Knight, Brenna M.Mondal, RonnieHan, NizhouPietra, Nicholas F.Hall, Brady A.Edgar, Kevin J.Welborn, Valerie VaissierMadsen, Louis A.De Yoreo, James J.Dove, Patricia M.2025-11-072025-11-072024-07-111528-7483https://hdl.handle.net/10919/138894Anionic macromolecules are found at sites of CaCO3 biomineralization in diverse organisms, but their roles in crystallization are not well-understood. We prepared a series of sulfated chitosan derivatives with varied positions and degrees of sulfation, DS(SO3-), and measured calcite nucleation rate onto these materials. Fitting the classical nucleation theory model to the kinetic data reveals the interfacial free energy of the calcite-polysaccharide-solution system, gamma(net), is lowest for nonsulfated controls and increases with DS(SO3-). The kinetic prefactor also increases with DS(SO3-). Simulations of Ca2+-H2O-chitosan systems show greater water structuring around sulfate groups compared to uncharged substituents, independent of sulfate location. Ca2+-SO3- interactions are solvent-separated by distances that are inversely correlated with DS(SO3-) of the polysaccharide. The simulations also predict SO3- and NH3+ groups affect the solvation waters and HCO3- ions associated with Ca2+. Integrating the experimental and computational evidence suggests sulfate groups influence nucleation by increasing the difficulty of displacing near-surface water, thereby increasing gamma(net). By correlating gamma(net) and net charge per monosaccharide for diverse polysaccharides, we suggest the solvent-separated interactions of functional groups with Ca2+ influence thermodynamic and kinetic components to crystallization by similar solvent-dominated processes. The findings reiterate the importance of establishing water structure and properties at macromolecule-solution interfaces.application/pdfenCreative Commons Attribution 4.0 InternationalArticle - Refereedhttps://doi.org/10.1021/acs.cgd.4c006022415391314461528-7505