Chemistry Reference
In-Depth Information
In the guanine molecule (number of chemical bonds
N
= 12), according to
Table 4.1, there are only two nonempty categories (single and aromatic) of chemical
bonds (
k
= 2). These categories include 2 and 10 bonds, respectively. Consequently,
the value of SE
bonds
is
SE
bonds
= −[2/12 · Ln (2/12) + 10/12 · Ln (10/12)] ~ 0.4506.
In guanine, the diversity of chemical bonds (from the point of view of bond
orders) is much smaller than the diversity of atoms (from the point of view of
atomic numbers). In addition, one can say that the amide chemical group in gua-
nine seems to be nonexistent because the bond order of the C-N bond is too small
(
Figure 4.4
)
.
Putting the values of many descriptors (net charges, geometric distances, features
of molecular fragments, etc.) into categories is a difficult task. In contrast, it is easy
to put the features of kenographs into categories.
4.3.13 p
artition
c
oeFFicient
in
o
ctanol
-W
ater
s
ysteM
A pure substance, dissolved in a heterogeneous system consisting of water and a
nonmiscible solvent, is characterized, at equilibrium, by the concentration c
1
in water
and the concentration c
2
in solvent. When the concentrations c
1
and c
2
are much lower
than the solubilities (the maximum concentrations at working temperatures), the par-
tition coefficient is defined as the ratio P = c
2
/c
1
.
There are numerous experimental methods for determining the P value for
organic substances (de Bruijn et al. 1989; Tayar et al. 1991). Since experimentally P
values are within a very broad range, the logarithm of P is used instead. The LogP
descriptor is, by definition, a measure of the lipophilic nature of the molecules
that make up the dissolved organic compound. Sometimes there is a high statisti-
cal correlation between biochemical activity and the LogP values and/or of the
values of the parabola
a
+
b
· LogP +
c
· (LogP)
2
. It was found that the best results
are obtained when the organic solvent is
n
-octanol, perhaps because the octanol-
water system is a better model for the characteristics of the biophase. Therefore,
calculated or experimentally derived LogP in the octanol-water system is the most
utilized descriptor.
It is believed that a strong lipophilic character (high LogP value) reflects a high
capacity of the molecule to pass through cell membranes. On the other hand, the
finding that a pronounced lipophilic character is not an obstacle in the transport
of molecules to the target cells is explained by the assumption that, in the aqueous
blood environment, the bioactive molecules form heterogeneous microemulsions or
microsuspensions, not homogeneous solutions.
The development of an algorithm for calculating the LogP value is a difficult task,
because terms such as
functional group
(Tarko 2004a),
conjugation
,
position in the
carbon chain
, and
proximity effect
are difficult to express mathematically. Some
software considers LogP an additive property (Hansch et al. 1968; Hansch and Leo,
1979; Rekker and Nys 1974; Rekker and de Kort 1979), but others calculate LogP
as a function of descriptors correlated strongly with LogP (Gaillard et al. 1994).
