Queratomileusis in situ asistida por Láser de Excímeros en la corrección del Astigmatismo Miópico / Excimer laser-assisted in situ keratomileusis for correction of myopic astigmatism

Introducción: la queratomielusis es un procedimiento quirúrgico de valor en el tratamiento de las ametropías.Objetivo: determinar los resultados de la queratomileusis "in situ" asistida por láser de excímeros (LASIK) en la corrección del astigmatismo miópico.Métodos: se realizó un estudio retrospectivo de 73 pacientes con astigmatismo miópico, operados con la técnica LASIK durante el año 2013 en el Hospital Militar Dr. Carlos J. Finlay. Las variables fueron: edad, sexo, agudeza visual con corrección pre y postoperatorias, equivalente esférico, complicaciones trans-operatorias, postoperatorias inmediatas y tardías. Para el procesamiento de la información se utilizó programa SPSS. Resultados: se mantuvo la agudeza visual previa corregida y no se detectaron complicaciones graves o irreversibles. Se observaron cambios significativos en las variables estudiadas con tendencia a la emetropía para un 92,3 por ciento.Conclusión: LASIK es una técnica segura y útil para la corrección del astigmatismo miópico, que permite mejorar la agudeza visual(AU)

Objetive: to determinate the results of ExcÝmer laser assisted ôin situõ keratomileusis (LASIK)in the correction of myopic astigmatism. Methods: a descriptive, retrospective study of the results was performed after surgery LASIK in 73 patients with myopic astigmatism. The variables were: age, sex, pre and postoperative visual acuity without correction, spherical equivalent, intraoperative complications, postoperative immediate and late complications. Significant changes were observed in all the variables studied tending to emmetropia and 92.3 percent. Results: with the use of this surgical technique the corrected previous visual acuity remained and not serious or irreversible complications were detected.Conclusions: Lasik is a safe and useful technique for the correction of myopic astigmatism that improves visual acuity(AU)

Queratomileusis in situ asistida por láser de excímeros en la corrección del astigmatismo miópico / Excimer laser-assisted in situ keratomileusis for correction of myopic astigmatism

INTRODUCCIÓN: la queratomielusis es un procedimiento quirúrgico de valor en el tratamiento de las ametropías. OBJETIVO: determinar los resultados de la queratomileusis "in situ" asistida por láser de excímeros (LASIK) en la corrección del astigmatismo miópico. MÉTODOS: se realizó un estudio retrospectivo de 73 pacientes con astigmatismo miópico, operados con la técnica LASIK durante el año 2013 en el Hospital Militar "Dr. Carlos J. Finlay". Las variables fueron: edad, sexo, agudeza visual con corrección pre y postoperatorias, equivalente esférico, complicaciones trans-operatorias, postoperatorias inmediatas y tardías. Para el procesamiento de la información se utilizó programa SPSS. RESULTADOS: se mantuvo la agudeza visual previa corregida y no se detectaron complicaciones graves o irreversibles. Se observaron cambios significativos en las variables estudiadas con tendencia a la emetropía para un 92,3 %. CONCLUSIÓN: LASIK es una técnica segura y útil para la corrección del astigmatismo miópico, que permite mejorar la agudeza visual.

OBJETIVE: to determinate the results of Excímer laser assisted "in situ" keratomileusis (LASIK)in the correction of myopic astigmatism. METHODS: a descriptive, retrospective study of the results was performed after surgery LASIK in 73 patients with myopic astigmatism. The variables were: age, sex, pre and postoperative visual acuity without correction, spherical equivalent, intraoperative complications, postoperative immediate and late complications. Significant changes were observed in all the variables studied tending to emmetropia and 92.3 %. RESULTS: with the use of this surgical technique the corrected previous visual acuity remained and not serious or irreversible complications were detected. CONCLUSIONS: Lasik is a safe and useful technique for the correction of myopic astigmatism that improves visual acuity.

Chemoselective intramolecular functionalization of methyl groups in nonconstrained molecules promoted by N-iodosulfonamides.

