Reactivity of a rhenium hydroxo-carbonyl complex toward carbon disulfide: insights from theory

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 CS2 with [Re(OH)(CO)(3)(bipy)]. Finally, based on our mechanistic study is also possible to rationalize the formation of [Re(SC(S)OCH3)(CO)(3)(bipy)] when [Re(OCH3)(CO)(3)(bipy)] reacts with CS2 and of TpZn-OCH3 when methanol is present in the reaction of TpZn-OH with CS2

A Theoretical Study on the Reactivity of a Rhenium Hydroxo-Carbonyl Complex Towards beta-Lactams

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

Ring opening at N1-C2 bond of azetidin-2-ones by a molybdenum hydroxo-carbonyl complex: evidence from a computational study

Computations on the reaction of azetidin-2-one, N-sulfonate azetidin-2-one, and 3-formylamine-N-sulfonate azetidin-2-one with [Mo(OH)(eta(3)-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

What is the effective dielectric constant in a β-cyclodextrin cavity? Insights from Molecular Dynamics simulations and QM/MM calculations

International audienc

Understanding Regioselective Cleavage in Peptide Hydrolysis by a Palladium(II) Aqua Complex: A Theoretical Point of View

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

Taste for Chiral Guests: Investigating the Stereoselective Binding of Peptides to β-Cyclodextrins

International audienc

Computer simulation of reactions in ß-cyclodextrin molecular reactors: Transition state recognition

International audienc

Evolution of the Coordination-Sphere Symmetry in Copper(II), Nickel(II), and Zinc(II) Complexes with N,N `-Double-Armed Diaza-Crown Ethers: Experimental and Theoretical Approaches

International audienceN,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 propose

Taste for Chiral Guests: Investigating the Stereoselective Binding of Peptides to β‑Cyclodextrins

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