the binding constant was estimated to be ≥1500 L M⁻¹. As confirmed by further catalytic activity tests, polymers containing Arg-Arg as a binding site are capable of significant rate accelerations in the hydrolysis of ester 1.

Potassium chitosan dithiocarbamate (ChitDTC) was synthesized and characterized by elemental analysis and solid-state ¹³C NMR spectroscopy. The degree of substitution (DS) (number of substituents per 100 2-amino-2-deoxyglucopyranoside units) and molalities of the groups were calculated for acetylamino, amino and dithiocarbamate substituents in chitin, chitosan and ChitDTC. A comparative study of the retention and exchange of Cu(II) was performed with chitin, chitosan and ChitDTC at 30 °C, pH 6.0 (0.1 M succinate). The stability constants, KX, for the heterogenous equilibrium $\hbox{ChitX} + \hbox{Cu(II)}\ {\buildrel K_{\rm X} \over \rightleftharpoons}\ \hbox{ChitXCu(II)}$ were calculated assuming that complexing of Cu(II) ions was largely in a 1:1 ratio with respect to each group. The values of KX for each group were NHAc 45.1, DTC 3.14 × 10³, and NH2 1.12 × 10⁴. It is proposed that in the presence of succinate, the main species of aqua Cu(II) ion present in solution must be the uncharged Cu(II)–succinate complex that prevents the acetylamino, amino and DTC groups from forming complexes higher than 1:1. Also, this may explain the fact that the stability constant for DTC was lower than for the amino group. The method allows the characterization of the chelating ability of each group in ChitDTC with respect to metal ions. Copyright © 2002 John Wiley & Sons, Ltd.

The title compound was studied by dynamic NMR spectroscopy in solution and in the solid state, and by MM3 molecular mechanics calculations of model compounds. Barriers to rotation of the trimethyltin group, the tricarbonylchromium group, the triisopropylsilyl group, and the isopropyl groups were all too small to measure by NMR in solution i.e. less than about 5 kcal/mol. All of these barriers could be measured, however, in the solid state, are of different sizes, and are surprisingly large, up to 12.9 kcal/mol. A crystal structure determination shows close intermolecular interactions of these triple rotors that explain these high rotation barriers.

The thermally induced solid‐state polymerization reactions in sodium chloroacetate and sodium bromoacetate, leading to poly(hydroxyacetic acid) (polyglycolide) and NaCl and NaBr, respectively, were studied by isothermal in situ solid‐state NMR spectroscopy at 120, 130 and 140 °C with a time resolution of the order of 5 to 25 min. The nuclei probed were 23Na and 13C, allowing the parent compounds (sodium halogenoacetates) and both reaction products (polymer and alkali halide) to be monitored. For sodium chloroacetate, there is no evidence for the involvement of intermediate phases during the reaction whereas this cannot be excluded for sodium bromoacetate. The crystal structure of sodium bromoacetate was determined directly from powder diffraction data by the Monte Carlo method, and was found to be isostructural with sodium chloroacetate. The topochemical reaction mechanism proposed previously for sodium chloroacetate is thus also applicable for the polymerization reaction in sodium bromoacetate. The mechanistic and kinetic information obtained from our in situ solid‐state NMR investigations is compared and contrasted with information obtained from other in situ probes of the polymerization reactions in these materials.

A new approach is presented for the analysis of wideline ²H NMR lineshapes, based on automated fitting of simulated spectra to experimental spectra using either ‘downhill simplex’ or simulated annealing algorithms. This approach provides an objective assessment of the level of agreement between experimental and simulated ²H NMR spectra, and removes much of the subjectivity that is characteristic of the traditional approach involving trial-and-error variation of the parameters used in the simulation, followed by visual comparison between experimental and simulated ²H NMR spectra to assess the quality of fit. Applications of our new approach are reported for the analysis of (i) static ²H NMR powder patterns, (ii) the temperature dependence of ²H NMR powder patterns in the intermediate motion regime (including the case of fitting experimental spectra with poor signal-to-noise ratio) and (iii) the dependence of quadrupole echo ²H NMR spectra on the echo delay. Quantitative details relating to the dynamic properties of thiourea-d4 in its pure crystalline phase and in the chlorocyclohexane–thiourea-d4 inclusion compound are presented, in addition to the motion of the guest molecules in the benzenetricarbonylchromium-d6–thiourea inclusion compound and the pyrazine-d4–α-zirconium phosphate intercalation material. © 1998 John Wiley & Sons, Ltd.

Highly stable cyclic dimers have been assembled through a combination of non-covalent interactions, including multiple hydrogen bonding, parallel stacking and hydrophobic shielding.

The 2:1 reaction between Zn(O₂CMe)₂·2H₂O and 1-Meim in refluxing MeCN gives [Zn₇O₂(O₂CMe)₁₀(1-Meim)₂] 1 which comprises two vertex-sharing tetranuclear Zn₄(μ₄-O)(η¹: η¹:μ₂-O₂CMe)₅(1-Meim) units; solid-state ¹³C and ¹⁵N NMR spectra reveal structural details of the complex.

Triflic acid‐mediated cyclization of endocyclic N‐acyliminium ions towards aryl rings provides access towards benzazocinones, e.g. (III), (VI) or (XII).

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

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

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

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