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The conformational preferences of N‐((6‐methylpyridin‐2‐yl)carbamothioyl)benzamide were studied in solution, the gas phase and the solid state via a combination of NMR, density functional theory (DFT) and single crystal X‐ray techniques. This acyl thiourea derivative can adopt two classes of low energy conformation, each stabilized by a different 6‐membered intramolecular hydrogen bond (IHB) pseudoring. Analysis in different solvents revealed that the conformational preference of this molecule is polarity dependent, with increasingly polar environments yielding a higher proportion of the minor conformer containing an NH⋅⋅⋅N IHB. The calculated barrier to interconversion is consistent with dynamic behaviour at room temperature, despite the propensity of 6‐membered IHB pseudorings to be static. This work demonstrates that introducing competitive IHB pathways can render static IHBs more dynamic and that such systems could have potential as chameleons in drug design. [ABSTRACT FROM AUTHOR]

Different molecular balances were designed previously to compare noncovalent interactions. However, some balances are difficult to synthesise and there is a need for developing a computational approach. In this work, we probe noncovalent interactions of π systems using DFT methods to assess their reliability in reproducing experimentally measured conformer populations. Based on our results, the PW6B95D3 functional performed best, followed by M11L and ωB97XD. Additionally, the simulation of the rotation of the hydroxyl group revealed stabilising OH⋯Alkyne and OH⋯Nitrile interactions that are difficult to identify experimentally. These methods were then applied to compare the strengths of sulfur⋯π interactions in molecules which have not been explored experimentally. Compared to the hydroxyl counterpart, the simulation of the thiol group rotation showed that the geometry of the conformer with the two sulfur lone pairs oriented towards the aromatic ring or the double bond is stabilised, suggesting that S(LP)⋯π interactions can be attractive in nature. The ability of sulfur to rearrange its electronic surrounding to form an attractive interaction with π systems, including those with either electron‐donating or withdrawing groups, was also confirmed. Overall, the results show a promising future for both qualitative and quantitative assessments of the strengths of noncovalent interactions using selected DFT techniques. [ABSTRACT FROM AUTHOR]

Herein we report a fundamental discovery on the use of tris(dialkylamino)phosphine reagents for peptide and protein modification. We discovered that C-terminal thiophosphonium species, which are uniquely stable, could be selectively and rapidly generated from their disulfide counterparts. In sharp and direct contrast, internal thiophosphonium species rapidly degrade to dehydroalanine. We demonstrate this remarkable chemoselectivity on a bis-cysteine model peptide, and the formation of a stable C-terminal-thiophosphonium adduct on an antibody fragment, as well as characterise the species in various small molecule/peptide studies. [ABSTRACT FROM AUTHOR]

Solid-State (super 13)C NMR and (super 2)H NMR techniques are used to investigate structural and dynamic properties of hydrogen-bonded complexes or sheets, inclusion compound and pure crystalline phase of urea. Ribbons of urea molecules alternating with ribbons of alpha,omega-dicyanoalkane molecules are present within each sheet.

The synthetic approaches to ureidopyrimidinones possessing p-aminophenyl groups at C-6, and an alkyl or hydrophilic side chain at R(sub 2), as well as an azo-derivative, are described. The studies investigating the tautomeric distributions of the compounds prepared are also presented.

Dynamic properties of the hydroxyl groups in a selectively deuterated sample of triphenylsilanol (Ph3SiOD) are studied using variable-temperature solid-state (super 2)H NMR spectroscopy. The crystal structure of triphenylsilanol contains eight crystallographically independent molecules, which are arranged in two tetrameric building units.

Research was conducted to examine the structural characterization of the hydrogen-bonding arrangement in triphenylmethanol via single-crystal neutron diffraction, single-crystal X-ray diffraction and high-resolution solid-state 13C NMR spectroscopy. An accurate determination of the positions of the hydrogen atoms in the hydrogen-bonding arrangement was obtained by the single-crystal neutron diffraction experiments while the single-crystal X-ray diffraction experiments have extended previous studies across a wider temperature range. The high-resolution solid-state 13C NMR experiments have provided insights into local structural aspects of the hydrogen-bonded tetramers.

The energy obstacles for a 'chair-chair' ring inversion mechanism, that was shown by temperature-dependent variations in high-resolution solid state C NMR spectra of thiourea inclusion compounds to take place in monosubstituted cyclohexane guest molecules within the thiourea tunnel, were identified. The NMR spectra recorded in slow exchange settings directly established the comparative populations of the axial and equational conformers of the guest molecules. The equational conformer is found primarily in guest molecules with X = CH3, NH2 and OH, while the axial conformer is found primarily in those with X = Cl, Br and I.

Research has been conducted on the guanosine, inosine and the metal complexes formed between Na (super)+, Ba (super)+ and Cd (super)2+ and the mononucleotides. The sensitivity of (super)15 N shielding to metal ion coordination has been investigated and the results are presented.

The palladium‐catalysed sp3 C−H arylation of a selection of saturated amine scaffolds was investigated using substituted picolinamide directing groups. On the bornylamine scaffold, highly selective monoarylation takes place using unsubstituted picolinamide or 3‐methylpicolinamide, whereas a double C−H arylation occurs with other substituents present, becoming a significant product with 3‐trifluoromethylpicolinamide. DFT calculations were used to help rationalise the effect of directing groups on the C−H palladation steps which were found experimentally to be irreversible. The substituted picolinamide directing groups were also examined on acyclic amine scaffolds and in many cases increased yields and selectivity could be obtained using methylpicolinamides. For a selection of other amine scaffolds, the yield of C−H arylation could be improved significantly using 3‐methylpicolinamide as the directing group and/or 3‐methylpentan‐3‐ol as the solvent [ABSTRACT FROM AUTHOR]