Ab-Initio and Vibrational Studies on Free Base, Cationic and Derived from Antihistaminic Cyclizine Agent

MARIA J MARQUEZ; MAXIMILIANO ALBERTO IRAMAIN; SILVIA ANTONIA BRANDÁN

Indian Journal of Research

Paripex

Año: 2019 vol. 11 p. 54 - 87

2250-1991

Experimental available infrared, Attenuated Total Reflectance(ATR) and Raman spectra of cyclizine hydrochloride havebeen employed to perform the complete assignments ofexpected 120, 123 and 126 vibration modes for free base,cationic and hydrochloride species of antihistaminic cyclizine(CYC) agent combining the Scaled Quantum MechanicalForce Field (SQMFF) methodology with Ab-initiocalculations. The harmonic force fields and the forceconstants are reported for first time for those three species ofCYC by using the B3LYP/6-31G* method. The predictedinfrared, Raman and ultraviolet-visible spectra showreasonable correlations with the corresponding experimentalones. The most low solvation energy value was observed forthe free base of CYC, as compared with the corresponding toscopolamine, heroin, morphine, cocaine and tropanealkaloids. The geometrical parameters predicted for the threecyclizine species show that both phenyl rings are symmetric,as evidenced from the experimental structure. The N-CH3distances in the three species of CYC have showed that thefree base in solution presents practically the same value thanheroin and morphine in the same medium. This similarity inthe values could be attributed to that in CYC the N-CH3group is linked only to a ring(piperazine), as in heroin andmorphine and not to bicyclic rings as in cocaine, scopolamineand tropane alkaloids. The mapped Molecular ElectrostaticPotentials (MEP) surfaces reveal different nucleophilic and/orelectrophilic regions in the three species of CYC whereprobable reactions can take place. Natural bond orbital (NBO)studies show clearly that the high stabilities of free base andhydrochloride species are strongly related to the *transitions due to the two phenyl rings in their structureswhile atoms in molecules (AIM) analyses clearly supports thehigh stability of hydrochloride species in solution due to thetwo interactions, H24---H30 and ionic H43---Cl44interaction, where the strong ionic interaction is visiblyevidenced by their highest values of their topologicalproperties.