The sol-gel method is versatile and one of the well-established synthetic approaches for preparing bioactive glass with improved microstructure. In a successful approach, alkoxide precursors undergo rapid hydrolysis, followed by immediate condensation leading to the formation of three-dimensional gels. On the other hand, a slow kinetics rate for hydrolysis of one or more alkoxide precursors generates a mismatch in the progression of the consecutive reactions of the sol-gel process, which makes it difficult to form homogeneous multicomponent glass products. The amorphous phase separation (APS) into the gel is thermodynamically unstable and tends to transform into a crystalline form during the calcination step of xerogel. In the present study, we report a combined experimental and theoretical method to investigate the stability towards hydrolysis of triethyl phosphate (TEP) and its effects on the mechanism leading to phase separation in 58S bioactive glass obtained via sol-gel route. A multitechnical approach for the experimental characterization combined with calculations of functional density theory (DFT) suggest that TEP should not undergo hydrolysis by water under acidic conditions during the formation of the sol or even in the gel phase. The activation energy barrier (ΔG^‡) showed a height of about 20 kcal·mol⁻¹ for the three stages of hydrolysis and the reaction rates calculated for each stage of TEP hydrolysis were k_FHR = 7.0 × 10⁻³s⁻¹, k_SHR = 6.8 × 10⁻³s⁻¹ and k_THR = 3.5 × 10⁻³s⁻¹. These results show that TEP remains in the non-hydrolyzed form segregated within the xerogel matrix until its thermal decomposition in the calcination step, when P species preferentially associate with calcium ions (labile species) and other phosphate groups present nearby, forming crystalline domains of calcium pyrophosphates permeated by the silica-rich glass matrix. Together, our data expand the knowledge about the synthesis by the sol-gel method of bioactive glass and establishes a mechanism that explains the role played by the precursor source of phosphorus (TEP) in the phase separation, an event commonly observed for these biomaterials.

溶胶-凝胶法是通用的，并且是用于制备具有改善的微结构的生物活性玻璃的公认的合成方法之一。在成功的方法中，醇盐前体会快速水解，然后立即缩合，从而形成三维凝胶。另一方面，一种或多种醇盐前体水解的慢动力学速率在溶胶-凝胶过程的连续反应的进程中产生失配，这使得难以形成均质的多组分玻璃产品。进入凝胶的无定形相分离（APS）在热力学上是不稳定的，并且在干凝胶的煅烧步骤中倾向于转变为结晶形式。在目前的研究中，我们报告了一种组合的实验和理论方法，以研究对磷酸三乙酯（TEP）水解的稳定性及其对导致通过溶胶-凝胶途径获得的58S生物活性玻璃中相分离机理的影响。一种用于实验表征的多技术方法，结合功能密度理论（DFT）的计算表明，TEP不应在酸性条件下在溶胶形成过程中甚至在凝胶相中被水水解。活化能垒（一种用于实验表征的多技术方法，结合功能密度理论（DFT）的计算表明，TEP不应在酸性条件下在溶胶形成过程中甚至在凝胶相中被水水解。活化能垒（一种用于实验表征的多技术方法，结合功能密度理论（DFT）的计算表明，TEP不应在酸性条件下在溶胶形成过程中甚至在凝胶相中被水水解。活化能垒（ΔG ^‡）在水解的三个阶段显示出约20 kcal·mol ^-1的高度，并且对于TEP水解的每个阶段计算的反应速率为k _FHR  = 7.0 x 10 ^-3 s ^-1，k _SHR  = 6.8 x 10 ^-3 s ^-1和k _THR  = 3.5 x 10 ^-3 s ^-1。这些结果表明，当P物种优先与钙离子（不稳定的物种）和附近存在的其他磷酸基团缔合，形成钙的结晶域时，TEP仍以非水解形式保留在干凝胶基质中，直至在分解步骤中发生热分解。焦磷酸盐被富含二氧化硅的玻璃基质渗透。总之，我们的数据扩展了通过生物活性玻璃的溶胶-凝胶法进行合成的知识，并建立了一种机制来解释磷的前体来源（TEP）在相分离中的作用，这是这些生物材料中普遍观察到的事件。