Molecular structures of 3-hydroxybenzoic acid and 4-hydroxybenzoic acid, obtained by gas-phase electron diffraction and theoretical calculations

The structures of 3-hydroxybenzoic acid and 4-hydroxybenzoic acid have been determined by gas-phase electron diffraction using results from quantum chemical calculations to inform the choice of restraints applied to some of the structural parameters. The results from the study presented here demonstrate that resonance hybrids are not as helpful in rationalizing the structures of 2-, 3-, and 4-hydroxybenzoic acids as are models based upon electrostatic effects.     

Reactive intermediates in the H-phosphonate synthesis of oligonucleotides

The formation of H-phosphonate diesters is an important step in the synthesis of oligonucleotides. Using diphenylchlorophosphate as the activator for the coupling step is often accompanied by side reactions as a result of self 'capping' and other reactions of the reactive intermediate. In the absence of base, the activation of ethyl H-phosphonate with diphenylchlorophosphate probably occurs through the intermediate formation of bis diethyl pyro-di-H-phosphonate rather than the expected diphenyl ethyl pyro-H-phosphonate. Pyridine acts as a nucleophilic catalyst converting diphenylchlorophosphate to its pyridinium adduct. Several side and unwanted reactions are quantified so that conditions to minimise these can be identified.     

Destruction of Raman biosignatures by ionising radiation and the implications for life detection on Mars

Raman spectroscopy has proven to be a very effective approach for the detection of microorganisms colonising hostile environments on Earth. The ExoMars rover, due for launch in 2018, will carry a Raman laser spectrometer to analyse samples of the martian subsurface collected by the probe’s 2-m drill in a search for similar biosignatures. The martian surface is unprotected from the flux of cosmic rays, an ionising radiation field that will degrade organic molecules and so diminish and distort the detectable Raman signature of potential martian microbial life. This study employs Raman spectroscopy to analyse samples of two model organisms, the cyanobacterium Synechocystis sp. PCC 6803 and the extremely radiation resistant polyextremophile Deinococcus radiodurans, that have been exposed to increasing doses of ionising radiation. The three most prominent peaks in the Raman spectra are from cellular carotenoids: deinoxanthin in D. radiodurans and β-carotene in Synechocystis. The degradative effect of ionising radiation is clearly seen, with significant diminishment of carotenoid spectral peak heights after 15 kGy and complete erasure of Raman biosignatures by 150 kGy of ionising radiation. The Raman signal of carotenoid in D. radiodurans diminishes more rapidly than that of Synechocystis, believed to be due to deinoxanthin acting as a superior scavenger of radiolytically produced reactive oxygen species, and so being destroyed more quickly than the less efficient antioxidant β-carotene. This study highlights the necessity for further experimental work on the manner and rate of degradation of Raman biosignatures by ionising radiation, as this is of prime importance for the successful detection of microbial life in the martian near subsurface.     

Can MM‐PBSA calculations predict the specificities of protein kinase inhibitors?

An application of the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) protocol to the prediction of protein kinase inhibitor selectivity is presented. Six different inhibitors are placed in equivalent orientations in each of six different receptors. Fully solvated molecular dynamics is then run for 1 ns on each of the 36 complexes, and the resulting trajectories scored, using the implicit solvent model. The results show some correlation with experimentally-determined specificities; anomalies may be attributed to a variety of causes, including difficulties in quantifying induced fit penalties and variabilities in normal modes calculations. Decomposing interaction energies on a per-residue basis yields more useful insights into the natures of the binding modes and suggests that the real value of such calculations lies in understanding interactions rather than outright prediction.     

Conformational studies of tertiary oligo-m-benzanilides and oligo-p-benzanilides in solution

A series of oligo-m- and p-benzanilides were made and their conformations in solution were studied by NMR. In most cases, conformational mixtures were observed as soon as three or more monomers were incorporated into the oligomer. Some crystal structures were obtained, which indicated that helical conformations were adopted in the solid state.     

Ab Initio rovibrational spectrum of the NaH2 + ion–quadrupole complex

The electronic and rovibrational structure of (¹A₁) NaH₂ ⁺ has been investigated using a relativistically-corrected, all-electron coupled-cluster with singles, doubles and perturbative triples (CCSD(T)) ansatz. For the electronic ground state this ansatz yielded equilibrium Na–H bond lengths (R _e ) of 2.4208 Å and an equilibrium H–Na–H bond angle (θ_e) of 17.8°. An analytical potential energy surface (PES) was embedded in the rovibrational Hamiltonian. The PES was constructed using 118 CCSD(T) points and exhibited a residual error of 1.2 cm^?1. The rovibrational Hamiltonian was diagonalised using variational techniques. The vibrational and rovibrational eigenvectors were assigned using a configuration weight scheme in terms of normal modes and the Mulliken assignment scheme, respectively. For the ground vibrational state of (¹A₁) NaH₂ ⁺, the vibration-averaged bond lengths 〈R〉 and angle 〈θ〉 were 2.4995 Å and 17.1°, respectively. The ab initio (¹A₁) NaH₂ ⁺ PES yielded a dissociation energy (D ₀) value of 10.3 kJ mol^?1, which is in excellent agreement with the experimental value of 10.3 ± 0.8 kJ mol^?1 (Bushnell et al. in J Phys Chem 98:2044, 1994). An analytical dipole moment surface was constructed using 90 CCSD(T) points. Rovibrational spectra of (¹A₁) NaH₂ ⁺, (¹A′) NaHD⁺ and (¹A₁) NaD₂ ⁺ for v ≤ 10, J ≤ 5 were constructed using rovibrational transition moment matrix elements calculated in a novel manner that employs the analytical dipole moment surface (DMS). The rovibrational structure of the Na⁺–H₂ v _HH = 1 ← v _HH = 0 band was calculated and compared to that of Li⁺–H₂.