Stereochemistry and Anti-Inflammatory Inhibition: Asymmetry, And Complexes Of 4-Halogenated Mofebutazones Derivatives

Abstract

The role of halogens in racemic 4-hal-4-butyl (n-oc­tyl)-1phenyl derivatives (hal: F, Cl, Br), of the cyclic pyr­azoline(1,3)-diones in the solid state and in solution was determined [1]. Noncovalent interactions are observed for the F, Cl and Br derivatives between the halogen atom and the hydrogen atom of the nitrogen of the pyr­azolidine ring, water hydrogens that interact either with the halogen atoms or with the carbonyl oxygen atoms very different from the none-halogenated pyrazoline-di­ones [2-5]. The 3d and 2d structures are stabilized by - and - interactions, intermolecular distances, and apolar forces between adjacently stacked phenyl rings. However, the R-or S-enantiomers or their water-stable complexes with Znmeglumine did not racemizes in aqueous dis­persions [1,3]. Small-angle-, wide-angle x-ray scattering experiments, and molecular simulation reveal similar solution structure factors, S(Q), in the solid state and in solution [6,7]. The planes and their periodicities of the crystalline phases are preserved in the aqueous solution phase. There is also hydrogen bonding formed in the ra­cemic and the R-enantiomeric n-octyl-1phenyl-1-Cl-pyr­azoline-(1,3)-dione between the hydrogens of the water molecules and the halogens of the pyrazolidine ring: Cl forms a hydrogen bond to the water hydroxy group of a neighbouring molecule, which is hydrogen bonded to the chlorine of another molecule forming a 1-dimen­sional hydrogen-chloride bond network differently from hydrated cationic lipids or their polymorphs [8,9]. The n-octyl pyrazolidine approximant forms micelles in aque­ous dispersions that selfassemble into quasicrystalline structures. The small-angle X-ray scattering experiments and the selected area electron diffraction pattern of thin films suggest that the micelle FCC phase transforms into a colloidal quasicrystalline phase with 12-fold symmetry that proceed through rearrangements of the micelles in the (111) layers of the FCC phase. The differences of the halogenated cyclic and non-cyclic pyrazoline diones are related to biochemical changes in anti-inflammatory ac­tivities. The n-octyl compound reveal antimicrobial and antiviral (influenza) activities but no anti-inflammatory or analgesic activities.