Charge-heteroatom interactions

A nonbonding lone pair on a heteroatom stabilizes a carbocation more than any other interaction. A resonance structure can be drawn in which there is a ir bond between the positively charged heteroatom and the adjacent cationic center. The heteroatom must be directly attached to the electron-deficient C for stabilization to occur if not, destabilizing inductive effects take over. Even if the heteroatom is directly attached, if geometric constraints prevent overlap between the two orbitals, as in the bicyclic carbocation shown, then no stabilization occurs, and inductive effects take over. 

Cyclic compounds containing two S, Se, or Te atoms may display transannular or intramolecular interactions between the two heteroatoms depending on their positions. If a cation radical is generated on one of the heteroatoms, the second heteroatom can interact to stabilize the cation radical, resulting in the formation of a three-electron-bonded cation radical which further oxidizes to give a dication. Such systems joined by two positively charged heteroatoms have attracted considerable interest. The studies in this field have been hampered by the difficulty of their preparation and further by their instability. 

A comparative study on ylide stability as a function of the heteroatom type was carried out by Doering et al. [3,4]. They concluded that the phosphorus and sulfur ylides are the most stable ones. The participation of three-dimensional orbitals in the covalency determines the resonance stabilization of the phosphorus and sulfur ylides [5-8]. The nitrogen ylides are less stable from this point of view. The only stabilization factor involves electrostatic interactions between the two charges localized on adjacent nitrogen and carbon atoms [9]. 

The tendency of the halogens to form chain-like polyanions that are stabilized by delocalization of the negative charge [15,34] is a basic chemical principle. Donor-acceptor interactions between Lewis-acidic Br2 and halide anions, but also with polyhalides acting as Lewis bases, give rise to the formation of a variety of homo and heteroatomic adducts. The maximum number of atoms in these chains increases with the atomic weights... 

Once the protein interaction pattern is translated from Cartesian coordinates into distances from the reactive center of the enzyme and the structure of the ligand has been described with similar fingerprints, both sets of descriptors can be compared [25]. The hydrophobic complementarity, the complementarity of charges and H-bonds for the protein and the substrates are all computed using Carbo similarity indices [26]. The prediction of the site of metabolism (either in CYP or in UGT) is based on the hypothesis that the distance between the reactive center on the protein (iron atom in the heme group or the phosphorous atom in UDP) and the interaction points in the protein cavity (GRID-MIF) should correlate to the distance between the reactive center of the molecule (i.e. positions of hydrogen atoms and heteroatoms) and the position of the different atom types in the molecule [27]. 

The high electrophilicity of the positively charged element can be modified by intramolecular donation from remote donor substituents. This interaction leads to solvent-free cations with coordination numbers for the positively charged element > 3 and to a considerable electron transfer from the donor group to the element. Frequently used donor substituents utilize heteroatoms with lone pairs (e.g. amino, hydrazino, methoxy, carboxy, phosphino, etc.), in many cases in combination with pincer-type topology of the ligand, for the stabilization of the cationic center. These strongly stabilized cations are beyond the scope of this review and instead we will concentrate on few examples where we have weak donors such as CC multiple bonds, which stabilize the electron-deficient element atom. 

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