Study of the Phosphoryl‐Transfer Mechanism of Shikimate Kinase by NMR Spectroscopy

The phosphoryl‐transfer mechanism of shikimate kinase from Mycobacterium tuberculosis and Helicobacter pylori, which is an attractive target for antibiotic drug discovery, has been studied by 1D ¹H and ³¹P NMR spectroscopy. Metaphosphoric acid proved to be a good mimetic of the metaphosphate intermediate and facilitated the ready and rapid evaluation by NMR spectroscopic analysis of a dissociative mechanism. The required closed form of the active site for catalysis was achieved by the use of ADP (product) or two synthetic ADP analogues (AMPNP, AMPCP). Molecular dynamics simulation studies reported here also revealed that the essential arginine (Arg116/Arg117 in H. pylori and M. tuberculosis, respectively), which activates the γ‐phosphate group of ATP for catalysis and triggers the release of the product for turnover, would also be involved in the stabilisation of the metaphosphate intermediate during catalysis. We believe that the studies reported here will be helpful for future structure‐based design of inhibitors of this attractive target. The approach is also expected be useful for studies on the possible dissociative mechanism of other kinase enzymes.     

A heterometallic [LnLn′Ln] lanthanide complex as a qubit with embedded quantum error correction

We show that a [Er–Ce–Er] molecular trinuclear coordination compound is a promising platform to implement the three-qubit quantum error correction code protecting against pure dephasing, the most important error in magnetic molecules. We characterize it by preparing the [Lu–Ce–Lu] and [Er–La–Er] analogues, which contain only one of the two types of qubit, and by combining magnetometry, low-temperature specific heat and electron paramagnetic resonance measurements on both the elementary constituents and the trimer. Using the resulting parameters, we demonstrate by numerical simulations that the proposed molecular device can efficiently suppress pure dephasing of the spin qubits.

We show that a [Er–Ce–Er] molecular trinuclear coordination compound is a promising platform to implement the three-qubit quantum error correction code protecting against pure dephasing, the most important error in magnetic molecules.     

Predicting the Helical Sense of Poly(phenylacetylene)s from their Electron Circular Dichroism Spectra

The calculated ECD spectrum (time‐dependent density functional theory TD‐DFT) for small oligomers of polyphenylacetylenes (PPAs) show a very good match with the experimental spectra of the PPA polymers, particularly with the first Cotton band associated to the helical sense of the internal polyenic backbone. This has been proven with a series of PPAs representative of cis‐cisoidal, cis‐transoidal, compressed and stretched polyene backbones, with identical or opposite internal/external rotational senses and allows the prediction of the helical sense of the internal helix of a PPA directly from its CD spectra.     

Use of quasi-SMILES to model biological activity of “micelle–polymer” samples

The basic task of the drug discovery is the establishing of molecular structure of new pharmaceutical agents. To define the molecular structure is only half of the way to new drug. The transport of active molecules to appropriate targets in an organism should be elucidated in details. The selection of polymeric structures playing the role of basis for transport of therapeutic agents into the body is one of the ways to solve the task. Drug loading capacity (DLC) and critical micelle concentration (CMC) are measures of ability of “polymer–micelle” systems to be suitable for the process of the transport of therapeutic agents into an organism. Polymeric micelles are a type of complex multi-phase and multicomponent chemical process and can be used to transport drug into an organism. Prediction of ability of “micelle–polymer” systems to be a tool for transport of therapeutic agents to targets in organism is an important task. Models, which are a mathematical function of available eclectic information about architecture of micelles and polymers, are suggested. The eclectic data are represented via the so-called quasi-simplified molecular input-line entry system (SMILES), which are analogy of traditional SMILES. The quasi-SMILES contain some additional information besides the molecular architecture (physicochemical and biochemical conditions). Predictive potential of these models is good.

