A Model System of Biocompatible Organic-Inorganic Materials Containing Salicylate Peptides and Calcite: Insights into...

Biomaterials and their formation processes in living organisms (biomineralization) provide valuable bioinspired templates for the development of advanced biocompatible materials via environmentally benign synthetic routes. Calcium carbonate (CaCO₃), the principal inorganic constituent of invertebrate hard tissues, represents a particularly relevant model system for the design of novel biocomposites with potential technological and biomedical applications, including drug delivery. In natural biominerals, calcitic skeletal elements incorporate small amounts of acidic macromolecules, which are known to exert a pronounced influence on CaCO₃ polymorphism, morphology, and crystal structure when mineralization is mimicked in vitro, indicating strong and specific interactions at mineral-solution interfaces. In this study, we investigate the role of several classes of low-molecular-weight organic compounds of increasing chemical and structural complexity in the kinetics of calcium carbonate precipitation, with the aim of elucidating the extent and mechanisms of their interfacial interactions. Crystal growth kinetics of well-defined calcite seed crystals were examined in the presence of (i) selected amino acids differing in charge and polarity (aspartic acid, asparagine, lysine, phenylalanine, serine, and alanine), (ii) dipeptides (alanyl-aspartic acid, seryl-aspartic acid, seryl-serine, aspartyl-aspartic acid, and glutamyl-glutamic acid), and (iii) tripeptide aspartic acid derivatives of salicylic acid employed here as a model drug molecule. Analysis of the kinetic data using appropriate crystal growth models enabled the determination and comparison of Langmuir adsorption constants, which were used as quantitative indicators of organic-inorganic interfacial interactions. The results demonstrate that, in addition to molecular charge, hydrophobicity, conformational adaptability, and molecular flexibility play key roles in modulating calcite growth. These findings highlight critical design parameters for the development of efficient and biocompatible drug-derived additives and organic/inorganic composites. Moreover, the applied kinetic approach provides a robust framework for the rational design of biomimetic composite materials.