Hyaluronic acid: molecular conformations and interactions in the orthorhombic and tetragonal forms containing sinuous chains.

The conformation, packing and probable mode of cation binding have been determined for compact potassium hyaluronate chains (average rise per disaccharide h = 0.89 nm) organized in an orthorhombic unit cell (a = 1.173 nm, b = 0.925 nm, c = 3.542 nm). The space group symmetry is P2(1)2(1)2(1) and the unit cell contains two antiparallel polysaccharide chains that are disturbed 4(3) helices. Each chain is stabilized intramolecularly by four hydrogen bonds and between adjacent antiparallel chains there are two intermolecular hydrogen bonds per crystallographic tetrasaccharide repeat. Fourier difference synthesis revealed two potassium ions and two water molecules in each asymmetric unit. Both potassium ions show octahedral co-ordination geometries and link adjacent antiparallel polysaccharide chains. The water molecules provide further intermolecular association through water bridges. A comparison of this potassium hyaluronate structure with the orthorhombic and tetragonal sodium hyaluronate structures containing similar compact hyaluronate chains revealed that the apparently isomorphous orthorhombic sodium and potassium salts did not have the same packing arrangements. The relative orientations of the sinuous hyaluronate chains in the sodium and potassium salts are about 90 degrees apart. The locations of the cations and hence the coordination schemes of K+ and Na+ are therefore very different. These analyses have delineated, for the first time, how hyaluronate chains can respond differentially to two different monovalent cations.