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I Alkorta

Publications and source records attributed to I Alkorta.

At least 19 recordsLinked to original sources
PubMed2001

A solid-state NMR, X-ray diffraction, and ab initio computational study of hydrogen-bond structure and dynamics of pyrazole-4-carboxylic acid chains.

Using high-resolution solid-state (15)N CMAS NMR, X-ray crystallography, and ab initio calculations, we have studied the structure of solid pyrazole-4-carboxylic acid (1). The crystal structure was determined at 295 and 150 K. Molecules of 1 are located on a two-fold axis, implying proton disorder of the NH and OH groups; no phase transition was observed between these two temperatures. The compound forms quasi-linear ribbons in which the molecules are linked by cyclic hydrogen bonds between pyrazole and carboxylic acid groups with disordered hydrogen-bonded protons. Crystallography is unable to decide whether the disorder is dynamic or static. NMR shows that this disorder is dynamic, that is, consisting of very fast degenerate double proton transfers between two rapidly interconverting O-H.N and O.H-N hydrogen bridges. However, at low temperature, NMR shows a proton disorder-order transition where the protons are preferentially localized on given nitrogen and oxygen atoms. An amorphous phase exhibiting proton order is observed when the compound is precipitated rapidly. In this case, the defects are annealed by moderate heating. Ab initio calculations performed on oligomers of 1 show that the O-H.N hydrogen bridge is about 0.064 A shorter and less bent ( approximately 171 degrees ) than the O.H-N hydrogen bridge ( approximately 150 degrees ). For an isolated ribbon, this result leads to structures with localized protons, either to a cycle with about 200 molecules, or to a quasi-linear ribbon involving an undulated structure, or to a combination of both motifs. Only the undulated structure is compatible with the linear ribbon observed by X-ray crystallography, where the fast proton transfer in the high-temperature phase is assisted by the motions of the undulated chain. A disordered structure is assigned to the amorphous phase, which exhibits the combination of the curved and the undulated motifs.

Journal Article↗
PubMed2001

Phytoextraction: a cost-effective plant-based technology for the removal of metals from the environment.

Phytoremediation is an emerging technology that uses plants to clean up pollutants (metals and organics) from the environment. Within this field of phytoremediation, the utilization of plants to transport and concentrate metals from the soil into the harvestable parts of roots and above-ground shoots is usually called phytoextraction. Most traditional remediation methods do not provide acceptable solutions for the removal of metals from soils. By contrast, phytoextraction of metals is a cost-effective approach that uses metal-accumulating plants to clean up these soils. Subsequently, the harvestable parts, rich in accumulated metals, can be easily and safely processed by drying, ashing or composting. Some extracted metals can also be reclaimed from the ash, generating recycling revenues. Phytoextraction appears a very promising technology for the removal of metal pollutants from the environment and may be, at present, approaching commercialization.

Biodegradation, Environmental↗
PubMed2001

Phytoremediation of organic contaminants in soils.

Soil pollution, a very important environmental problem, has been attracting considerable public attention over the last decades. Unfortunately, the enormous costs associated with the removal of pollutants from soils by means of traditional physicochemical methods have been encouraging companies to ignore the problem. Phytoremediation is an emerging technology that uses plants to clean up pollutants in the environment. As overwhelmingly positive results have become available regarding the ability of plants to degrade certain organic compounds, more and more people are getting involved in the phytoremediation of organic contaminants. Phytoremediation of organics appears a very promising technology for the removal of these contaminants from polluted sites.

Biodegradation, Environmental↗
PubMed2000

Novel bronchodilators: synthesis, transamination reactions, and pharmacology of a series of pyrazino[2,3-c][1,2,6]thiadiazine 2, 2-dioxides.

