N,N'-Bis(triazoly)diaza[18]crown-6 and Corresponding diaza[15]crown-5 ethers were synthesized by means of click chemistry. The interaction of these ligands with Ni-II, Cu-II, and Zn-II cations were studied by UV/Vis and H-1 and C-13 NNIR spectroscopy. The solid-state structure of Ni-II and Zu(II) complexes formed by the diaza[18]crown-6 ligand were determined by means of X-ray crystallography. The Ni-II complex is centrosyrnmetric; the geometry around the metal ion is slightly distorted octahedral whereby the equatorial sites were occupied by four N atoms, and the axial positions by two O atoms that come from the crown moiety. For the Zn" diaza[18]crown-6 complex, an irregular octahedral coordination was observed whereby the metal ion is asymmetrically placed in the macrocyclic cavity. The equatorial plane is occupied by two N and two O atoms of the crown moiety, and to N atoms of the triazolyl motifs on the pendant arms occupy the axial positions. The diamagnetic character of the Zn" ion allows its structural study in solution by NNIR spectroscopy. A dynamic beh avior was observed at room Lem- perEaure, which coriesporids to the displacement. ion between the bond end and the nonbond end of the macrocycle. This movement results in an S4-symmetrical structure in solution. Quantum chemical calculations at the DFT level have allowed us to interpret the experimental results observed in the solid state for the symmetry of the complexes in terms of covalent and noncovalent interactions, which favor the centrosymmetric and irre. gular octahedral coordination modes, respectively. Only the structure of the Cu-II complex with N,N'-bis(triazolyl)diazal[5]crown-5 ligand has been investigated in the solid state, for which a pentagonal bipyramidal coordination sphere was observed. This coordination geometry was confirmed in solution in MeCN by UV/Vis spectroscopy, and also for the Zn-II complex by NMR spectroscopy. In the case of the Ni-II complex, a structural modification was suggested in solution in MeCN based on the UV/Vis spectrum. The rearrangement of heptadentate coordination to hexadentate is proposed

Digital data have become a torrent engulfing every area of business, science and engineering disciplines. In the age of Big Data, deriving values and insights from large amounts of data using rich analytics becomes an important differentiating capability for competitiveness, success and leadership in every field. Scientists and engineers of many different domains are increasingly clamouring for mechanisms to manage and analyse the massive quantities of information now available in order to obtain new answers and extract from it maximum value. Computational modelling and simulation is the central technology to numerous of these domains. Molecular Dynamics (MD) is a computational simulation technique that describes the physical forces and movements of interacting microscopic elements such atoms and molecules. MD has important applications in the fields of chemistry, biotechnology, pharmaceutical industry, energy, climate or materials science, among others. Advanced MD algorithms include not only Molecular Mechanics (MM), but also Quantum Mechanics (QM) approaches, raising important big data challenges still to be sorted out. MD simulations perform an iterative process generating large amounts of data in streaming. Current software technology is far from being able to manage, analyze and visualize the extremely large and complex data sets generated by important molecular processes. This paper analyzes the current big data limits in the Computational Chemistry field, especially in the MD processes. To overcome these challenging situations, this work provide guidance for future research including advances in scalable algorithms for data analysis, dynamic query technology, data models and storage strategies, parallel executions, I/O optimization, and interactive visual exploration and analysis of MD data.

