Advanced solid-state NMR methods for the elucidation of structure and dynamics of molecular, macromolecular, and supramolecular systems.

Probing proton-proton proximities in the solid state

Literature NMR data of bilirubin and related compounds and their interpretation in terms of structure, solution conformation and dynamic properties have been reviewed. 1H-spectrum assignments as well as solvent and temperature dependencies of the chemical shifts are described. Proton exchange rates, longitudinal relaxation times and nuclear Overhauser enhancements are surveyed. NMR is shown to provide knowledge on the basic structure, conformation, tautomerism, hydrogen bonding, acidity constants, segmental motion of side-chains, interconversion between enantiomers and aggregation—disaggregation of these compounds in solution.

NMR Spectroscopy of Bilirubin and its Derivatives

The success of phototherapy depends on photochemical transformations of bilirubin within light-exposed tissues. These reactions alter the structure of bilirubin in such a way that the intact molecule or fragments of it can be excreted via the kidney or liver without having to undergo further metabolic modification. So far three photochemical reactions of bilirubin have been shown to occur in vivo, and it is likely that these three together account for most of the effect of light on bilirubin metabolism in jaundiced newborns. The three reactions are photooxidation, configurational isomerization, and structural isomerization. In this presentation I shall discuss briefly some of our evidence for the occurrence of these reactions in vivo and speculate on their relative contributions to the net effect of phototherapy. Since the interpretation of the in vivo studies is very much dependent on knowledge gleaned from in vitro photochemical studies, I shall begin with a discussion of the latter.

Molecular Mechanisms of Phototherapy of Neonatal Jaundice

https://www.jbc.org/content/263/32/16669.full.pdf

Understanding bilirubin conformation and binding. Circular dichroism of human serum albumin complexes with bilirubin and its esters.

The structure of triclinic bilirubin chloroform–methanol solvate

High-order covariance matrices are used to show that the maximal determinant rule and the regression equation can be applied successfully to the phase refinement and extension of protein structures. With structure factors calculated from the atomic model of insulin, the use of an order-400 covariance matrix leads to the structure phases with an average error ΔΦ of 15°. The method has also been applied to actual data of insulin for phase refinement and for phase extension from 2.8 to 2 A.

Use of high‐order probability laws in phase refinement and extension of protein structures

Further investigation of the Karle-Hauptman determinants leads to several new relations: the DN determinant is simply related to interatomic vectors; also obtained is a probabilistic restriction on the atomic positions inside the algebraically allowed regions, as defined by von Eller. On the other hand new Gram determinants are defined and shown to be useful in relating moduli, phases and interatomic vectors. A practical application is given of fitting a stereochemically known fragment in the unit cell.

New algebraic and probabilistic relations between structure factors and direct space information

The properties of Hilbert space and group theory are used to point out the fact that the m-dimensional Laplace-Gauss law for m unknown structure factors, involving two Karle-Hauptman determinants, Δm+ 1 and Dm, can take into account full symmetry information for any space group. It is shown that the ratio (Δm+ 1/Dm) is equal to a sum of ratios of Goedkoop determinants.

Full use of symmetry in maximum‐determinant rule

A new mathematical description of phase relationships which connects different approaches, both in reciprocal and direct space, is formulated. It leads to the development of a novel algorithm for phase extension and refinement based on a probability function for atomic presence. This function, calculated from the elements of the Karle-Hauptman inverse matrix, is used in an iterative procedure. Various tests have been performed on an idealized set of calculated structure factors for an insulin model structure. The method has been applied to experimental data, Fobs, and the isomorphous phases for 2Zn insulin. An assessment of the quality of the phase refinement and calculation has been made by comparison with the crystallographically refined phases.

Y. Mauguen

Papers

The structure of triclinic bilirubin chloroform–methanol solvate

Use of high‐order probability laws in phase refinement and extension of protein structures

New algebraic and probabilistic relations between structure factors and direct space information

Full use of symmetry in maximum‐determinant rule

The extension and refinement of the 1.9 Å spacing isomorphous phases to 1.5 Å spacing in 2Zn insulin by determinantal methods