https://hdl.handle.net/10259/4323 2026-04-20T06:11:06Z https://hdl.handle.net/10259/11439 Molecular mechanisms of β-cyclodextrin solubilization in natural deep eutectic solvents: A quantum chemical investigation Huerta Sainz, Sergio de la; Escobedo Monge, María Antonieta; Escobedo-Monge, Marlene Fabiola; Bol Arreba, Alfredo; Marcos Villa, Pedro A.; Atilhan, Mert; Aparicio Martínez, Santiago Cyclodextrins, particularly β-cyclodextrin (β-CD), exhibit remarkable host-guest complexation capabilities due to their unique toroidal structures. Natural deep eutectic solvents (NADES), biocompatible mixtures of readily available components, represent sustainable alternatives to conventional solvents with tunable physicochemical properties. This work investigates the molecular interplay between β-CD and NADES, focusing on their potential to create sustainable, multifunctional materials. Two configurations were explored: (i) β-CD dissolved in NADES and (ii) β-CD acting as a NADES component. Using density functional theory simulations, the study examined intermolecular forces, confinement effects, and molecular topology to characterize host–guest interactions between atomistic models of selected NADES (menthol + thymol and menthol + decanoic acid) and β-CD complexes. Energetic and kinetic analyses provided insights into the driving forces and timescales of complexation processes. The findings contribute to a mechanistic understanding of NADES–CD systems, enabling rational selection of solvent compositions and cyclodextrin forms for optimized guest encapsulation and targeted functionalities. 2026-02-01T00:00:00Z https://hdl.handle.net/10259/11438 Nature's tool kit: Designing biocompatible and affordable NADES for sustainable extraction of plant bioactives Huerta Sainz, Sergio de la; Escobedo Monge, María Antonieta; Marcos Villa, Pedro A.; Esteban-Ollo, José Antonio; Montejo-Gil, Laura; Conde-Rioll, María; Atilhan, Mert; Bol Arreba, Alfredo; Aparicio Martínez, Santiago Conventional extraction of valuable plant compounds often relies on hazardous volatile organic solvents (VOCs), posing environmental and health risks. This study explores a sustainable alternative using Natural Deep Eutectic Solvents (NADES) designed in-silico through the Conductor-like Screening Model for Realistic Solvents methodology (COSMO-RS) for efficient extraction of target plant metabolites. A library of NADES with varying compositions was designed using COSMO-RS to predict their physicochemical properties and affinity for target natural compounds, selecting the most promising candidates in terms of versatility, cost-effectiveness and biocompatibility. To complete the study, a predictive Artificial Intelligence based method (Decision Trees) was developed for reverse design of NADES for target bioactive compounds from energetic and structural molecular descriptors. From a compendium of 58 plant metabolites of interest and 66 natural compounds as NADES components, nearly 3000 solubility in silico tests were conducted and a total of 12 NADES were selected. Three solubility models were created, and a clear dependance of the target compound properties was observed. 2025-03-01T00:00:00Z https://hdl.handle.net/10259/11437 Beyond the blend: Unveiling the thermophysical fingerprints of hydrated choline chloride deep eutectic systems with bio-derived and synthetic hydrogen bond donors Alcalde García, Rafael T.; Huerta Sainz, Sergio de la; Diez Cabanes, Valentin; Escobedo Monge, María Antonieta; Trenzado, José Luis; Atilhan, Mert; Bol Arreba, Alfredo; Aparicio Martínez, Santiago This study presents a comprehensive thermophysical characterization of hydrated deep eutectic solvents (DESs) composed of choline chloride (ChCl) and four hydrogen bond donors (HBDs): citric acid, malic acid, fructose, and ethylene glycol in equimolar ratios. By introducing 2, 10, and 22 wt% water—spanning key hydration regimes where DESs structure is progressively altered—we systematically quantify the effects of hydration on density, viscosity, electrical conductivity, thermal conductivity, and refractive index over a wide temperature range. Results demonstrate that water addition leads to a dramatic reduction in viscosity, particularly for bio-derived HBDs, enhancing processability and enabling practical applications. The ChCl:citric acid DESs maintains high structural cohesion upon hydration, reflected in persistent cooperative dynamics and high activation energy, whereas the synthetic ethylene glycol system exhibits predictable, tunable behavior, ideal for engineered fluid systems. Electrical conductivity increases non-linearly with water content, accompanied by a transition from fragile to strong liquid behavior. Derived parameters—molecular volume, thermal expansion coefficient, and excess molar volumes—reveal non-ideal mixing behavior and structural reorganization. Our findings define structure–property correlations critical for optimizing DESs formulations, offering a foundation for application-specific solvent engineering in energy, electrochemistry, and separation technologies. 2025-11-01T00:00:00Z https://hdl.handle.net/10259/11436 In silico characterization of Ciwujianoside E: Structural features, solvation dynamics, and eco-toxicological assessment Navarro Cuñado, A. Marta; Tapia Estévez, M.ª José; Huerta Sainz, Sergio de la; Gutiérrez Vega, Alberto; Aparicio Martínez, Santiago This work presents an in-depth characterization of Ciwujianoside E through Density Functional Theory (DFT) and Quantum Theory of Atoms in Molecules (QTAIM) analyses. We investigated multiple conformers, revealing the critical electronic and geometric properties that influence molecular behavior. This study includes electron density distributions and topological characteristics defining the structural integrity, along with a detailed hydrogen bonding network analysis. High-level quantum mechanical calculations provide precise geometric optimization for various conformer configurations. Complementary, molecular docking studies have assessed interactions with human proteins and plasma membranes, elucidating binding mechanisms with potential pharmacological and/or toxicological significance. Likewise, the possibility of using Deep Eutectics Solvents (DES) for the extraction of Ciwujianoside E as an environmentally friendly extraction procedure was considered when designing suitable molecular combinations to improve affinity and target molecule solubility. Moreover, the solvation mechanism(s) of Ciwujianoside E in water and Deep Eutectic Solvents were analyzed via Molecular Dynamics simulations. This integrated computational approach provides a comprehensive insight into the molecular characteristics of Ciwujianoside E. 2025-01-01T00:00:00Z