The synthesis, pharmacological evaluation, and structure-activity relationships of a new class of bronchodilator agents, derivatives of pyrazino[2,3-c][1,2,6]thiadiazine 2,2-dioxides are described. The compounds were prepared by reaction of 3,4,5-triamino-1,2, 6-thiadiazine 1,1-dioxide with suitable 1,2-dicarbonyl compounds or alpha-hydroxyiminoketones and subsequent N-alkylation. A transamination procedure for synthesizing derivatives with different substituents at the 4-amino group is reported for the first time. The pyrazino[2,3-c][1,2,6]thiadiazine derivatives were screened for tracheal relaxing activity in vitro, and the active compounds were evaluated in vivo in guinea pigs as bronchodilator agents in comparison to theophylline. Among the compounds studied, the most interesting properties were displayed by the 4-amino-1-ethyl-6-methyl derivative (21). The toxicological evaluation of this derivative is also reported.

Animals↗
PubMed2000

Vibrational spectra of 3,5-dimethylpyrazole and deuterated derivatives.

The infrared (IR) and Raman spectra of 3,5-dimethylpyrazole have been recorded in the vapor, liquid (melt and solution) and solid states. Two deuterated derivatives, C5H7N-ND and C5D7N-NH, were also studied in solid state and in solutions. Instrumental resolution was relatively low, 2.0 cm(-1) in the IR and approximately 2.7 cm(-1) in the Raman spectra. The solids are made of cyclic hydrogen-bonded trimers. These trimers, present also in chloroform and acetone solutions, give rise to characteristic high absorption IR spectra in the 3200-2500 cm(-1) region, related to Fermi resonance involving nu(NH) vibrations. Bands from trimers are not present in water solutions but these solutions show spectral features similar in several ways to those of the trimer, attributable to solvent-bonded complexes. Evidence of H-bonding interactions with the other solvents is also visible in the high-frequency region. The two very intense bands in the Raman spectra of the solids appearing at 115 and 82 cm(-1) in the parent compound are also connected with a trimer formation. To interpret the experimental data, ab initio computations of the harmonic vibrational frequencies and IR and Raman intensities were carried out using the Gaussian 94 program package after full optimization at the RHF/6-31G* level for the three monomeric compounds as well as for three models of the trimer, with C3h, C3 and C1 symmetry. The combined use of experiments and computations allow a firm assignment of most of the observed bands for all the systems. In general, the agreement between theory and experiment is very good, with the exception of the IR and Raman intensities of some transitions. Particularly noticeable is the failure of the theoretical calculation in accounting for the high intensity of the Raman bands of the solid about 115 and 82 cm(-1).

Deuterium↗
PubMed2000

Supramolecular structure of 1H-pyrazoles in the solid state: a crystallographic and ab initio study.

The secondary structure of 1H-unsubstituted pyrazole derivatives bearing only one hydrogen donor group and one or more acceptor groups has been analyzed in terms of some descriptors representing the substituents at C3 and C5. The substituent at C4 appears to affect mainly the tertiary or quaternary structure of these compounds. The proposed semi-quantitative model, which explains most hydrogen-bonded motifs as a combination of the effects of substituents at C3 and C5, has also been examined as a function of the steric and polarizability effects of these substituents represented by molar refractivity. The model also applies to other five-membered rings (1,2,4-triazoles, 1,2,4-diazaphospholes and 1,2, 4-diazaarsoles). Furthermore, ab initio calculations at RHF/6-31G* have been performed to discover the relative stability of three of the four hydrogen-bond patterns displayed by several symmetrical pyrazoles (dimers, trimers, tetramers). The fourth motif, catemers, has only been discussed geometrically.

Crystallography, X-Ray↗
PubMed1999

Characterization of ATP and DNA binding activities of TrwB, the coupling protein essential in plasmid R388 conjugation.

