546 research outputs found
Evaluation of Water Exchange Kinetics on [Ln(AAZTAPh–NO2)(H2O)q]x Complexes Using Proton Nuclear Magnetic Resonance
No full textWater exchange kinetics on [Ln(AAZTAPh–NO2)(H2O)q]− (Ln = Gd3+, Dy3+, or Tm3+) were determined by 1H nuclear magnetic resonance (NMR) measurements. The number of inner-sphere water molecules was found to change from two to one when going from Dy3+ to Tm3+. The calculated water exchange rate constants obtained by variable-temperature proton transverse relaxation rates are 3.9 × 106, 0.46 × 106, and 0.014 × 106 s–1 at 298 K for Gd3+, Dy3+, and Tm3+, respectively. Variable-pressure measurements were used to assess the water exchange mechanism. The results indicate an associative and dissociative interchange mechanism for Gd3+ and Dy3+ complexes with ΔV⧧ values of −1.4 and 1.9 cm3 mol–1, respectively. An associative activation mode (Ia or A mechanism) was obtained for the Tm3+ complex (ΔV⧧ = −5.6 cm3 mol–1). Moreover, [Dy(AAZTAPh–NO2)(H2O)2]− with a very high transverse relaxivity value was found as a potential candidate for negative contrast agents for high-field imaging applications.LCI
Structural and dynamic parameters obtained from (17)O NMR, EPR, and NMRD studies of monomeric and dimeric Gd(3)+ complexes of interest in magnetic resonance imaging: an integrated and theoretically self-consistent approach(1)
No full textD. Hugh Powell, Orla M. Ni Dhubhghaill, Dirk Pubanz, Lothar Helm, Yakob S. Lebedev, Willi Schlaepfer, and André E. Merbac
Relevance of the ligand exchange rate and mechanism of fac-[(CO)3M(H2O)3]+ (M = Mn, Tc, Re) complexes for new radiopharmaceuticals
No full textCopyright © 2006 American Chemical SocietyPascal V. Grundler, Lothar Helm, Roger Alberto, and André E. Merbac
Water-Exchange Study Revealed Unexpected Substitution Behavior of [(CO)2(NO)Re(H2O)3]2+ in Aqueous Media
No full textCopyright © 2006 American Chemical SocietyMarie-Line Lehaire, Pascal V. Grundler, Stefan Steinhauser, Niklaus Marti, Lothar Helm, Kaspar Hegetschweiler, Roger Schibli, and André E. Merbac
Methodological aspects of the SAVE data set
No full textThis paper describes the general design of the SAVE survey: the design of the questionnaire, inter-viewer and interviewee motivation, and the sampling designs of the various subsamples collected in 2001 and 2003. It discusses the representativeness of the data, explains the construction of weights, and provides probit regressions to analyse potential selectivity problems. The paper finishes by discussing implications for the use of the SAVE data in various estimation procedures.
Kinetic studies on the first dihydrogen aquacomplex, [Ru(H(2))(H(2)O)(5)](2+): Formation under H(2) pressure and catalytic H/D isotope exchange in water
No full textCopyright © 2005 Elsevier B.V. All rights reserved.Pascal V. Grundler, Oleg V. Yazyev, Nicolas Aebischer, Lothar Helm, Gábor Laurenczy and André E. Merbac
Study of fast exchanging processes by NMR Spectroscopy
No full textNuclear magnetic resonance (NMR) spectroscopy is one of the most powerful and informative methods to probe molecular dynamics. Specifically, chemical exchange is an important phenomenon and one of the earliest and most vigorously investigated in NMR spectroscopy. Its effects can be observed in many NMR spectra; lines in a spectrum are broadened or averaged because the nuclei are exchanging magnetic environments. A wide variety of experimental methods exists to determine exchange rates of protons that hop between amino acids and water in the slow or intermediate exchange regime. However, so far there is a lack of methods to investigate hydrogen exchange in the fast exchange regime. In this thesis, we focus on the determination of very fast chemical exchange rates from the effects of scalar relaxation on a coupled nucleus. We quantify the effects of scalar relaxation caused by exchanging hydrogens, by detecting the decay of a 15N coherence under a multiple-refocusing Carr-Purcell-Meiboom-Gill (CPMG) pulse train in the presence or absence of hydrogen decoupling. In particular, we have adapted to the case of deuterium a method that was originally designed to study the exchange rate of the indole proton of tryptophan in water as a function of pH and temperature. We will present the exchange rates of the indole deuterium in tryptophan with solvent heavy water. After that, the proton exchanges rates have been compared with the deuterium exchange rates in order to describe the kinetic isotope effect. In a similar manner, we have quantified the proton exchange rates in pure water by using multiple refocusing of transverse 17O magnetization as a function of pH and temperature. Such measurements are widely used to obtain valuable information about molecular dynamics and structure of proteins, protein complexes and nucleic acids. The knowledge of the