Alain Borel

ChemCalc: a building block for tomorrow’s chemical infrastructure

Web services, as an aspect of cloud computing, are becoming an important part of the general IT infrastructure, and scientific computing is no exception to this trend. We propose a simple approach to develop chemical Web services, through which servers could expose the essential data manipulation functionality that students and researchers need for chemical calculations. These services return their results as JSON (JavaScript Object Notation) objects, which facilitates their use for Web applications. The ChemCalc project http://www.chemcalc.org demonstrates this approach: we present three Web services related with mass spectrometry, namely isotopic distribution simulation, peptide fragmentation simulation, and molecular formula determination. We also developed a complete Web application based on these three Web services, taking advantage of modern HTML5 and JavaScript libraries (ChemDoodle and jQuery).

A general approach to the electronic spin relaxation of Gd(III) complexes in solutions. Monte Carlo simulations beyond the Redfield limit

The time correlation functions of the electronic spin components of a metal ion without orbital degeneracy in solution are computed. The approach is based on the numerical solution of the time-dependent Schrodinger equation for a stochastic perturbing Hamiltonian which is simulated by a Monte Carlo algorithm using discrete time steps. The perturbing Hamiltonian is quite general, including the superposition of both the static mean crystal field contribution in the molecular frame and the usual transient ligand field term. The Hamiltonian of the static crystal field can involve the terms of all orders, which are invariant under the local group of the average geometry of the complex. In the laboratory frame, the random rotation of the complex is the only source of modulation of this Hamiltonian, whereas an additional Ornstein–Uhlenbeck process is needed to describe the time fluctuations of the Hamiltonian of the transient crystal field. A numerical procedure for computing the electronic paramagnetic resonanc...

Gd(III) based MRI contrast agents: improved physical meaning in a combined analysis of EPR and NMR data?

A new global analysis of EPR, 17O NMR relaxation and chemical shift and 1H NMRD profiles with physically meaningful parameters for [Gd(DOTA)(H2O)]− and for [Gd(DTPA)(H2O)]2− in aqueous solution is presented (DOTA=1,4,7,10-tetraaza-1,4,7,10-tetrakis(carboxymethyl)-cyclododecane; DTPA=diethylenetriamine-N,N,N′,N″,N″-pentaacetic acid). The recent developments of an improved EPR relaxation theory, the inclusion of the internal motion of the bound water molecule are the principal modifications. Furthermore the better knowledge of the quadrupolar coupling constant of the bound water molecule, the neglect of the outer-sphere contribution to the chemical shift and the consideration of different isomers for the DOTA complex allowed for an improved analysis. The water exchange and parameters of rotational motion are only slightly changed. Comparison of the contributions of static zero-field-splitting shows that a more symmetric environment of the Gd(III) ion should lead to slower electron spin relaxation, a feature which can become important if all other parameters (rotational correlation time and water exchange rate) are optimised. In the actual stage the improved combined analysis of Gd(III) poly(amino carboxylate) is limited by the approximations of Redfield’s relaxation theory, i.e., very low frequency NMRD-data and slowly tumbling complexes cannot be analysed with the method presented.

Towards the Rational Design of MRI Contrast Agents: Electron Spin Relaxation Is Largely Unaffected by the Coordination Geometry of Gadolinium(III)-DOTA-Type Complexes

Electron-spin relaxation is one of the determining factors in the efficacy of MRI contrast agents. Of all the parameters involved in determining relaxivity it remains the least well understood, particularly as it relates to the structure of the complex. One of the reasons for the poor understanding of electron-spin relaxation is that it is closely related to the ligand-field parameters of the Gd(3+) ion that forms the basis of MRI contrast agents and these complexes generally exhibit a structural isomerism that inherently complicates the study of electron spin relaxation. We have recently shown that two DOTA-type ligands could be synthesised that, when coordinated to Gd(3+), would adopt well defined coordination geometries and are not subject to the problems of intramolecular motion of other complexes. The EPR properties of these two chelates were studied and the results examined with theory to probe their electron-spin relaxation properties.

Stochastic Liouville equation treatment of the electron paramagnetic resonance line shape of an S-state ion in solution.

The current approaches used for the analysis of electron paramagnetic resonance spectra of Gd3+ complexes suffer from a number of drawbacks. Even the elaborate model of [Rast et al., J. Chem. Phys. 113, 8724 (2000)] where the electron spin relaxation is explained by the modulation of the zero-field splitting (ZFS), by molecular tumbling (the so called static contribution), and deformations (transient contribution), is only readily applicable within the validity range of the Redfield theory [Advances in Magnetic Resonance, edited by J.-S. Waugh (Academic, New York, 1965), Vol. 1, p. 1], that is, when the ZFS is small compared to the Zeeman energy and the rotational and vibrational modulations are fast compared to the relaxation time. Spin labels (nitroxides and transition metal complexes) have been studied for years in systems that violate these conditions. The theoretical framework commonly used in such studies is the stochastic Liouville equation (SLE). The authors shall show how the physical model of Rast et al. can be cast into the SLE formalism, paying special attention to the specific problems introduced by the [Uhlenbeck and Ornstein, Phys. Rev. 36, 823 (1930)] process used to model the transient ZFS. The resulting equations are very general and valid for arbitrary correlation times, magnetic field strength, electron spin S, or symmetry. The authors demonstrate the equivalence of the SLE approach with the Redfield approximation for two well-known Gd3+ complexes.

Molecular Dynamics of Gd(III) Complexes in Aqueous Solution by HF EPR

The study of electron spin relaxation in aqueous Gd(III) complexes is the source of new insights into the physics and chemistry of magnetic resonance imaging (MRI) contrast agents. The coupling of the seven unpaired electrons of the Gd(III) ion with the surrounding water protons observed in MRI is the basis of the contrast agent effectiveness. Therefore, understanding the behavior of the electron spin system can provide valuable information for the development of new compounds. The availability of high frequency electron paramagnetic resonance (HF EPR) spectrometers is vital for complete relaxation studies, and played an important role in improving our knowledge of Gd(III) electron spin relaxation in the last few years. Variable temperature HF EPR has been an invaluable tool to improve our understanding of the underlying relaxation mechanisms.

Molecular dynamics simulation of Gadolinium(III) complexes in aqueous solution

Note: Abstract of a lecture given at the 10th International Conference on Bioinorganic Chemistry (Florence, Florence, August 26 – 31, 2001) Reference LCIB-ARTICLE-2006-020doi:10.1016/S0162-0134(01)00251-3 Record created on 2006-11-09, modified on 2017-05-12

Molecular dynamics simulations of the internal mobility of Gd3+-based MRI contrast agents: Consequences for water proton relaxivity

The increasing use of contrast agents in magnetic resonance imaging (MRI) for medical diagnosis is due to the ability, called relaxivity, of these paramagnetic compounds to accelerate the relaxation of the surrounding water proton spins. A new classical force field for molecular dynamics simulations of Gd3+ polyaminocarboxylates has recently been published, which allows the study of the chelate internal mobility. We present two selected examples where such motions can affect relaxivity. Knowing the relationship between the bound water proton and oxygen mobility is important for the combined analysis of multinuclear NMR studies, and we show that they differ significantly. Next, we observe symmetry changes over time in the Gd3+ coordination polyhedron of the acyclic complexes. We propose that such rearrangements can play a role in the electron spin relaxation of Gd3+ chelates, an important result considering the uncertainty still attached to this particular factor.