Experimental Determination of Melting Properties of Biological Compounds for Better Solubility Predictions

• Applicants: Dr. Yeong Zen Chua; Privatdozent Dr.-Ing. Christoph Held
• Subject Area: Technical Thermodynamics ; Chemical and Thermal Process Engineering
• Term: from 2017 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 327337994

Knowledge about solubility of biomolecules is crucial for the designand optimization of production of amino acids, peptides, proteins, andpharmaceuticals. Product purity, supersaturation ratios ofbiomolecules in solution as well as choice of a suitable solventdepend on solubility. In many cases, data on the influence ofparameters like temperature, pH-value, kind and concentration of cosolventsand co-solutes on biomolecule solubility are insufficient.Modeling solubility behavior has thus attracted research interest inchemical engineering science. However, the results of pure solubilitypredictions using thermodynamic models are still not satisfying. Thisis mainly caused by wrong or not available data of the meltingproperties of the biomolecules. The experimental determination ofmelting properties such as melting temperature TSL, melting enthalpyhSL, or heat capacities cpSL with conventional methods often failscaused by decomposition of the biomolecules at temperatures belowTSL. Application of group-contribution methods that might be used toestimate melting properties might yield to very high uncertainties oreven to non-consistent data. In the last years, the new method FastScanning Chip Calorimetry (FSC) has been developed in order todetermine melting properties (TSL, hSL, cpSL) experimentally. This isof special importance for biomolecules, as these compoundsdecompose before melting. Applying of very high heating rates (< 10Mio. K/s) allows reducing the time for decomposition at hightemperatures dramatically compared to conventional methods (< 1K/s). Decomposition thus takes place at much higher temperatures. Incontrast, melting depends only slightly on heat rate. This allows phasechange and experimental determination of melting properties. In thisproposed project, FSC will be further developed in order to determinequantitatively data for TSL, hSL and cpSL for biomolecules (aminoacids, peptides, proteins). The compound class of dipeptides shall bewithin closer focus of this project as solubility and melting propertiesof dipeptides are not well investigated. The melting properties whichwill be determined by FSC will be used as input into thermodynamicmodels for the prediction of solid-liquid equilibria. Thiswill allowpredicting the solubility of biomolecules in solvents and solventmixtures depending on temperature and pH-value. In order to reach the goal, the complementary research fields equilibriumthermodynamics and experimental calorimetry have to be combined.These fields belong to the research competences of Christoph Heldand Andreas Wurm, who are applying for this project.

• DFG Programme: Research Grants