Molecule, design optimization formulations

The objective of this chapter is to show how the concepts of chemical kinetics can be applied to the passage of molecules across the skin. The barrier function of the skin is still not totally understood but application of kinetic principles has allowed us to gain a better understanding of the barrier and how penetration enhancers may modulate it. The application of kinetics has allowed a mechanistic interpretation and therefore the development of predictive models. These can assist in the identification and design of novel transdermal drugs, and in the optimal design of topical formulations. 

This work has focused on the use of optimization techniques within a molecular design application to derive novel catalyst structures. The use of connectivity indices to relate internal molecular structure to physical properties of interest provides an efficient way to both estimate property values and recover a complete description of the new molecule after an optimization problem is solved. The optimization problem has been formulated as an MINLP, and the fact that the problem has been formulated in a manner which is not computationally expensive to solve (using Tabu search) gives rise to the possibility that the synthesis route for such a molecule could be derived and evaluated along with the physical properties of that molecule. Further work will include such synthesis analysis, as well as the inclusion of a much larger set of physical properties and basic groups from which to build molecules, and will work toward the design of mixtures and the prediction of mixture properties via connectivity indices. 

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