Structure of phenylbutazone and mofebutazone in the crystalline state and in solution.
The crystal structure of the keto form of phenylbutazone has been determined and compared with the molecular conformation of mofebutazone. The pronounced differences between these two structures are the conformation of the n-butyl side chain (which is extended and in trans conformation for mofebutazone, however, bent at the C gamma-position with hydrogen bonding of the gamma-hydrogen to the carbonyl C(3)--O(1) for phenylbutazone), and the in-plane conformation of the phenyl group with respect to the heterocyclic ring system in mofebutazone compared with two benzene rings at N(1) and N(2) which are almost perpendicular to the pyrazolidin-(3,5)-dione ring. Preliminary X-ray data reveal that the structures of the alkali enolates of both compounds are difficult to solve because the crystal quality is insufficient and highly disordered. However, the large unit cells are consistent with chelated structures of the alkali enolates with solvent. Sodium and potassium enolates of phenylbutazone in nonpolar solvents (e.g., benzene and cyclohexane) exist as inverse micelles comprised of 30-40 monomer units. In contrast, the salt appears to be essentially monomeric in 1,2-dimethoxyethane, and, in water for phenylbutazone, the critical micelle concentration (CMC) is greater than 0.30 M. Mofebutazone salts, however, reveal a CMC of 1.5 X 10(-3) M in water, where the basic unit of micellar aggregation seems to be the dimer. The micellar properties of phenylbutazone and mofebutazone enolates are strongly dependent on the nature of solvents, solvation of the enolate, and size of the cation. However, sodium and potassium enolates of mofebutazone in nonpolar solvents exist as small inverse micelles comprised of 8-10 monomer units only. However, in aqueous solution, weight average molecular weights of 13,100 +/- 500 were determined, with a radius of gyration of 12.85 +/- 0.55 A.
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Department of Physical Technique 7, Fachhochschule Hagen, Iserlohn, FRG.
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000032:analysis*; D001554:Benzene; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003460:Crystallization; D005615:Freezing; D008823:Micelles; D010653:Phenylbutazone / Q000031:analogs & derivatives* / Q000032:analysis*; D012542:Scattering, Radiation; D012996:Solutions; D014961:X-Ray Diffraction; D014965:X-Rays
D000894:Anti-Inflammatory Agents, Non-Steroidal; D008823:Micelles; D012996:Solutions; D010653:Phenylbutazone; D001554:Benzene; C002374:mofebutazone