Lee Fielding

Bio: Lee Fielding is an academic researcher from AkzoNobel. The author has contributed to research in topics: Carbon-13 NMR & Rocuronium Bromide. The author has an hindex of 8, co-authored 12 publications receiving 1090 citations.

Determination of protein-ligand binding affinity by NMR: observations from serum albumin model systems.

Abstract: The usefulness of bovine serum albumin (BSA) as a model protein for testing NMR methods for the study of protein-ligand interactions is discussed. Isothermal titration calorimetry established the binding affinity and stoichiometry of the specific binding site for L-tryptophan, D-tryptophan, naproxen, ibuprofen, salicylic acid and warfarin. The binding affinities of the same ligands determined by NMR methods are universally weaker (larger KD). This is because the NMR methods are susceptible to interference from additional non-specific binding. The L-tryptophan-BSA and naproxen-BSA systems were the best behaved model systems.

NMR diffusion spectroscopy as a measure of host-guest complex association constants and as a probe of complex size.

Abstract: The complexes of cyclohexylacetic acid and cholic acid with β-cyclodextrin were studied by NMR diffusion coefficient measurements. The diffusion coefficient of the 1:1 cyclohexylacetic acid/β-cyclodextrin complex, Ka = 1800 ± 100 M-1, is slightly slower (3.23 ± 0.07 × 10-6 cm2 s-1) than that of β-cyclodextrin (3.29 ± 0.07 × 10-6 cm2 s-1). The diffusion coefficient of the 1:1 cholic acid/β-cyclodextrin complex, Ka = 5900 ± 800 M-1, is significantly slower (2.93 ± 0.07 × 10-6 cm2 s-1) than that of β-cyclodextrin. The results indicate that caution should be exercised when studying host−guest complexation by the so-called ‘single point' technique. A novel data treatment is introduced which takes into account the diffusion behavior of all of the species when determining Ka. Experimentally determined diffusion coefficients of complexes are also a useful probe of the size of host−guest complexes.

NMR diffusion coefficient study of steroid–cyclodextrin inclusion complexes

Abstract: The complexes formed by the steroid rocuronium bromide with four different cyclodextrins (β-cyclodextrin, γ-cyclodextrin, Org 26054 and Org 25969) were investigated. The diffusion coefficients of the steroid–cyclodextrin complexes were 6–15% lower than those of the native cyclodextrins, consistent with a 1 : 1 stoichiometry for all of the complexes. Copyright © 2002 John Wiley & Sons, Ltd.

Diffusion NMR Spectroscopy in Supramolecular and Combinatorial Chemistry: An Old Parameter—New Insights

Abstract: Intermolecular interactions in solution play an important role in molecular recognition, which lies at the heart of supramolecular and combinatorial chemistry. Diffusion NMR spectroscopy gives information over such interactions and has become the method of choice for simultaneously measuring diffusion coefficients of multicomponent systems. The diffusion coefficient reflects the effective size and shape of a molecular species. Applications of this technique include the estimation of association constants and mapping the intermolecular interactions in multicomponent systems as well as investigating aggregation, ion pairing, encapsulation, and the size and structure of labile systems. Diffusion NMR spectroscopy can also be used to virtually separate mixtures and screen for specific ligands of different receptors, and may assist in finding lead compounds.

Synthetic and Mechanistic Studies of Pd-Catalyzed C−H Arylation with Diaryliodonium Salts: Evidence for a Bimetallic High Oxidation State Pd Intermediate

Abstract: This contribution describes the substrate scope and mechanism of Pd-catalyzed ligand-directed C-H arylation with diaryliodonium salts. This transformation was applied to the synthesis of a variety of different biaryl products, using directing groups including pyridines, quinolines, pyrrolidinones, and oxazolidinones. Electronically and sterically diverse aryl groups (Ar) were transferred in high yield using iodine(III) reagents of general structure [Mes-I-Ar]BF(4). Mechanistic investigations have been conducted that establish the kinetic order of the catalytic reaction in each component, determine the resting state of the catalyst and the iodine(III) reagent, quantify the electronic influence of the arylating reagent on the reaction rate, and establish the intra- and intermolecular 1 degree H/D kinetic isotope effect. On the basis of these studies, this transformation is proposed to proceed via turnover-limiting oxidation of the Pd dimer [Pd(N~C)(OAc)](2) (N~C = 3-methyl-2-phenylpyridine) by [Mes-I-Ph]BF(4). This mechanism implicates a bimetallic high oxidation state Pd species as a key catalytic intermediate. The significance of this and other aspects of the proposed mechanism are discussed in detail.

Method of Continuous Variations: Applications of Job Plots to the Study of Molecular Associations in Organometallic Chemistry[**]

Abstract: Applications of the method of continuous variations (MCV or the Method of Job) to problems of interest to organometallic chemists are described. MCV provides qualitative and quantitative insights into the stoichiometries underlying association of m molecules of A and n molecules of B to form AmBn . Applications to complex ensembles probe associations that form metal clusters and aggregates. Job plots in which reaction rates are monitored provide relative stoichiometries in rate-limiting transition structures. In a specialized variant, ligand- or solvent-dependent reaction rates are dissected into contributions in both the ground states and transition states, which affords insights into the full reaction coordinate from a single Job plot. Gaps in the literature are identified and critiqued.