Mechanistic evidence observed in Hofmann-Löffler-Freytag-type reactions has been crucial to achieve the chemoselective functionalization of methyl groups under mild conditions. Radical-mediated methyl iodination and subsequent oxidative deiodination are the key steps in this functionalization, where iodine chemistry has a pivotal role on the formation of the C-N bond. The concepts of single hydrogen atom transfer (SHAT) and multiple hydrogen atom transfer (MHAT) are introduced to describe the observed chemoselectivity.

Unraveling the molecular structure of the catalytic domain of matrix metalloproteinase-2 in complex with a triple-helical peptide by means of molecular dynamics simulations.

Herein, we present the results of a computational study that employed various simulation methodologies to build and validate a series of molecular models of a synthetic triple-helical peptide (fTHP-5) both in its native state and in a prereactive complex with the catalytic domain of the MMP-2 enzyme. First, the structure and dynamical properties of the fTHP-5 substrate are investigated by means of molecular dynamics (MD) simulations. Then, the propensity of each of the three peptide chains in fTHP-5 to be distorted around the scissile peptide bond is assessed by carrying out potential of mean force calculations. Subsequently, the distorted geometries of fTHP-5 are docked within the MMP-2 active site following a semirigid protocol, and the most stable docked structures are fully relaxed and characterized by extensive MD simulations in explicit solvent. Following a similar approach, we also investigate a hypothetical ternary complex formed between two MMP-2 catalytic units and a single fTHP-5 molecule. Overall, our models for the MMP-2/fTHP-5 complexes unveil the extent to which the triple helix is distorted to allow the accommodation of an individual peptide chain within the MMP active site.

Ab initio benchmark calculations on Ca(II) complexes and assessment of density functional theory methodologies.

A set of benchmark results for the geometries, binding energies, and protonation affinities of 24 complexes of small organic ligands with Ca(II) is provided. The chosen level of theory is CCSD(T)/CBS obtained by means of a composite procedure. The performance of four density functionals, namely, PW91, PBE, B3LYP, and TPSS and several Pople-type basis sets, namely, 6-31G(d), 6-31+G(d), 6-31+G(2d,p) and 6-311+G(d) have been assessed. Additionally, the nature of the metal ligand bonding has been analyzed by means of the Symmetry Adapted Perturbation Theory (SAPT). We have found that the B3LYP hybrid functional, in conjunction with either the polarized double-ζ 6-31+G(2d,p) or the triple-ζ 6-311+G(d) basis sets, yields the closest results compared to the benchmark data. The SAPT analysis stresses the importance of induction effects in the binding of these complexes and suggests that consideration of classical electrostatic contributions alone may not be reliable enough for the prediction of relative binding energies for Ca(II) complexes.

Ketone-alcohol hydrogen-transfer equilibria: is the biooxidation of halohydrins blocked?

To ensure the quasi-irreversibility of the oxidation of alcohols coupled with the reduction of ketones in a hydrogen-transfer (HT) fashion, stoichiometric amounts of α-halo carbonyl compounds have been employed as hydrogen acceptors. The reason that these substrates lead to quasi-quantitative conversions has been tacitly attributed to both thermodynamic and kinetic effects. To provide a clear rationale for this behavior, we investigate herein the redox equilibrium of a selected series of ketones and 2-propanol by undertaking a study that combines experimental and theoretical approaches. First, the activity of the (R)-specific alcohol dehydrogenase from Lactobacillus brevis (LBADH) with these substrates was studied. The docking of acetophenone/(R)-1-phenyethanol and α-chloroacetophenone/(S)-2-chloro-1-phenylethanol in the active site of the enzyme confirms that there seems to be no structural reason for the lack of reactivity of halohydrins. This assumption is confirmed by the fact that the corresponding aluminum-catalyzed Meerwein-Ponndorf-Verley-Oppenauer (MPVO) reactions afford similar conversions to those obtained with LBADH, showing that the observed reactivity is independent of the catalyst employed. While the initial rates of the enzymatic reductions and the IR ν(C=O) values contradict the general belief that electron-withdrawing groups increase the electrophilicity of the carbonyl group, the calculated ΔG values of the isodesmic redox transformations of these series of ketones/alcohols with 2-propanol/acetone support the thermodynamic control of the reaction. As a result, a general method to predict the degree of conversion obtained in the HT-reduction process of a given ketone based on the IR absorption band of the carbonyl group is proposed, and a strategy to achieve the HT oxidation of halohydrins is also shown.