Obtaining compounds of diastereomeric purity is extremely important in the field of biological and pharmaceutical industry, where amino acids and peptides are widely employed. In this work, we theoretically investigate the possibility of chiral separation of peptides by β-cyclodextrins (β-CDs), providing a description of the associated interaction mechanisms by means of molecular dynamics (MD) simulations. The formation of host/guest complexes by including a model peptide in the macrocycle cavity is analyzed and discussed. We consider the terminally blocked phenylalanine dipeptide (Ace-Phe-Nme), in the L- and D-configurations, to be involved in the host/guest recognition process. The CD-peptide free energies of binding for the two enantiomers are evaluated through a combined approach that assumes: (1) extracting a set of independent molecular structures from the MD simulation, (2) evaluating the interaction energies for the host/guest complexes by hybrid quantum mechanics/molecular mechanics (QM/MM) calculations carried out on each structure, for which we also compute, (3) the solvation energies through the Poisson-Boltzmann surface area method. We find that chiral discrimination by the CD macrocycle is of the order of 1 kcal/mol, which is comparable to experimental data for similar systems. According to our results, the Ace-(D)Phe-Nme isomer leads to a more stable complex with a β-CD compared to the Ace-(L)Phe-Nme isomer. Nevertheless, we show that the chiral selectivity of β-CDs may strongly depend on the secondary structure of larger peptides. Although the free energy differences are relatively small, the predicted selectivities can be rationalized in terms of host/guest hydrogen bonds and hydration effects. Indeed, the two enantiomers display different interaction modes with the cyclodextrin macrocavity and different mobility within the cavity. This finding suggests a new interpretation for the interactions that play a key role in chiral recognition, which may be exploited to design more efficient and selective chiral separations of peptides.

We report a theoretical study on polarization effects induced by the environment on a solute placed inside a β-cyclodextrin macrocycle in aqueous solution. Calculations are carried out for a simple guest molecule p-nitrochlorobenzene using a combined Molecular Dynamics and QM/MM approach. The results have allowed us to derive an effective dielectric constant for the CD-water environment in the range 3–8 that agrees well with several experimental estimations reported in the literature. The investigation emphasizes the fact that the polarization effect is practically the same for the two possible relative orientations of the host–guest complex. For substrates able to form strong specific interactions with either the CD or the water solvent, the medium effects could be different for different orientations, however. In addition, in those cases, specific medium effect would add to the purely dielectric one. This last fact can explain why experimental studies have led to a very large range of values for the effective dielectric constant of β-CDs cavities.

Peptide-cyclodextrin and protein-cyclodextrin host-guest complexes are becoming more and more important for industrial applications, in particular in the fields of pharmaceutical and food chemistry. They have already deserved many experimental investigations although the effect of complex formation in terms of peptide (or protein) structure is not well-known yet. Theoretical calculations represent a unique tool to analyze such effects, and with this aim we have carried out in the present investigation molecular dynamics simulations and combined quantum mechanics-molecular mechanics calculations. We have studied complexes formed between the model Ace-Phe-Nme peptide and the β-cyclodextrin (β-CD) macromolecule, and our analysis focuses on the following points: (1) how is the peptide structure modified in going from bulk water to CD environment (backbone torsion angles), (2) which are the main peptide-CD interactions, in particular in terms of hydrogen bonds, (3) which relative peptide-CD orientation is preferred and which are the structural and energetic differences between them, and (4) how the electronic properties of the peptide changes under complex formation. Overall, our calculations show that in the most stable configuration, the backbone chain lies in the narrow rim of the CD. Strong hydrogen bonds form between the H atoms of the peptidic NH groups and oxygen atoms of the secondary OH groups in the CD. These and other (weaker) hydrogen bonds formed by the carbonyl groups reduce considerably the flexibility of the peptide structure, compared to bulk water, and produce a marked increase of the local dipole moment by favoring configurations in which the two C═O bonds point toward the same direction. This effect might have important consequences in terms of the peptide secondary structure, although this hypothesis needs to be tested using larger peptide models.

