SUMMARY
The current proposal is seeking funding to achieve the fundamental goal of systematically identifying
processes that show promise during HHP activation. A broad range of reactions will be investigated by
theoretical calculations to identify processes that are stimulated by HHP. Then the selected reactions will
be studied experimentally confirm the results, and determined the extent of the pressure effect. Our own
preliminary data indicate that even a serendipitous search of reactions can yield positive results, however
the lack of systematic framework greatly inhibits progress. What makes the identification of such reaction
networks especially worthwhile is the fact that HHP equipments capable of industrial scale syntheses are
already available and commonly used in the food industry. Thus, any reaction identified in our project
could be scaled-up to industrial scale in a short time. We intend to achieve these goals in two major
steps: (1) Scanning a broad range of reactions by theoretical calculations based on the determination of
the V‡ and V values. The first aim will focus on building a reaction network by selecting a broad range
of transformations based on a literature search and carrying out the theoretical calculations to determine
the favorability rating of those reactions, and identify reactions that are being enhanced under high
pressure conditions. The second aim focuses on the experimental testing of the selected reactions as
classified by the in-silico methods to confirm that HHP in fact improves these reactions. The combination
of the data obtained in Aims 1-2, will aid us to make a more reasonable predictions regarding future
applications of HHP. Finally in aim 3 we extend the application of the HHP-based protocol to currently
known active pharmaceutical ingredients, such as pain killers (paracetamol, or Aspirin),
benzodiazepines, pyrazoles, and hydrazones to illustrate the potential usefulness of the high pressure
synthesis to the pharmaceutical industry.