Experimental and theoretical investigation of the aromatic-aromatic interaction in isolated capped dipeptides.

Among the forces responsible for shaping proteins, interactions between side chains of aromatic residues play an important role as they are involved in the secondary and the tertiary structures of proteins contributing to the formation of hydrophobic domains. The purpose of this paper is to document this interaction in two capped dipeptides modeling a segment of a protein chain having two consecutive Phe residues, Ac-Phe-Phe-NH(2) and Ac-Phe-D-Phe-NH(2). These two molecules have been investigated in the gas phase by IR/UV double resonance spectroscopy, and the assignment of the observed conformers has been done by comparison with quantum chemistry calculations. Both peptides are found to adopt a beta-turn type I conformation stabilized by an edge-to-face interaction between the two aromatic rings. Comparison with other dipeptides in the literature demonstrates the impact of this aromatic-aromatic interaction on the shape adopted by the peptide chain, and its role among the other shaping forces (H-bonds, NH-pi interactions) is discussed. As an illustration, the H-bond strength is found to be significantly lower in the beta-turn type I conformer, in which the two rings interact, as compared to the similar conformer where such an interaction does not exist. This structural feature due to the backbone distortion induced by the interaction between the aromatic rings makes this system a good test for evaluating the ability of computational methods to correctly account for the competition between these forces. MP2, SCS-MP2, DFT, and DFT-D methods have been assessed in this respect. Comparison between geometries, energies, and frequency calculations illustrate their respective limitations in describing conformations resulting from a subtle equilibrium between the several interactions at play.

Interdomain Conformations in the Full-Length MMP-2 Enzyme Explored by Protein-Protein Docking Calculations Using pyDock.

Current understanding of the collagenolytic activity performed by the matrix metalloproteinases (MMPs) assumes some degree of relative motion between their catalytic and hemopexin-like domains, according to evidence from low-resolution techniques for some of the MMP family members. Herein, we employ protein-protein docking calculations to investigate the structure in aqueous solution of the full-length MMP-2 enzyme in its active form, for which there is not yet experimental evidence of interdomain movement. After docking the domains as free rigid-body subunits, the linker region connecting the catalytic and hemopexin-like domains is taken into account a posteriori by merely adding an empiric energy term computed from expected end-to-end distance to the scoring function. Finally, full-length MMP-2 structures are generated by model building the linker residues in the most stable docking poses. The results add support to the hypothesis that the interdomain dynamics of a single MMP-2 molecule in aqueous solution can result in a manifold of conformations, with some preferred orientations. Globally, this structural information could be helpful in future experimental or computational studies aimed to elucidate the dynamical behavior of the MMP-2 enzyme in solution.

Polyisocyanides of titanium.

Neutral Ti[CN](n) complexes have been investigated with quantum chemistry techniques. According to our theoretical predictions, these complexes are shown to prefer isocyanide arrangements. Therefore, these compounds are good candidates to be the first polyisocyanides to be characterized. The theoretical calculations predict Ti(NC)(4), a methane-like tetrahedral structure with four isocyanide ligands, as the most stable neutral complex. The fact that the isocyanide ligand is a better pi-donor than the cyanide one seems to be the key factor for the preference for isocyanides in neutral titanium complexes.

From the X-ray compact structure to the elongated form of the full-length MMP-2 enzyme in solution: a molecular dynamics study.