Hydrolytic: cleavage of the oligopeptides Ace-Ala-Lys-Tyr-Gly similar to Gly-Met-Ala-Ala-Arg-Ala and Ace-Lys-Gly-Gly-Ala-Gly similar to Pro-Met-Ala-Ala-Arg-Gly by [Pd(H2O)(4)](2+) was theoretically investigated by using molecular dynamics simulations and quantum mechanical calculations. The Pd anchorage to the peptide sequence is crucial to provoke the cleavage of the second bond upstream from the anchored methionine. For both cases, the most favorable reaction mechanism is a three-step route. The first step coincides with the experimental suggestion found for the Gly similar to Pro-Met sequence on a cleavage caused by an external attack of a water molecule to a complex in trans conformation of the scissile Gly similar to Gly and Gly similar to Pro peptide bonds. However, our results uncover the important role played by the presence of a Pd-coordinated water molecule, which simultaneously interacts with the carbonyl oxygen atom of the Gly amino acid in the Gly similar to Gly and Gly similar to Pro bonds. In accordance with experimental facts, the rise of the hydrolysis reaction rate when the Pro amino acid is located in the scissile peptide bond was also corroborated. The findings obtained at a molecular level from the present computations not only are relevant to rationalize the previously reported experiments but also could be of importance in designing new Pd(II) complexes for the regioselective cleavage of peptides and proteins.

Cyclodextrins have attracted much interest in recent years because of their potential use as molecular reactors allowing organic reactions in aqueous solution. To better understand their effect on reaction mechanisms, we have carried out a computational study of a prototypical process (neutral ester hydrolysis) in a beta-cyclodextrin (beta-CD). Two models have been used for the reactor. The first and simpler one assumes that the medium can be described by a polarizable dielectric continuum. The second one takes into account the discrete nature of the beta-CD and water molecules thanks to a computational approach that combines the use of Quantum Mechanics, Molecular Mechanics and Molecular Dynamics techniques. We focus on neutral pH processes for which either acceleration or inhibition has experimentally been observed depending on ester derivatives. Our calculations rationalize such observations by showing that the two reaction mechanisms usually invoked for hydrolysis, stepwise (involving two transitions states with formation of a -C(OH)(2)OR tetrahedral intermediate) and concerted, undergo opposite effects in the beta-CD environment. The results highlight the role played by molecular shape recognition. Thus, in spite of a higher polarity exhibited by the three transition states with respect to the reactants, the interactions with the beta-CD cavity may either increase or decrease the activation barrier due to different 3D-arrangements of the chemical structures.

The B3LYP density functional theory methodology in conjunction with the 6-31G(d,p) basis set has been used to characterize triply N-confused meso -tetraphenylporphyrins. According to our computations, there is no a direct correlation between stability and aromaticity as already found for non-substituted confused porphyrins. The inclusion of these substituents in the calculations provokes a decrease of the planarity and aromaticity of these macrocycles along with a notable rise of their relative stability with respect to the non-substituted case. Steric repulsions, both among phenyl rings and β atoms in the pyrrolic rings, and among H atoms in the core of the macrocycles, dominate over aromaticity in the establishment of the most stable conformation of each isomer.

The reaction mechanism on the formation of the hydrosulfido complex [Re(SH)(CO)(3)(bipy)] via the reaction of [Re(OH)(CO)(3)(bipy)] with carbon disulfide was theoretically investigated at the B3LYP/6-31+G(d,p) (LANL2DZ+f for Re) level of theory taking into account bulk solvent effects by using the PCM-UAHF continuum model. The energetics of the process was also analyzed by means of single-point energy calculations by replacing the B3LYP functional by the B3PW91, M05, TPSS and TPSSh ones. The most favored mechanistic routes obtained by us uncover all the molecular rearrangements involved in the reactive process, thus allowing the enriching of the experimental mechanistic proposal. Besides, our findings permit to explain the assignment of the solution color change to the formation of [Re(SH)(CO)(3)(bipy)] when mixed CS(2) with [Re(OH)(CO)(3)(bipy)]. Finally, based on our mechanistic study is also possible to rationalize the formation of [Re(SC(S)OCH(3))(CO)(3)(bipy)] when [Re(OCH(3))(CO)(3)(bipy)] reacts with CS(2) and of TpZn-OCH(3) when methanol is present in the reaction of TpZn-OH with CS(2).