     

Spatial distribution of electrical conductivity and stable isotopes in groundwater in large catchments: a geostatistical approach in the Quequén Grande River catchment,Argentina

Stable isotopes and electrical conductivity in groundwater were used as natural tracers to adjust the hydrogeological conceptual model in one of the largest catchments within the inter-mountainous Pampa plain, Argentina. Geostatistical tools were used to define the model that best fitted the spatial distribution of each tracer, and information was obtained in areas where there was a lack of data. The conventional isotopic analysis allowed the identification of three groundwater groups with different isotopic fingerprints. One group containing 56?% of the total groundwater samples suggested a well-mixed system and soil infiltration precipitation as the main recharge source to the aquifer. The other two groups included samples with depleted (25.5?%) and enriched (18.5?%) isotopic compositions, respectively. The combination of δ¹⁸O, δ²H and electrical conductivities maps suggested ascending regional flows and water transfer from the Quequén Grande River catchment to the Moro creek. The spatial interpretation of these tracers modified the conceptual hydrogeological model of the Quequén Grande River.     

Conformational change and selectivity in explicitly hydrated carbohydrates

The combination of vibrational spectroscopy, conducted in a supersonic jet expansion, with computation through molecular mechanics, density functional theory (DFT) and ab initio calculation, has provided a new approach to the conformational and structural assignment of carbohydrates and their molecular complexes. This article reviews the new insights it has provided on the regioselectivity and conformational choice in singly and multiply hydrated monosaccharides. It reveals a systematic pattern of conformational preference and binding site selectivity, driven by the provision of optimal, co-operative hydrogen-bonded networks in the hydrated sugars. Water binding is invariably ’focused’ around the hydroxymethyl group (when present); the bound water molecules (on multiply hydrated mannose) are located exclusively on its hydrophilic face while the hydrophobic face remains ‘dry’; and there is a correlation between the locale of the preferred binding sites and those involved in protein–carbohydrate molecular recognition.     

Complexation of Apple Antioxidants: Chlorogenic Acid, Quercetin and Rutin by β-Cyclodextrin (β-CD)

The complexation and antioxidant activity of the major apple polyphenols: Chlorogenic Acid (CA), Rutin (Rt) and Quercetin (Qc) with β-cyclodextrin (β-CD) were studied, by fluorescence spectroscopy and Ferric Reducing/Antioxidant Power Assay (FRAP) techniques. All polyphenols formed 1:1 stoichiometry complexes. Their stability constants decreased in the order Qc (1138 M⁻¹) > CA (465 M⁻¹) > Rt (224 M⁻¹). The complex formation was also confirmed in the solid state by DSC measurements. Qc showed the highest antioxidant activity, followed by Rt and CA. In all cases, the complexation process produced a slight increment in their antioxidant activity (between 7 and 14%), more evident for Rt and CA than for Qc. *Part of this paper was presented at the Food Science and Food Biotechnology in Developing Countries Conference, Durango, Mexico, June 2004.     

Component analysis of the commercial metal extractant, Cyanex 302, by GC-MS.

The composition of the commercial reagent Cyanex 302 was investigated by GC-MS. Mass spectrometric studies allowed us to confirm that bis(2,4,4-trimethylpentyl)monothiophosphinic acid is the major compound and that a considerable amount of tris(2,4,4-trimethylpentyl)phosphine oxide is also present. The study also revealed that the extractant has three minor components. These were identified as bis(2,4,4-trimethylpentyl)phosphinic acid, bis(2,4,4-trimethylpentyl)phosphine oxide and bis(2,4,4-trimethylpentyl)dithiophosphinic acid. The mass spectra of these compounds are discussed and some fragmentation processes are postulated.     

Gas-phase structure of N,N-dimethylglycine.

Three conformers of the neutral amino acid N,N-dimethylglycine [(CH3)2NCH2COOH] were detected in a supersonic expansion by a combination of laser ablation (LA) and molecular-beam Fourier transform microwave (MB-FTMW) spectroscopy. A bifurcated methyl-to-carbonyl (C--HO==C) weak intramolecular hydrogen bond might stabilise the most stable conformer of C(s) symmetry. The second most stable conformer of C1 symmetry has a hydrogen bond between the hydroxyl group and the lone pair at the nitrogen atom (NH--O). The r(s) and r0 structures were derived for this conformer from the rotational data for the parent and six minor 13C, 15N and OD isotopomers. A third conformer exhibits a cis-carboxyl functional group and C1 symmetry. Ab initio MP2/6-311++G(d,p) predictions of the spectroscopic parameters were useful in analysing the spectra. In particular, the agreement of the nuclear quadrupole coupling constants with those calculated was conclusive in identifying the different conformers.