Current understanding on the collagenolytic activity performed by the MMPs assumes some degree of relative motion between the catalytic and the hemopexin-like domains of the enzyme. However, all the crystal structures available for the full-length enzymes display a compact arrangement of the protein domains. Herein, we employ Molecular Dynamics simulations to investigate the structure of the full-length MMP-2 enzyme in aqueous solution. This simulation, together with previous experimental results that have been obtained very recently for the MMP-9 and MMP-12 enzymes, gives strong support to the hypothesis that the interdomain dynamics of the MMP enzymes in solution can result in a manifold of conformations including some structures with a large interdomain separation. The simulation of MMP-2 provides also a detailed molecular picture of the structures involved in the transition from the compact X-ray arrangement to the extended form in solution. Such information could be helpful in future studies of the regulation and/or the collagenolytic activity of these important enzymes.

Benchmark database on isolated small peptides containing an aromatic side chain: comparison between wave function and density functional theory methods and empirical force field.

A detailed quantum chemical study on five peptides (WG, WGG, FGG, GGF and GFA) containing the residues phenylalanyl (F), glycyl (G), tryptophyl (W) and alanyl (A) -- where F and W are of aromatic character -- is presented. When investigating isolated small peptides, the dispersion interaction is the dominant attractive force in the peptide backbone-aromatic side chain intramolecular interaction. Consequently, an accurate theoretical study of these systems requires the use of a methodology covering properly the London dispersion forces. For this reason we have assessed the performance of the MP2, SCS-MP2, MP3, TPSS-D, PBE-D, M06-2X, BH&H, TPSS, B3LYP, tight-binding DFT-D methods and ff99 empirical force field compared to CCSD(T)/complete basis set (CBS) limit benchmark data. All the DFT techniques with a '-D' symbol have been augmented by empirical dispersion energy while the M06-2X functional was parameterized to cover the London dispersion energy. For the systems here studied we have concluded that the use of the ff99 force field is not recommended mainly due to problems concerning the assignment of reliable atomic charges. Tight-binding DFT-D is efficient as a screening tool providing reliable geometries. Among the DFT functionals, the M06-2X and TPSS-D show the best performance what is explained by the fact that both procedures cover the dispersion energy. The B3LYP and TPSS functionals-not covering this energy-fail systematically. Both, electronic energies and geometries obtained by means of the wave-function theory methods compare satisfactorily with the CCSD(T)/CBS benchmark data.

Non-standard base pairing and stacked structures in methyl xanthine clusters.

We present resonant two-photon ionization and IR-UV double resonance spectra of methylated xanthine derivatives including 7-methylxanthine dimer and theobromine dimer seeded in a supersonic jet by laser desorption. For 7-methylxanthine, theophylline and theobromine monomer we assign the lowest energy tautomer based on comparison with IR-UV double resonance spectra and calculated IR frequencies. For the 7-methylxanthine dimer, we observe hydrogen bonding on the N3H position suggesting 3 possible combinations, one that is reverse Watson-Crick type and two that are reverse Hoogsteen type. For the theobromine dimer, we observe a stacked structure. For trimethylxanthine dimers we infer a stacked structure as well.

Potential-energy and free-energy surfaces of glycyl-phenylalanyl-alanine (GFA) tripeptide: experiment and theory.

The free-energy surface (FES) of glycyl-phenylalanyl-alanine (GFA) tripeptide was explored by molecular dynamics (MD) simulations in combination with high-level correlated ab initio quantum chemical calculations and metadynamics. Both the MD and metadynamics employed the tight-binding DFT-D method instead of the AMBER force field, which yielded inaccurate results. We classified the minima localised in the FESs as follows: a) the backbone-conformational arrangement; and b) the existence of a COOH...OC intramolecular H-bond (families CO(2)H(free) and CO(2)H(bonded)). Comparison with experimental results showed that the most stable minima in the FES correspond to the experimentally observed structures. Remarkably, however, we did not observe experimentally the CO(2)H(bonded) family (also predicted by metadynamics), although its stability is comparable to that of the CO(2)H(free) structures. This fact was explained by the former's short excited-state lifetime. We also carried out ab initio calculations using DFT-D and the M06-2X functional. The importance of the dispersion energy in stabilising peptide conformers is well reflected by our pioneer analysis using the DFT-SAPT method to explore the nature of the backbone/side-chain interactions.