kinetic isotope effect may contribute to the characterization of reaction mechanisms and other dynamic parameters that can give insight into the stability of hydrogen bonded secondary structures in biomolecules. This information could form a foundation for a more thorough theoretical or modeling development of a number of long and outstanding fundamental questions. In the second part of the thesis, we combine fast exchange with dissolution dynamic nuclear polarization (D-DNP) to study intrinsically disordered proteins (IDPs). IDPs constitute a very large and functionally important class of proteins that lack stable secondary and tertiary structures. As a consequence of the broad dynamics and flexibility of IDPs, and specially under physiological conditions, the NMR spectra of IDPs typically show a strong signal overlap and broadening due to proton exchange. We present a method to overcome these limitations by means of hyperpolarized HDO produced by D-DNP. We could study the effects of conformational adaptations in Osteopontin (OPN), a metastasis- associated intrinsically disordered protein (IDP) by chemical exchange. The magnetization from hyperpolarized water is transferred to the rapidly exchanging protons of the solvent-exposed residues of the protein. The exchange with hyperpolarized water boosts the signals of fast exchanging residues above the detection limits. This allows one to follow individual resonances and draw conclusions regarding conformational adaptations due to ligand binding under physiological conditions. Thus, with our approach, exchange with the solvent is turned into an advantageLCI
Synthesis and MRI properties characterization of Gd3(Mes(DO3A)3): from spring-roll to pancake relaxivity
No full textSCGCGR-53 627; EPFL - SB - ISIC - LCIB. Consultable sur demande à la Bibliothèque de l'EPFL / Offered in consultation at the EPFL library
Water exchange studies of lanthanide complexes and aqua ions
No full textComplexes of lanthanide (III) ions have been used in structural studies of biomolecules and as contrast agents (CA). Clinically approved CAs have only one water molecule in their first coordination sphere. Structure and water exchange rate of these complexes have been very well studied, however, water exchange kinetics of lanthanide complexes with two coordinated water molecules have not been investigated widely. In this regard, in the present work, a comprehensive study of water exchange kinetics of selected Ln3+ complexes with different ligands having two inner-sphere water molecules was conducted. In chapter III, selected lanthanide complexes of DO3A and DTTA-Me as representatives for macrocyclic and acyclic ligands have been studied by 17O NMR spectroscopy and 1H nuclear magnetic relaxation dispersion (NMRD). Water exchange rate constants measured on both complexes show a maximum at dysprosium and are much faster on DTTA-Me complexes than on the DO3A complexes. A change in water exchange mechanism is detected depending on both lanthanide and ligand structure. When analyzing the water exchange rates of [Ln(L)(H2O)2]x complexes, a unique rate constant for the exchange of the two water molecules was considered, however, the individual rate constants can be either very similar or very different. In order to investigate this, in chapter IV, the replacement of coordinated water molecule(s) in [Gd(DTTA-Me)(H2O)2]- by fluoride anions using multinuclear NMR spectroscopy was studied. Variable pressure 17O NMR measurements were also conducted for mechanistic assignment of the exchange reactions. It was found that fluoride binding facilitate the departure of the coordinated water molecule following a dissociative mechanism and accordingly cause a marked acceleration of the water exchange. In chapter V, the water exchange properties of lanthanide complexes of AAZTAPh-NO2 ligand was studied by 1H NMR spectroscopy. Water exchange rate constants were found to change more than two orders of magnitude along the series. Moreover, [Dy(AAZTAPh-NO2)(H2O)2]- was found to potentially be a very effective negative contrast agent for high magnetic fields imaging applications. Chapter VI is dedicated to the water exchange kinetics of selected lanthanide perchlorate and chloride aqua ions at different concentrations of 0.5 m to 2 m in order to establish the extent to which the nature of the counter-ion and the concentration of the Ln3+ change the rate and mechanism of the water exchange. Our results measured on neodymium ion are the first direct experimental proof for the maximum of water exchange rate constant along the lanthanide series as well as the change of the mechanism for water exchange from a dissociative mechanism for aqua ions of the early lanthanides to an associative mechanism for those of the late lanthanides.LCI
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