COSMOthermSelected industrial applications

J. Reinisch, Copyright COSMOlogic GmbH & Co. KG

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Phase Separations (DuPont)Boiling Points of HFC compounds

S.Lustig*, A. Klamt, presented at InMoTher 2012, Lyon, France, (*DuPont)

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Phase Separations (DuPont)Henry’s Law Constants of HFC’s in Ionic Liquids

S.Lustig*, A. Klamt, presented at InMoTher 2012, Lyon, France, (*DuPont)

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• Excipients are pharmaceutically inactive substances bulking up API formulations.

• They can solubilize drugs with low aqueous solubility and solubility-limited exposure in vivo.

• COSMO-RS solubility screening will identify excipients with high API solubility:

„This approach enables the formulator to quickly narrow down the number of excipients used for solubility screening and formulation development in the lab without requiring any physico-chemical information on the compound.”*

Solvent Screening (Pfizer)Case study: Excipient ranking in formulation

*Pozarska, A.; da Costa Mathews, C.; Wong, M.; Pencheva, K., Eur. J. Pharm. Sci., 2013, 49, 505. (Pfizer Inc)

Danazol

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Cocrystal Screening (NALAS Engineering)Case study: Energetic Materials

• Cocrystals like HMX:CL-20 are desirable because they have a higher energy density than the pure compounds.

• Cocrystal formation tendency is confirmed by ranking of COSMO-RS DHMix=DHEx

am Ende, D.; Anderson, S; Salan J. „Cocrystals via Resonant Acoustic Mixing“, presented at 11th ICEPC May 2014. (NALAS Engineering Services, Inc.)

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Solvent effects on chemical reactions

Chemical Reactions

DGREACTION

DGACTIVATION

Different

Solvents

The influence of difference solvents can be described by COSMO-RS via the free energy differences of reactants, transition state and products:

DGREACTION Equilibrium Constant

DGACTIVATION Kinetic Constant

Reactants Transition State Products

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Concept

• Compute DGactivation and/or DGreaction in vacuum by high-level quantum chemistry

• Solvent effects can be considered by adding COSMOtherm computed free energy of solvation DGsolv of educts, products, or transition states

Successful applications have been reported by a number of industrial users:

Dr. Franke, Evonik Industries AG; Dr. Lohrenz, Bayer AG, Dr. Deglmann, BASF

Free energy of solvation

Chemical Reactions

Reactant A (g) Reactant B (g) Product C (g)Transition State (g)

Reactant A (l) Reactant B (l) Product C (l)Transition State (l)

In gas phase

In solution

DGAsolv DGB

solv DGTSsolv

DGCsolv

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Rate constants & free energy of reactions

Chemical Reactions (BASF)

* Deglmann, P.; Schenk, S. Journal of Computational Chemistry, 2012, 33, 1304. (BASF)

** Deglmann, P. et al. Macromol. React. Eng. 2009 , 3, 496. (BASF)

Absolute rate constants for bulk polymerizations**

Absolute reaction energies*