turn produces a nerve impulse that the brain perceives as vision. Without light, this
cis/trans isomerization would take 1100 years; with light, it occurs in 10–11seconds.
Using the Cahn–Ingold–Prelog sequence rules, Blackwood et al.(1968) designed a
system to allow an unambiguous “absolute” assignment of cis/trans(orsyn/antiin the case
of C==N bonds) isomerism. For instance, the compound CHCl==CBrI cannot be named
unambiguously by the classical rules. However, after the priority of substituents on each
carbon atom is determined (using the sequence rules), the configuration in which the two
substituents of higher priority lie on the same side is called the Z isomer (for zusammen,
meaning “together” in German). The configuration in which these substituents lie on oppo-
site sides is designated as the E isomer (for entgegen, which means “opposite”).
1.5 ELECTRONIC PROPERTIES OF DRUG MOLECULES
The correct geometry, conformation, and stereochemistry of a molecule permit it to
gain access to the receptor microenvironment. However, it is the electronic structure of
the molecule that enables the electrostatic, hydrogen bonding, and other drug–receptor
binding interactions to actually occur. The chemical structure of a drug molecule, its
chemical reactivity, and its ability to interact with receptors ultimately depend on its
electronic structure—the arrangement, nature, and interaction of electrons in the mole-
cule. In general, the effect of electron distribution in organic compounds can be direct
(short range) or indirect (long range).
Direct electronic effectsprimarily concern covalent bonding, which involves the
overlap of electron orbitals. The “strength” of covalent bonds, the interatomic distances
spanned by these bonds, and dissociation constants are all direct consequences of the
nature of covalent electrons. The nonbonding electron pairs of such heteroatoms as
O, N, S, and P also play an important role in drug characteristics. They are the basis of
such noncovalent interactions as hydrogen bonding (which, as already discussed, has a
profound effect on the hydrophilic or lipophilic characteristics of a molecule), charge-
transfer complex formation, and ionic bond formation. In all of these phenomena, the
nonbonding electron pair participates in a donor–acceptor interaction.
Indirect electronic effectsoccur over a longer range than direct effects, requiring no
orbital overlap. Electrostatic ionic interactions fall partly within this category, since the
40 MEDICINAL CHEMISTRY
(1.12)(1.13)