Molecular recognition and crystal energy landscapes: an X-ray and computational study of caffeine and other
Lucia Carlucci1, Angelo Gavezzotti
1Dipartimento di Chimica Strutturale e Stereochimica Inorganica, Università di Milano, via Venezian 21, 20133 Milano, Italy.
Abstract:
We introduce a new approach to crystal-packing analysis, based on the study of mutual recognition modes of entire molecules or of molecular moieties, rather than a search for selected atom-atom contacts, and on the study of crystal energy landscapes over many computer-generated polymorphs, rather than a quest for the one most stable crystal structure. The computational tools for this task are a polymorph generator and the PIXEL density sums method for the calculation of intermolecular energies. From this perspective, the molecular recognition, crystal packing, and solid-state phase behavior of caffeine and several methylxanthines (purine-2,6-diones) have been analyzed. Many possible crystal structures for anhydrous caffeine have been generated by computer simulation, and the most stable among them is a thermodynamic, ordered equivalent of the disordered phase, revealed by powder X-ray crystallography. Molecular recognition energies between two caffeine molecules or between caffeine and water have been calculated, and the results reveal the largely predominant mode to be the stacking of parallel caffeine molecules, an intermediately favorable caffeine-water interaction, and many other equivalent energy minima for lateral interactions of much less stabilization power. This last indetermination helps to explain why caffeine does not crystallize easily into an ordered anhydrous structure. In contrast, the mono- and dimethylxanthines (theophylline, theobromine, and the 1,7-isomer, for which we present a single-crystal X-ray study and a lattice energy landscape) do crystallize in anhydrous form thanks to the formation of lateral hydrogen bonds.
Related Concept Videos
02:00Molecular Models
02:18X-ray Crystallography
Diffraction
Diffraction is the change in the direction of travel experienced by an electromagnetic wave when it encounters a physical barrier whose dimensions are comparable to those of the wavelength of the light. X-rays are electromagnetic radiation with wavelengths about as long as the distance between neighboring...
02:58Crystal Field Theory - Octahedral Complexes
To explain the observed behavior of transition metal complexes (such as colors), a model involving electrostatic interactions between the electrons from the ligands and the electrons in the unhybridized d orbitals of the central metal atom has been developed. This electrostatic model is crystal field theory (CFT). It helps to understand, interpret, and predict the colors, magnetic behavior, and some structures of coordination compounds of transition metals.
CFT focuses on...
02:30Stability of Substituted Cyclohexanes
The two chair conformations of cyclohexanes undergo rapid interconversion at room temperature. Both forms have identical energies and stabilities, each comprising equal amounts of the equilibrium mixture. Replacing a hydrogen atom with a functional group makes the two conformations energetically non-equivalent.
For example, in...
01:10X-ray Diffraction of Biological Samples
According to Bragg's law, when X-rays strike the sample positioned on a stage, the rays are scattered by the electron clouds around the sample atoms. The X-ray diffraction or scattering is caused by constructive interference of the X-ray waves that reflect off the internal crystal...
01:29Determination of Crystal Structures