ABSTRACT
Irbesartan (IBS) is a tetrazole derivative and antihypertensive drug that has two interconvertible struc-tures, 1H-and 2H-tautomers. The difference between them lies in the protonation of the tetrazole ring. In the solid-state, both tautomers can be isolated as crystal forms A (1H-tautomer) and B (2H-tautomer). Studies have reported that IBS is a polymorphic system and its forms A and B are related monotropically. These reports indicate form B as the most stable and less soluble form. Therefore, the goal of this contribution is to demonstrate through a complete solid-state characterization, thermodynamic study and dissolution properties that the IBS forms are desmotropes that are not related monotropically. However, the intention is also to call attention to the importance of conducting strict chemical and in solid-state quality controls on the IBS raw materials. Hence, powder X-ray diffraction (PXRD) and Raman spectroscopy (RS) at ambient and non-ambient conditions, differential scanning calorimetry (DSC), hot stage microscopy (HSM), Fourier transform infrared (FT-IR) and scanning electron microscopy (SEM) techniques were applied. Furthermore, intrinsic dissolution rate (IDR) and structural stability studies at 98％relative humidity (RH), 25 ?C and 40 ?C were conducted as well. The results show that in fact, form A is approximately four-fold more soluble than form B. In addition, both IBS forms are stable at ambient conditions. Nevertheless, structural and/or chemical instability was observed in form B at 40 ?C and 98％RH. IBS has been confirmed as a desmotropic system rather than a polymorphic one. Consequently, forms A and B are not related monotropically.
ABSTRACT
A novel Schiff base (Z)-4-(((2-hydroxy phenyl)amino)(phenyl)methylene)-3-methyl-1-phenyl-1Hpyrazol- 5(4H)-one and its analogues were synthesized by condensation of 5-methyl-2-phenyl-4-substituted pyrazolin- 3-one with 2-amino phenol from alcoholic solution.Schiff base ligands arecharacterizedby IR, UV, NMR, elemental analysis and single crystal X- ray diffraction analysis. These potential ligands are subjected to DNA binding analysis against the Calf thymus DNA, their binding constant values were calculated and compared to the standard ruthenium intercalators. The cytotoxic natureof these Schiff base ligands was also studied with the human breast cancer cell line MCF-7 and their IC50 values were determined.
ABSTRACT
The tautomerism of the natural 1-substituted pyrimidines and 9-substituted purines found in nucleic acids has been re-examined in the light of new experimental data on various nitrogen heterocycles in solution, in the gas phase and, in part, in low-temperature inert matrices. The results are compared with those obtained by quantum chemical calculations, including improved versions of the latter. Examples are presented of natural nucleosides which exhibit appreciable tautomerism in solution, e.g. formycins A and B, isoguanosine, but are not found in DNA. Illustrations are given of synthetic promutagenic nucleosides with pronounced tautomerism in solution relevant to their role in mutagenesis, such as the N4-hydroxy- and N4-methoxy cytidines. The amino-imino tautomeric equilibria of the promutagenic N6-hydroxy- and N6 -methoxy-adenosines are highly dependent on the solvent medium, the proportion of the imino species varying from 10% in CCl4 to 90% in aqueous medium. The type of base pairing of these is dependent on the conformation of the exocyclic hydroxy or methoxy groups. At the monomer level, addition of a potentially complementary base leads to a shift in the tautomeric equilibrium in favour of the species which pairs with this base. Biological and genetical implications of the foregoing are described.