The mechanism of the reaction between the complex [Re(OH)(CO)(3)(N2C2H4)] and azetidin-2-one or 3-formylamino-N-sulf onatoazetidin-2-one was investigated by using the B3LYP density functional theory methodology in conjunction with the PCM-UAHF model to take into account solvent effects. According to our calculations, the rate-determining energy barrier for the azetidin-2-one case of 38.8 kcal mol(-1), becomes 25.7 kcal mol(-1) in the case of the 3-formylamino-N-sulf onatoazetidin-2-one species. The presence of the sulfonato group is crucial for the cleavage of the P-lactam N1-C2 bond by the Re complex thanks to the interaction of the sulfonato group with the hydroxy and bidentate ligands of the complex. This could be of interest for the synthesis of beta-amino acids and their derivatives from beta-lactams under mild conditions and in solvents of low polarity promoted by organometallic complexes. (C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

Computations on the reaction of azetidin-2-one, N-sulfonate azetidin-2-one, and 3-formylamine-N-sulfonate azetidin-2-one with [Mo(OH)(eta3-C3H5)(CO)2(N2C2H4)] were performed at the B3LYP/6-31+G(d,p) (LANL2DZ for Mo augmented by f polarization functions with exponents 1.043) taking into account solvent effects by means of the PCM-UAHF model. According to our calculations, the rate-determining energy barrier for the azetidin-2-one case, 38.0 kcal mol(-1), becomes 28.8 and 26.1 kcal mol(-1) for the N-sulfonate azetidin-2-one and 3-formylamine-N-sulfonate azetidin-2-one ones, respectively. The presence of the sulfonate group is crucial to cleave the beta-lactam N1-C2 bond by the Mo complex thanks to the interaction of the sulfonate group with the hydroxyl and bidentate ligands of the complex. This could be of interest for the synthesis of beta-amino acids and their derivatives from beta-lactams in mild conditions and low polarity solvents promoted by organometallic complexes.

The reaction of [Mo(OH)(eta(3)-C3H5)(CO)(2)(N2C2H4)] and [Re(OH)(CO)(3)(N2C2H4)] with phenyl acetate to give phenol and [Mo(OAc)(eta(3)-C3H5)(CO)(2)(N2C2H4)] and [Re(OAc)(CO)(3)(N2C2H4)L respectively, was investigated by using the B3LYP density functional theory methodology in conjunction with the PCMUAHF model to take into account solvent effects. For both complexes, the most favorable reaction mechanism is concerted and takes place, for the first time in the metal-promoted ester hydrolysis, through the addition of the complex O-H bond to the ester single C-O bond. The larger reactivity of the Mo complex experimentally found is explained in terms of the interaction detected in the rate-determining TS between one of the lone pairs of the oxygen atom bearing the phenyl group and the two pi-antibonding C-N of the bidentate ligand. Due to the existence of a conformational equilibrium for the Mo complex, its reaction with phenyl acetate can evolve through a rate-determining TS 2.4 kcal mol(-1) lower in relative energy than that found for the Re case, thus explaining the ratio between both periods of experimental reaction time.

The cleavage of the amide bond of formamide in dichloromethane by attack of the hydroxyl ligand in [Mo(OH)(η3-C3H5)(CO)2(N2C2H4)] and [Re(OH)(CO)3(N2C2H4)] complexes was theoretically investigated at the B3LYP/6-31+G(d) level (LANL2DZ for Mo and Re atoms). The effect of CH2Cl2 as solvent was evaluated by the PCM-UAHF method. According to our theoretical results the more favorable mechanisms for these reactions are concerted. The energy barriers obtained by us (54.6kcalmol−1 for [Mo(OH)(η3-C3H5)(CO)2(N2C2H4)] and 51.9kcalmol−1 for [Re(OH)(CO)3(N2C2H4)]) are higher than those found for the neutral hydrolysis of formamide in water (about 44–46kcalmol−1). In contrast with water solvent, the effect of bulk CH2Cl2 is quite important increasing the barriers of these two concerted processes by about 2 and 6kcalmol −1, respectively, and making more favorable the concerted mechanism in solution in the case of the Mo complex.