Intermolecular Interaction

The molecular structures, conformational stability and molecular energy profile of three derivatives of RC6H4CHNCH2CH2NCHC6H4R including N,N′-dibenzylideneethylenediamine (1, R = H), N,N′-bis(4-trifluoromethoxybenzylidene)ethylenediamine (2, R = OCF3), and N,N′-bis(4-dimethylaminobenzylidene)ethylenediamine (3, R = N(CH3)2) were obtained at B3LYP/6-31++G** and HF/6-31++G** levels of theory and compared with X-ray single crystal structures. The conformation of 1 and 2 is anti, while that of 3 is gauche in solid state (X-ray geometry). Based on calculations, there are seven energy minima in potential energy curves. A gauche conformer of 1, 2 and 3 has the lowest energy minimum (in the calculations modeling gas phase conditions) among all the other conformers. This is in contrast to X-ray findings (solid phase) for 1 and 2 but complements the X-ray finding for 3. These results were analyzed by natural bond orbital (NBO) and molecular orbital (MO) to determine the role of intra- and/or intermolecular interactions in the crystal structures.

In this review, we first summarize the structure and properties of biological membranes and the routes of passive drug transfer through physiological barriers. Lipophilicity is then introduced in terms of the intermolecular interactions it encodes. Finally, lipophilicity indices from isotropic solvent systems and from anisotropic membrane-like systems are discussed for their capacity to predict passive drug permeation across biological membranes such as the intestinal epithelium, the blood-brain barrier (BBB) or the skin. The broad evidence presented here shows that beyond the predictive power of lipophilicity parameters, the various intermolecular forces they encode allow a mechanistic interpretation of passive drug permeation.

It is quite common for the same material to crystallize in different arrangements of the molecules in the crystal. This phenomenon is referred to as polymorphism and it happens for elements, pharmaceuticals, biological compounds and proteins. In this article we present a brief review of polymorphism, stressing its physical aspects, types and applications. We discuss why it is important to understand the phenomenon, and the need to develop ways of controlling it. We also outline some legal issues related to it.

Fourier transform ion cyclotron resonance mass spectrometry, combined with modern ionization (fast atom bombardment , electrospray ionization, matrix-assisted laser desorption–ionization), fragmentation (collision-induced dissociation, surface-induced dissociation, one-photon ultraviolet photodissociation, infrared multiphoton dissociation, blackbody infrared radiative dissociation, electron-capture dissociation), and separation (high-performance liquid chromatography, liquid chromatography, capillary electrophoresis) techniques is now becoming one of the most attractive and frequently used instrumental platforms for gas-phase studies of biomolecules such as amino acids, bioamines, peptides, polypeptides, proteins, nucleobases, nucleosides, nucleotides, polynucleotides, nucleic acids, saccharides, polysaccharides, etc. Since it gives the possibilities to trap the ions from a few seconds up to thousands of seconds, it is often applied to study ion/molecule reactions in the gas phase, particularly proton-transfer reactions which provide important information on acid–base properties. These properties determine in part the three-dimensional structure of biomolecules, most of their intramolecular and intermolecular interactions, and consequently their biological activity. They also indicate the form (unionized, zwitterionic, protonated, or deprotonated) which the biomolecule may take in a nonpolar environment. Figure Biomolecules in the gas-phase acidity-basicity scale