dGPredictor: Automated fragmentation method for metabolic reaction free energy prediction and de novo pathway design

Group contribution (GC) methods are conventionally used in thermodynamics analysis of metabolic pathways to estimate the standard Gibbs energy change (ΔrG′o) of enzymatic reactions from limited experimental measurements. However, these methods are limited by their dependence on manually curated groups and inability to capture stereochemical information, leading to low reaction coverage. Herein, we introduce an automated molecular fingerprint-based thermodynamic analysis tool called dGPredictor that enables the consideration of stereochemistry within metabolite structures and thus increases reaction coverage. dGPredictor has comparable prediction accuracy compared to existing GC methods and can capture Gibbs energy changes for isomerase and transferase reactions, which exhibit no overall group changes. We also demonstrate dGPredictor’s ability to predict the Gibbs energy change for novel reactions and seamless integration within de novo metabolic pathway design tools such as novoStoic for safeguarding against the inclusion of reaction steps with infeasible directionalities. To facilitate easy access to dGPredictor, we developed a graphical user interface to predict the standard Gibbs energy change for reactions at various pH and ionic strengths. The tool allows customized user input of known metabolites as KEGG IDs and novel metabolites as InChI strings (https://github.com/maranasgroup/dGPredictor).

Synthesis, Characterization and Thermodynamics of Exchange Using Zirconium Titanium Phosphate Cation Exchanger

A mixed material of the class of tetravalent bimetallic acid (TBMA) salt - zirconium titanium phosphate (ZTP) - has been synthesized by the sol-gel technique. ZTP has been characterized by elemental analysis, thermal analysis (TGA, DTA), FTIR, X-ray diffraction and SEM. Ion exchange capacity (IEC) of the material has been determined and the effect of calcination (373-773 K) on IEC studied and chemical stability of the material in various media (acids, bases and organic solvents) assessed. Further, the equilibrium exchange of H in ZTP for Mg2+, Ca2+, Sr2+ and Ba2+ ions has been studied at 303, 313, 323 and 333 K at constant ionic strength. On the basis of the exchange isotherms, various thermodynamic parameters such as equilibrium constant (K), standard gibbs energy change (∆Go), entropy change (∆So) and enthalpy change (∆Ho) have been calculated. The parameters were correlated with the ion exchange characteristics of the material.

Size dependence of the solubility of nonpolar compounds in different solvents

At 25°C, plots of the standard Gibbs energy change associated with the solvation of noble gases and aliphatic hydrocarbons vs. the size of the solutes prove to be approximately linear with a negative slope for common organic solvents but not for water. In the latter case, the plot has a characteristic V-shape. The slope is negative for noble gases, methane, and ethane, but is positive for larger alkanes. This means that the solubility of nonpolar solutes increases with solute size in every solvent except water. The solvation thermodynamics of noble gases and aliphatic hydrocarbons in five solvents (water, ethanol, benzene, c-hexane, and n-hexane) are analyzed in detail by a general theory, which is rederived to avoid risky misunderstandings. The calculations are performed in the same manner for all solvents, using simple formulas where the physical reliability is well established and the results are consistent. The work of cavity creation increases with solute size in every solvent, but to a far greater extent in water. Additionally, the work to turn on the solute–solvent attractive interactions increases in magnitude with solute size in every solvent, but to a lesser extent in water. By combining these two factors a satisfactory explanation for experimental data obtained emerges. The microscopic origins of the difference between water and common organic solvents are discussed.Key words: solvation, excluded-volume effect, solute–solvent interactions, enthalpy–entropy compensation, molecular size.

Solvation of a water molecule in cyclohexane and water

Reliable values for the thermodynamic functions associated with the solvation of a water molecule in its own liquid phase and in cyclohexane, at 25°C, are obtained using experimental data from different investigations. They are successfully rationalized by means of a general theory of solvation. The standard Gibbs energy change is given by the balance of two contrasting terms: the work to create a cavity in the solvent suitable to host the water molecule; and the work to turn on the water-solvent interactions. It proves that the work of cavity creation is largely overwhelmed by the formation of two H-bonds in liquid water, whereas it is almost exactly counterbalanced by the establishment of van der Waals interactions in liquid cyclohexane.Key words: water, cavity creation, H-bonds, van der Waals interactions.