Competing Effects of Hydration and Cation Complexation in Single-Chain Alginate

Abstract

Alginic acid, a naturally occurring anionic polyelectrolyte, forms strong physically cross-linked hydrogels in the presence of metal cations. The latter engage in electrostatic interactions that compete with intra- and intermolecular hydrogen bonds, determining the gel structure and properties of the system in aqueous media. In this study, we use all-atom molecular dynamics simulations to systematically analyze the interactions between alginic acid chains and Na+ and Ca2+ counterions. The formed alginates originate from the competition of intramolecular hydrogen bonding and water coordination around the polyelectrolyte. In contrast to the established interpretation, we show that calcium cations strongly bind to alginate by disrupting hydrogen bonds within (1 → 4)-linked β-d-mannuronate (M) residues. On the other hand, Na+ cations enhance intramolecular hydrogen bonds that stabilize a left-hand, fourfold helical chain structure in poly-M alginate, resulting in stiffer chains. Hence, the traditionally accepted flexible flat-chain model for poly-M sequence is not valid in the presence of Na+. The two cations have a distinct effect on water coordination around alginate and therefore on its solubility. While Ca+ disrupts water coordination directly around the alginate chains, mobile Na+ cations significantly disrupt the second hydration layer.

How Accurate Is the Egg-Box Model in Describing the Binding of Calcium to Polygalacturonate? A Molecular Dynamics Simulation Study

“…These results imply that the EBM is not well-suited to describing the local coordination of calcium to polyGalA, given that (i) their coordination to carboxylate groups is preferentially bidentate and (ii) their coordination to other oxygen atoms from GalA units is very unlikely. These results confirm those found for previous unbiased and shorter MD simulations on calcium–polyuronate systems. − , …”

“…(These two coordination modes represent 50−52 and 45−47% of the ionic bridges, respectively, while the monodentate−monodentate coordination mode accounts for the remaining 3%.) These results corroborate the bidentate association of Ca 2+ to GulA units found in several MD studies [6][7][8]59 and contradict the EBM, which assumes the participation of three oxygen atoms from each GalA chain to the coordination of calcium cations. We actually showed in a previous MD study that the coordination mode (monodentate or bidentate) of a divalent cation (Ba 2+ , Ca 2+ , Mg 2+ , or Zn 2+ ) to the carboxylate group of GalA depends on its affinity for water.…”

“…These discrepancies may probably be ascribed to an overestimation of the affinity between calcium and the carboxylate group of uronates owing to the difficulty in accurately representing the binding constant between divalent cations and negatively charged groups with fixed-charged empirical force fields. ,, This difficulty may be further illustrated with the MD study by Fu et al, who determined a standard binding free energy of −5.4 kcal·mol –1 for the binding of calcium to a GulA unit that is similar to that determined by Fang et al (23 kJ mol –1 = 5.5 kcal·mol –1 ) for alginate chains with high degrees of polymerization (170 and 2000) using ITC . Moreover, Peric et al found the association of Ca 2+ to single polyuronate chains to be essentially nonspecific, in agreement with the counterion condensation theory of Manning, whereas Li et al recently showed that calcium is overwhelmingly found in the first coordination shell of carboxylate oxygen atoms of single polyGulA and polyManA chains. The comparison between these MD simulation results clearly underlines the strong dependence of the calcium–uronate association mode on the empirical force field parameters used to perform simulations.…”

“…Fu et al called "perfect egg-box structure" local coordination geometries where calcium is coordinated to the carboxylate groups of GulA in a bidentate coordination mode, 8 which would correspond to an EBS of 0.4, while Li et al referred to geometries in which calcium is coordinated to at least three oxygen atoms of a single alginate chain as "classic egg-box". 59 Local Helical Parameters of PolyGalA Chains. We determined the local helical parameters of polyGalA chains, namely, the helix raise h and the helix turn angle θ, in a similar way as in Peric et al 61 (See Figure S10 in the Supporting Information for further details.)…”

“…The Journal of Physical Chemistry B pubs.acs.org/JPCB Article condensation theory of Manning, 67 whereas Li et al 59 recently showed that calcium is overwhelmingly found in the first coordination shell of carboxylate oxygen atoms of single polyGulA and polyManA chains. The comparison between these MD simulation results clearly underlines the strong dependence of the calcium−uronate association mode on the empirical force field parameters used to perform simulations.…”