Crystal structure analysis and sublimation thermodynamics of bicyclo derivatives of a neuroprotector family.
The crystal structures of three new structurally related drug-like bicyclo derivatives are correlated with measured thermodynamic quantities for their sublimation and melting processes. The sublimation thermodynamics are determined using the temperature dependencies of the vapour pressure, and the melting processes are examined using differential scanning calorimetry. The three compounds contain a common N-(3-thia-1-azabicyclo[3.3.1]non-2-ylidene)aniline core, with either a CH3, F or CF3 substituent at the 4-position of the aniline ring. Lattice energy calculations are made using both the PIXEL and Coulomb-London-Pauli (CLP) models, and the conformational flexibility of the molecules is examined using gas-phase density functional theory (DFT) calculations. The experimentally measured crystal lattice energies (ΔH(0)sub) decrease in the order: CH3 > F > CF3. The calculated lattice energies using the PIXEL approach are in good agreement with the experimental values, and the partitioned intermolecular interaction energies suggest that dispersion contributions dominate the crystal structures of all three compounds. The sublimation energies and melting points are inversely correlated for the three molecules, with the melting points increasing in the order CF3 < F < CH3.
Krestov's Institute of Solution Chemistry, Russian Academy of Sciences, Ivanovo 153045, Russian Federation.
Artem O
AO
Surov
Institute of Physiologically Active Compounds, Russian Academy of Sciences, Chernogolovka 142432, Russian Federation.
Alexey N
AN
Proshin
Krestov's Institute of Solution Chemistry, Russian Academy of Sciences, Ivanovo 153045, Russian Federation.
German L
GL
Perlovich
D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D008968:Molecular Conformation; D018696:Neuroprotective Agents / Q000737:chemistry*; D000074706:Sublimation, Chemical; D013816:Thermodynamics
D019086:Bridged Bicyclo Compounds, Heterocyclic; D018696:Neuroprotective Agents
bicyclo derivatives; crystal lattice energy; sublimation thermodynamics