Influence of F...F, C-H...F and C-F...p interactions in crystal engineering: Insights for generation of new polymorphs and drug design

Ansuman Ray Chaudhuri and T. N. Guru Row

Solid State and Structural Chemistry Unit, Indian Institute of Science, Bangalore, 560012, India (ssctng@sscu.iisc.ernet.in)

Crystal engineering essentially deals with the control of packing modes in crystalline solids using suitable functional groups via well-defined directional interactions like hydrogen bonds [1]. However, along with strong intermolecular interactions such as hydrogen bonding, interactions involving halogens also significantly influence the packing of molecules in the crystalline lattice [2]. Fluorine, which commonly occurs in active drugs, is of immense interest especially how the influence of "organic fluorine" in the lattice can generate a new tool in crystal engineering [3]. A large number of crystal structures with interactions involving fluorine have to be studied to provide a rationale for the propensity of F...F to C-H...F to C-F...p be forecast. We have studied several drug and drug intermediates belonging to the isoquinoline, carboxamide, indole, and methanol series using single crystal X-ray diffraction to derive geometrical parameters for the interactions involving fluorine [4]. Interestingly, the preservation of F...F interaction in a 1:1 co-crystal of two isostructural isoquinoline based compounds having F...F interactions at different sites is unique to this class of compounds [5]. The results point to the possible exploitation of these interactions for polymorph generation in drugs and pharmaceuticals.

References

1 Desiraju, G. R., Steiner, T., The Weak Hydrogen Bond in Structural Chemistry and Biology, Oxford University Press: Oxford, 1999.

2 Ramasubbu, N., Parthasarathy, R., Murray-Rust, P., (1986) J. Am. Chem. Soc., 108, 4308.

3 (a) Prasanna, M. D., Guru Row, T. N., (2000) Cryst. Eng. Comm. 25.

(b) Prasanna, M. D., Guru Row, T. N., (2001) J. Mol. Struct., 562, 55.

4 (a) Choudhury, A. R., Urs, U. K., Guru Row, T. N., Nagarajan, K., (2002) J. Mol. Struct., 605, 71.

(b) Choudhury, A. R., Urs, U. K., Smith, P. S., Goddard, R., Howard, J. A. K., GuruRow, T. N., (2002) J. Mol. Struct., 641, 225.

5 Choudhury, A. R., Guru Row, T. N., Crystal Growth and Design (Communicated).