TrwB is the conjugative coupling protein of plasmid R388. TrwBDeltaN70 contains the soluble domain of TrwB. It was constructed by deletion of trwB sequences containing TrwB N-proximal transmembrane segments. Purified TrwBDeltaN70 protein bound tightly the fluorescent ATP analogue TNP-ATP (K(s) = 8.7 microM) but did not show measurable ATPase or GTPase activity. A single ATP binding site was found per TrwB monomer. An intact ATP-binding site was essential for R388 conjugation, since a TrwB mutant with a single amino acid alteration in the ATP-binding signature (K136T) was transfer-deficient. TrwBDeltaN70 also bound DNA nonspecifically. DNA binding enhanced TrwC nic cleavage, providing the first evidence that directly links TrwB with conjugative DNA processing. Since DNA bound by TrwBDeltaN70 also showed increased negative superhelicity (as shown by increased sensitivity to topoisomerase I), nic cleavage enhancement was assumed to be a consequence of the increased single-stranded nature of DNA around nic. The mutant protein TrwB(K136T)DeltaN70 was indistinguishable from TrwBDeltaN70 with respect to the above properties, indicating that TrwB ATP binding activity is not required for them. The reported properties of TrwB suggest potential functions for conjugative coupling proteins, both as triggers of conjugative DNA processing and as motors in the transport process.

Adenosine Triphosphate↗
PubMed1999

Rhodobacter capsulatus DNA topoisomerase I purification and characterization.

A 30-kDa DNA topoisomerase has been purified to near homogeneity from the purple nonsulfur photosynthetic bacterium Rhodobacter capsulatus. The enzyme is recognized by an antibody against a 16-mer peptide sequence from human DNA topoisomerase I. The purified enzyme is a type I topoisomerase. Consistent with the properties of other prokaryotic type I DNA topoisomerases, the isolated enzyme is unable to relax positively supercoiled DNA and absolutely requires divalent cations for its relaxation activity. However, regardless of the Mg+2 concentrations, ATP concentrations above 5 mM completely inhibit the relaxing activity. The enzyme is sensitive to high salt concentrations and the optimal activity occurs at salt concentrations between 3 and 30 mM for monovalent cations. Single-stranded M13 DNA is a strong inhibitor of this relaxing activity. The enzyme is inhibited by ethidium bromide, confirming that this DNA topoisomerase is incapable of relaxing positive supercoils. Topoisomerase I-specific inhibitors like Hoechst 32258 and actinomycin D inhibit the enzymatic activity while the enzyme is resistant to type II topoisomerase inhibitors such as norfloxacin, nalidixic acid, and novobiocin. From these enzymatic characteristics, we conclude that the R. capsulatus DNA topoisomerase is a prokaryotic type I DNA topoisomerase.

Bacterial Proteins↗
PubMed1998

Similarity studies on guanidinium, imidazolinium, and imidazolium cations: toward new bradykinin antagonists.

Bradykinin (BK) is a potent nociceptive agent and its antagonists show analgesic activity. In the search for new antagonists of BK, the design of nonpeptidic derivatives with different terminal cations has been considered. Among these new antagonists, the guanidinium cations, which appear not only in the terminal arginine residues of BK but also in several nonpeptidic antagonists, will be substituted by groups with characteristics similar in terms of electrostatic potential, electron density, shape, etc. Several similarity indexes have been calculated for guanidinium, 2-aminoimidazolinium, and 2-aminoimidazolium cations and their corresponding neutral species to design new nonpeptidic BK antagonists. The geometric and electronic characteristics of the molecules were compared by means of: (1) the Carbo index, (2) the Hodgkin index, and (3) a shape similarity index based on the volume of each molecule as defined by a certain electron density. Molecular geometries and energies were optimized by ab initio calculations at the B3LYP/6311+2G** level. The molecular electrostatic potential (MEP) and the electron density (rho) were then computed in a cubic grid of points around each molecule. These molecular properties were used to calculate similarity indexes with the guanidinium cation or guanidine as the reference molecule in each family. In addition, three-dimensional similarity maps were generated to localize those molecular areas more alike in each of the sets.