Monoligand Zn(II) Complexes: Ab Initio Benchmark Calculations and Comparison with Density Functional Theory Methodologies.

A systematic theoretical study on several models of Zn(II) complexes has been carried out employing both ab initio correlated wave function and density functional methods. The performance of five different functionals namely PW91, PBE, B3LYP, MPWLYP1M, and TPSS in the prediction of metal-ligand bond distances, binding energies, and proton affinities has been assessed comparing the results to those obtained with the MP2 and CCSD(T) wave function methodologies. Several basis sets ranging from double-ζ up to quintuple-ζ quality have been used, including the recently developed all-electron correlation consistent basis sets for zinc. It is shown that all the tested functionals overestimate both the metal-ligand bond distances and the binding energies, being that the B3LYP and TPSS functionals are the ones that perform the best. An analysis of the metal-ligand interaction energy shows that induction and charge-transfer effects play a prominent role in the bonding of these systems, even for those complexes with the less polarizable ligands. This finding highlights the importance of a correct description of the polarization of the monomers' charge densities by any theoretical method which aims to be applied to the study of Zn(II) complexes.

Evaluation of the intramolecular basis set superposition error in the calculations of larger molecules: [n]helicenes and Phe-Gly-Phe tripeptide.

Correlated ab initio calculations on large systems, such as the popular MP2 (or RI-MP2) method, suffer from the intramolecular basis set superposition error (BSSE). This error is typically manifested in molecules with folded structures, characterized by intramolecular dispersion interactions. It can dramatically affect the energy differences between various conformers as well as intramolecular stabilities, and it can even impair the accuracy of the predictions of the equilibrium molecular structures. In this study, we will present two extreme cases of intramolecular BSSE, the internal stability of [n]helicene molecules and the relative energies of various conformers of phenylalanyl-glycyl-phenylalanine tripeptide (Phe-Gly-Phe), and compare the calculated data with benchmark values (experimental or high-level theoretical data). As a practical and cheap solution to the accurate treatment of the systems with large anticipated value of intramolecular BSSE, the recently developed density functional method augmented with an empirical dispersion term (DFT-D) is proposed and shown to provide very good results in both of the above described representative cases.

Benchmark RI-MP2 database of nucleic acid base trimers: performance of different density functional models for prediction of structures and binding energies.

A new database of nucleic acid base trimers has been developed that includes 141 geometries and stabilization energies obtained at the RI-MP2 level of theory with the TZVPP basis set. Compared to previously compiled biologically oriented databases, this new construct includes considerably more complicated structures; the various intermolecular interactions in the trimers are quite heterogeneous and in particular include simultaneous hydrogen bonding and stacking interactions, which is similar to the situation in actual biopolymers. Validation against these benchmark data is therefore a more demanding task for approximate models, since correct descriptions of all energy terms are unlikely to be accomplished by fortuitous cancellations of systematic errors. The density functionals TPSS (both with and without an empirical dispersion term), PWB6K, M05-2X, and BH&H, and the self-consistent charge density functional tight binding method augmented with an empirical dispersion term (SCC-DFTB-D) were assessed for their abilities accurately to compute structures and energies. The best reproduction of the BSSE corrected RI-MP2 stabilization energies was achieved by the TPSS functional (TZVPP basis set) combined with empirical dispersion; removal of the dispersion correction leads to significantly degraded performance. The M05-2X and PWB6K functionals performed very well in reproducing the RI-MP2 geometries, but showed a systematic moderate underestimation of the magnitude of base stacking interactions. The SCC-DFTB-D method predicts geometries in fair agreement with RI-MP2; given its computational efficiency it represents a good option for initial scanning of analogous biopolymeric potential energy surfaces. BH&H gives geometries of comparable quality to the other functionals but significantly overestimates interaction energies other than stacking.

Cyanides and isocyanides of first-row transition metals: molecular structure, bonding, and isomerization barriers.

