A non-classical view on calcium oxalate precipitation and the role of citrate

Abstract

Although calcium oxalates are relevant biominerals, their formation mechanisms remain largely unresolved. Here, we investigate the early stages of calcium oxalate formation in pure and citrate-bearing solutions. Citrate is used as a well-known oxalate precipitation inhibitor; moreover, it resembles the functional domains of the biomolecules that modulate biomineralization. Our data suggest that calcium oxalate forms after Ca2+ and C2O4 2− association into polynuclear stable complexes that aggregate into larger assemblies, from which amorphous calcium oxalate nucleates. Previous work has explained citrate inhibitory effects according to classical theories. Here we show that citrate interacts with all early stage CaC2O4 species (polynuclear stable complexes and amorphous precursors), inhibiting calcium oxalate nucleation by colloidal stabilization of polynuclear stable complexes and amorphous calcium oxalate. The control that citrate exerts on calcium oxalate biomineralization may thus begin earlier than previously thought. These insights provide information regarding the mechanisms governing biomineralization, including pathological processes (e.g., kidney stone formation).

From Solute, Fluidic and Particulate Precursors to Complex Organizations of Matter

“…With heterogeneous compositions, the solute clusters exhibit relatively distinct properties of stability, structure and solvation. For instance, poly‐dentate ligands such as phytic acid and citric acid associate with ions and ion‐clusters, producing polynuclear complexes ,. With increasing supersaturation levels, these hybrid complexes aggregate into larger assemblies and subsequently nucleate particles.…”

How Can Additives Control the Early Stages of Mineralisation?

“…Additive-controlled mineralization, in the broadest sense, is central to various fields [1][2][3], ranging from biomineralisation [4][5][6][7][8] to scale inhibition [9][10][11]. It also touches upon materials chemistry, where the realisation of target-oriented synthetic routes to hybrid materials with advanced properties is every researcher's dream [12].…”

Harnessing Calcium‐Oxalate‐ (CaOx‐) Nanocrystal‐Induced Prodeath Autophagy for Attenuating Human Renal Proximal Tubular Epithelial Cell Injury

“…Calcium oxalate (CaOx) is the most common type of kidney stones, up to 75–90%, and the recurrence rate is approximately 50% within 10 years . The supersaturation, nucleation, growth, aggregation to crystals followed by direct adhesion on renal tubular epithelial cells is the general process of CaOx stones formation in the kidney, further leading to pain, urinary tract infections, chronic renal disease, and even loss of kidney function . However, the definite mechanisms regarding how and when CaOx stones damage kidney remain poorly understood.…”