Bradykinin↗
PubMed1998

Aerobic chromate reduction by Bacillus subtilis.

We have studied the reduction of hexavalent chromium (chromate) to the less toxic trivalent form by using cell suspensions and cell-free extracts from the common soil bacterium, Bacillus subtilis. B. subtilis was able to grow and reduce chromate at concentrations ranging from 0.1 to 1 mM K2CrO4. Chromate reduction was not affected by a 20-fold excess of nitrate-compound that serves as alternate electron acceptor and antagonizes chromate reduction by anaerobic bacteria. Metabolic poisons including sodium azide and sodium cyanide inhibited chromate reduction. Reduction was effected by a constitutive system associated with the soluble protein fraction and not with the membrane fraction. The reducing activity was heat labile and showed a Km of 188 microns CrO4(2)-. The reductase can mediate the transfer of electrons from NAD(P)H to chromate. The results suggest that chromate is reduced via a detoxification system rather than dissimilatory electron transport.

Aerobiosis↗
PubMed1997

Heterocyclic structures useful in medicinal chemistry: the case of pyrazino[2,3-c][1,2,6]thiadiazine 2,2-dioxide.

Different aspects of a particular kind of heterocycle, namely pyrazino[2,3-c][1,2,6]thiadiazine 2,2-dioxide are discussed. These include synthesis, reactivity, tautomerism and acid-base properties, results of x-ray analysis and molecular orbital calcultations. Besides, some of the derivatives have shown interesting biological effects, among which are the diuretic properties which are also presented.

Animals↗
PubMed1997

Selenite bioremediation potential of indigenous microorganisms from industrial activated sludge.

Ten bacterial strains were isolated from the activated sludge waste treatment system (BIOX) at the Exxon refinery in Benicia, California. Half of these isolates could be grown in minimal medium. When tested for selenite detoxification capability, these five isolates (members of the genera Bacillus, Pseudomonas, Enterobacter and Aeromonas), were capable of detoxifying selenite with kinetics similar to those of a well characterized Bacillus subtilis strain (168 Trp+) studied previously. The selenite detoxification phenotype of the Exxon isolates was stable to repeated transfer on culture media which did not contain selenium. Microorganisms isolated from the Exxon BIOX reactor were capable of detoxifying selenite. Treatability studies using the whole BIOX microbial community were also carried out to evaluate substrates for their ability to support growth and selenite bioremediation. Under the appropriate conditions, indigenous microbial communities are capable of remediating selenite in situ.

Aeromonas↗
PubMed1996

A 3D model of the delta opioid receptor and ligand-receptor complexes.

A model for the 3D structure of the transmembrane domain of the delta opioid receptor was predicted from the sequence divergence analysis of 42 sequences of G-protein coupled peptide hormone receptors belonging to the opioid, somatostatin and angiotensin receptor families. No template was used in the prediction steps, which include multiple sequence alignment, calculation of a variability profile of the aligned sequences, use of the variability profile to identify the boundaries of transmembrane regions, prediction of their secondary structure, optimization of the packing shape in a helix bundle, prediction of side chain conformations and structural refinement. The general shape of the model is similar to that of the low resolution rhodopsin structure in that the TM3 and TM7 helices are most buried in the bundle and the TM1 and TM4 helices are most exposed to the lipid phase. An initial assessment of this model was made by determining to what extent a binding site identified using four structurally disparate high affinity delta opioid ligands was consistent with known mutational studies. With the assumption that the protonated amine nitrogen, a feature common to all delta opioid ligands, interacts with the highly conserved Asp127 in TM3, a pocket was found that satisfied the criteria of complementarity to the requirements for receptor recognition for these four diverse ligands, two delta selective antagonists (the fused ring naltrindole and the peptide Tyr-Tic-Phe-Phe-NH2) and the two agonists lofentanil and BW373U86 deduced from previous studies of the ligands alone. These ligands could be accommodated in a similar region of the receptor. The receptor binding site identified in the optimized complexes contained many residues in positions known to affect ligand binding in G-protein coupled receptors. These results also allowed identification of key residues as candidates for point mutations for further assessment and refinement of this model as well as preliminary indications of the requirements for recognition of this receptor.

