Theoretical study of morphine and heroin: Conformational study in gas phase and aqueous solution and electron distribution analysis

Abstract

ABSTRACT:The conformational preferences of morphine and heroin were studied in gas phase and with inclusion of solvent effects. At 298.15 K, three conformers are significant for isolated morphine, all of them displaying antiperiplanar arrangement for the C2AC3AOAH unit, and there is only one significantly populated conformer for heroin. Quantum theory of atoms in molecules analysis of the electron density in their most populated conformers in gas phase indicates that the positive charge is shared among the amino hydrogen, those hydrogens of the methylamino group, and all of the hydrogens attached to the bridgehead carbons.

Conformational complexity of morphine and morphinum in the gas phase and in water. A DFT and MP2 study

“…The axial conformations of morphine, not considered in previous works, were included. [20][21][22] This study reveals that axial conformers are not much higher in energies than their equatorial counterparts and should denitely be taken into consideration. No similar calculations have previously been reported for morphinum, the predominating species in water solutions at physiological pH and the rst results are therefore reported herein.…”

“…Consequently, a computational study is an attractive alternative method. Computations with quantum methods restricted to equatorial conformations of morphine have recently been reported for the gas phase, [20][21][22] as well as for aqueous solution. 20 In this work, state-of-the-art quantum calculations are carried out to investigate the full conformational landscape of morphine and morphinum in the gas phase and in water solution.…”

“…Computations with quantum methods restricted to equatorial conformations of morphine have recently been reported for the gas phase, [20][21][22] as well as for aqueous solution. 20 In this work, state-of-the-art quantum calculations are carried out to investigate the full conformational landscape of morphine and morphinum in the gas phase and in water solution. The study includes calculations for equatorial morphine to a higher methodological level than previously [20][21][22] using a choice of several DFT functionals and a wave-function method, MP2.…”

“…20 In this work, state-of-the-art quantum calculations are carried out to investigate the full conformational landscape of morphine and morphinum in the gas phase and in water solution. The study includes calculations for equatorial morphine to a higher methodological level than previously [20][21][22] using a choice of several DFT functionals and a wave-function method, MP2. The axial conformations of morphine, not considered in previous works, were included.…”

Theoretical Calculations on the Conformational/Tautomeric Equilibria for Small Molecules in Solution

“…According to this theory, qualification of a hydrogen bond is related to the existence of a bond critical point (BCP) of (3,-1) type. Although a hydrogen bond may be expected on the basis of the H…X distance (X a hydrogen bond acceptor atom), the (3,-1) BCP topology was not found for 1,2-dihydroxy ethane [5], catechol [6], and morphine [7] with geometries optimized in the gas phase. Mandado et al [6] pointed out, however, that after a slight distortion of the optimized catechol geometry, the (3,-1) BCP appears.…”