Cyanides and isocyanides of first-row transition metal M(CN) (M=Sc-Zn) are investigated with quantum chemistry techniques, providing predictions for their molecular properties. A careful analysis of the competition between cyanide and isocyanide isomers along the transition series has been carried out. In agreement with the experimental observations, late transition metals (Co-Zn) clearly prefer a cyanide arrangement. On the other hand, early transition metals (Sc-Fe), with the only exception of the Cr(CN) system, favor the isocyanide isomer. The theoretical calculations predict the following unknown isocyanides, ScNC(3Delta), TiNC(4Phi), VNC(5Delta), and MnNC(7Sigma+), and agree with the experimental observation of FeNC(6Delta) and the CrCN(6Sigma+) cyanide. First-row transition metal cyanides and isocyanides are predicted to have relatively large dissociation energies with values within the range 80-101 kcal mol(-1), except Zn(CN), which has a dissociation energy around 50-55 kcal mol(-1), and low isomerization barriers. A detailed analysis of the bonding has been carried out employing the topological analysis of the charge density and an energy decomposition analysis. The role of the covalent and electrostatic contributions to the metal-ligand bonding, as well as the importance of pi bonding, are discussed.

Density-functional, density-functional tight-binding, and wave function calculations on biomolecular systems.

Recently, two computational approaches that supply a density-functional-based quantum-chemical method with an empirical term accounting for London dispersion were introduced and found use in the studies of biomolecular systems, namely, DFT-D and SCC-DFTB-D. Here, we examine the performance and usability of these combined techniques for dealing with several tasks typically occurring in the research of biomolecules. The interaction energy of small biomolecular complexes agrees very well with the reference data yielded by correlated ab initio quantum chemical methods. In real-life studies aimed at interaction energy, structure, and infrared spectra, the mentioned methods provide results in good agreement with each other and with experiment (where available). The very favorable time demands of these approaches are discussed, and for each of them, a suitable area of use is proposed on the basis of the results of our analysis.

Resolution of identity density functional theory augmented with an empirical dispersion term (RI-DFT-D): a promising tool for studying isolated small peptides.

Resolution of identity standard density functional theory augmented with a damped empirical dispersion term (RI-DFT-D) calculations have been carried out on a set of lowest energy minima of tryptophyl-glycine (Trp-Gly) and tryptophyl-glycyl-glycine (Trp-Gly-Gly) peptides. RI-DFT-D (TPSS/TZVP) results are in excellent agreement with benchmark data based on the CCSD(T) method. Experimental spectra could be assigned according to the calculated IR frequencies. Central processing unit (CPU) time requirements are only slightly higher than those needed for the DFT calculations. Consequently, RI-DFT-D theory seems to be a promising methodology for studying oligopeptides with accuracy comparable to ab initio quantum chemical calculations.

Structure of isolated tryptophyl-glycine dipeptide and tryptophyl-glycyl-glycine tripeptide: ab initio SCC-DFTB-D molecular dynamics simulations and high-level correlated ab initio quantum chemical calculations.

The tryptophyl-glycine (Trp-Gly) and tryptophyl-glycyl-glycine (Trp-Gly-Gly) peptides have been studied by means of molecular dynamic simulations combined with high-level correlated ab initio quantum chemical and statistical thermodynamic calculations. The lowest energy conformers were localized in the free energy surface. The structures of the different Trp-Gly and Trp-Gly-Gly conformers coexisting in the gas phase have been for the first time reported and their scaled theoretical IR spectra unambiguously assigned and compared with previous gas-phase experimental results. Common geometrical features have been systematically observed for the sequence Trp, Trp-Gly, and Trp-Gly-Gly. In addition, the peptide backbone of Trp-Gly-Gly has been compared with that of the previously studied Phe-Gly-Gly (Reha, D. et. al. Chem. Eur. J. 2005, 11, 6803). From the observed systematic structural behavior between these peptide analogues, it is expected that the gas-phase conformers of other similar aromatic small peptides would present equivalent geometries. The DFT methodology failed to describe the potential energy surface of the studied peptides since the London dispersion energy (not covered in DFT) plays a significant role in the stabilization of most stable conformers.