Density Functional Molecular Computations on Protonated Serotonin in the Gas Phase and Various Solvent Media

5-Hydroxytryptamine (serotonin) was geometry optimized at the B3YP/6-31G(d) level of theory to determine the energetically most favourable conformations of the aromatic hydroxyl group and the protonated ethylamine side chain. The hydroxyl group was found to be most stable at anti for all conformations, and the two lowest energy gas phase conformers found were: chi(2) = g(+), chi(3) = g(-) and chi(2) = g(-), chi(3) = g(+). The protonated amino group was found equally stable at g+, g- and anti. The transition structures linking each gas phase minimum were also computed. Minima found were subjected to solvation calculations in chloroform, DMSO, ethanol and water, which shifted their relative stabilities. (C) 2002 Elsevier Science B.V. All rights reserved

Density Functional Molecular Study on the Full Conformational Space of the S-4-(2-Hydroxypropoxy)carbazol Fragment of Carvedilol (1-(9H−Carbazol-4-yloxy)-3- [2-(2-methoxyphenoxy)ethylamino]-2-propanol) in Vacuum and in Different Solvent Media

Density functional theory (DFT) conformational analysis was carried out on the potential energy hypersurface (PEHS) of the carbazole-containing molecular fragment, S-4-(2-hydroxypropoxy)-carbazol, of the chiral cardiovascular drug molecule carvedilol, (1-(9H-carbazol-4-yloxy)-3-[2-(2-methoxy-phenoxy)ethylamino]-2-propanol) . The PEHS was computed in vacuum, chloroform, ethanol, DMSO, and water at the B3LYP/6-31G(d) level of theory. The carbazole ring system was confirmed to be planar, and the resultant PEHS in vacuum contained 19 converged minima, of which the global minima possessed a conformation with chi(1), chi(2), and chi(3) in the anti position and chi(10) in the g position. Conformer stability for the S-4-(2-hydroxypropoxy)carbazol PEHS was influenced by intramolecular hydrogen bonding. Tomasi PCM reaction-field calculations revealed that the lowest SCF energies, relative conformer energies, and solvation free energies (DeltaG (solvation)) for the S-4-(2-hydroxypropoxy)carbazol PEHS were in protic solvents, ethanol and water, because of the larger hydrogen bond donor values of these solvents, which aid in stabilization of the dipole moment created by the carbazole ring system and the oxygen and nitrogen atoms. However, solvent effects contributed most significantly to the stabilization of S-4-(2-hydroxypropoxy)carbazol conformers that contained no internal hydrogen bonding, whereas solvent effects were not as important for conformers that contained intramolecular hydrogen bonding