Amino Acid Sequence↗
PubMed1994

Molecular electrostatic potential of D1 and D2 dopamine agonists.

The molecular electrostatic potential (MEP) of four selective D1, four nonselective D1/D2, and three selective D2 agonists has been calculated in a three-dimensional grid surrounding the molecules. The local density functional program DMol was used to evaluate the MEP. A comparison of the MEPs of all compounds revealed that while the electrostatic effects may be important for the affinity in both D1- and D2-selective ligands, it only appears to be a subtle modulator of the selectivity. Slight differences were found in the negative regions in the vicinity of the catechol ring that can account for the D1 versus D2 selectivity in the compounds studied.

Dopamine Agents↗
PubMed1994

Molecular polarization maps as a tool for studies of intermolecular interactions and chemical reactivity.

Maps for the interaction energy of acetone, pyrrole, furan, and pyridine with a positive unitary charge were computed using ab initio techniques, together with their molecular electrostatic potentials at the same points. The difference between the interaction and electrostatic potential maps yielded polarization maps for the molecules. Finally, maps for the interaction with a negative charge were obtained as the difference between the polarization and electrostatic potential maps. The calculations were carried out for three planes, 2 Bohr radii, 4 Bohr radii, and 8 Bohr radii from the plane containing the heavy atoms for all the molecules. At larger distances, the interaction and electrostatic maps resemble each other qualitatively; however, at shorter distances, where the polarization effects are more significant, the differences between the maps are notable. Interaction and polarization maps can be routinely evaluated for medium-sized molecules, and are likely to become an important tool in drug design and chemical reactivity.

Acetone↗
PubMed1994

Sequence divergence analysis for the prediction of seven-helix membrane protein structures: I. Comparison with bacteriorhodopsin.

A method using protein sequence divergence to predict the three-dimensional structure of the transmembrane domain of seven-helix membrane proteins is described. The key component in the multistep procedure is the calculation of a hydrophilic and lipophilic variability index for each amino acid in an alignment of a family of homologous proteins. The variability profile, a plot of the calculated variability index versus alignment position, can be used to predict a tertiary model of the backbone conformation of the transmembrane domain. This method was applied to bacteriorhodopsin (BR) and the model obtained was compared with the known structure of this protein. Using an alignment of the amino acid sequences of BR and closely related (> or = 20% identity) proteins, the boundaries of the transmembrane regions, their secondary structures and orientations inside the membrane bilayer were predicted based on the variability profile. Additional information about the shape of the helix bundle was also obtained from the average variability of each transmembrane helix with the assumption that the helices are packed sequentially and form a closed helix bundle. Correct features of the known structure of BR were found in the model structure, suggesting that a similar strategy can be used to predict transmembrane helices and the packing shape of other membrane proteins with seven transmembrane helices, such as the opsins and other G-protein coupled receptors.

Amino Acid Sequence↗
PubMed1994

Sequence divergence analysis for the prediction of seven-helix membrane protein structures: II. A 3-D model of human rhodopsin.

A three-dimensional (3-D) model of the transmembrane domain of human rhodopsin was predicted from the sequence divergence analysis of 42 sequences of rhodopsins and visual pigments without a template. The prediction steps include multiple sequence alignment, calculation of a variability profile of the aligned sequences, use of the variability profile to identify the boundaries of transmembrane regions, their secondary structure and packing shape in a helix bundle, prediction of side-chain conformations and structure refinement. The identification of the retinal binding site was assisted by its known covalent linkage with K296. The structural features of the predicted 3-D model are in good agreement with a low resolution electron density map of bovine rhodopsin and with residues in contact with retinal as determined experimentally.

Amino Acid Sequence↗