Disposition isomers

Keywords Chemical orbital theory, Cw-stability, Cyclic conjugation. Disposition isomers. Diradicals, Donor-acceptor, Electron delocalization, Geminal bond participation, Inorganic heterocycles. Ring strain. Orbital phase. Orbital phase continuity. Polarization, Preferential branching. Reactivity, Selectivity, Stability, Tautomerism, Z-selectivity... 

X-ray crystallographic analyses demonstrate that, in the solid state, Zr- and Ti-FI catalysts 1 and 2 possess approximately octahedrally coordinated metal centers and C2 symmetry, with a trans-O, cis-N, and cis-C 1 disposition (isomer A) (Fig. 11). 

Three-dimensional (3-D) descriptors of molecules quantify their shape, size, and other structural characteristics which arise out of the 3-D disposition and orientation of atoms and functional groups of molecules in space. A special class of 3-D indices is quantitative descriptors of chirality. If a molecule has one or more chiral centers, the spatial disposition of atoms can produce enantiomers, many of which will have the same magnitude of calculated and experimental physicochemical properties having, at the same time, distinct bioactivity profiles. Basak and coworkers [22] have developed quantitative chirality indices to discriminate such isomers according to their structural invariants which are based on the Cahn-Ingold-Prelog (CIP) rules. 

During preclinical assessment of an enantiometric mixture, it may be important to determine to which of these three classes it belongs. The pharmacological and toxicological properties of the individual isomers should be characterized. The pharmacokinetic profile of each isomer should be characterized in animal models with regard to disposition and interconversion. It is not at all unusual for each enantiomer to have a completely different pharmacokinetic behavior. 

On account of this overlap there is considerable resistance to rotation about a double bond and it produces a rigid molecule, hi other words the disposition of groups attached to the carbon atom can be shown in different ways in space, giving rise to isomers. Therefore geometrical isomerism is a consequence of restricted rotation about double bonds. 

The majority of scientific and governmental concerns for the hazards of these compounds have been directed toward analytical methodologies, toxicology, epidemiology and determination of the disposition in the environment of the single most toxic isomer, 2,3,7,8-tctrachlorodibenzo-p-dioxin [77-82, 84],... 

Johnson JD, Isom GE. 1985. The oxidative disposition of potassium cyanide in mice. Toxicology 37 215-224. 

The third class of stereoisomers is diastereomers. One class of diastereomers arises from the disposition of equivalent groups on carbon-carbon double bonds. If the two groups are on the same side of the double bond, we refer to the isomer as cis if they are on opposite sides, we refer to the isomer as trans. These diastereomers have different physical, chemical, and, frequently, biological properties. Examples that we have seen include the female silkworm moth sex attractant (bombykol), the sex attractants of the brown algae, and the trail pheromones of ants. 

The importance of chiral factors in disposition and toxicity has been fully recognized only relatively recently, although important examples have been known for some time. For instance the S(—) enantiomer of thalidomide is known to have greater embryotoxicity than the R(+) enantiomer (see chap. 7). Another example in which a particular isomer of a metabolite is responsible for a carcinogenic effect is the exo-oxide of aflatoxin Bi, discussed later in this chapter (Fig 5.14). 

The structural indices of aromaticity, I, of oxadiazoles (145-148), thiadiazoles (150-153) and selenadiazoles (155, 156) are compared with that of the parent furan (144), thiophene (149) and selenophene (154) (Scheme 11). 1,2,3-Oxadiazole (145) is the least stable among them since all attempts to synthesize this compound were unsuccessful, most likely because of its easy isomerization to the acyclic isomer. At the same time its sulfur analogue (150) possesses good stability and has been synthesized. Its 2,4-diaza- (151), 3,4-diaza- (152) and 2,5-diaza-(153) isomers demonstrate even more the extent of n-electron delocalization. There exists a well-known tendency of decreasing aromaticity depending on the type of pyrrole-like heteroatom S > Se > O. However, there is no uniformity in the change in aromaticity in the horizontal rows, i. e., dependence on heteroatom disposition. 

The conformational aspects of cis- and frans-4-alkyl-3-phenyl-3,4-dihydrocoumarins have been studied with the conclusion that for both of the isomers (59) and (60) an axial disposition of the 3-phenyl group is preferred (75MI22200). 

Analysis of the 13C chemical shifts of C-2 and C-6 in a series of 2-substituted 6-methoxy-3,6-dihydropyran-3-ones (82) allows the assignment of configuration to the isomeric pairs. C-2 is shielded by ca. 5 p.p.m. and C-6 by ca. 2.5 p.p.m. in the trans isomer compared with the corresponding signals of the cis compound (79MI22200). The upheld shift is associated with the 1,3-diaxial disposition of the substituent and the proton on the y-carbon atom. This y-effect has also been noted in the dihydropyran ring system (74MI22200). 

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