Chemistry Reference
In-Depth Information
The ACD/LogP algorithm (ACD/LogP
®
) considers numerous types of carbon atoms
(relative to hybridization, number of hydrogen atoms attached, the position in the
carbon chain, presence in cycles, and proximity of aromatic cycles), hundreds of
functional groups and thousands of pairs of neighboring functional groups. In addi-
tion, the ACD/LogP algorithm proposes a formula for calculating the solubility in
water, depending on the melting point and calculated LogP value of the molecule of
interest.
The calculation of LogP is inaccurate when the value of the denominator and/or
the numerator in the c
2
/c
1
ratio is very large or very small. Examples include octa-
nol (c
2
~ ∞, c
1
~ 0), macromolecules (c
2
~ 0, c
1
~ 0), perfluorinated compounds (c
2
~ 0,
calculates LogP = −1.05, while for isomer B, one calculates LogP = −0.96.
4.3.14 F
lexiBility
d
escriptors
The possibility of rotation of some groups of atoms around some chemical bonds is
intuitively associated with molecular flexibility. Consequently, the number of rotat-
able bonds and the percentage of rotatable bonds are the simplest descriptors that
measure the molecular flexibility. More complicated formulas calculate flexibility
descriptors by weighting some topological descriptors; therefore, they consider the
shape and size of the molecules, the number of atoms, and the sum of bond orders
(Ta rko 20 0 4c).
lex
1
= W/(N ∙ S)
(4.36)
lex
2
= flex2
1
/(1 + p)
(4.37)
where
W = Wiener topological index
N = number of heavy atoms
S = bond order sum (all bonds which bond heavy atoms)
p = percentage of aromatic bonds (using only bonds that bond two heavy atoms)
Much utilized is the Kier flexibility index (Kier 1990), defined as a weighted
product of some shape indices of the molecules.
K
k
= (N + α − k + 1) · (N + α − k)
2
· (P
k
+ α)
2
(4.38)
where
k is the order of the shape index and has the value 1 or 2; for k > 2, Kier proposes
formulas different from (4.38)
N is the number of atoms in the molecule
P
k
is the number of topological routes, of length equal to k steps, that can be taken
on the graph of the molecule; P
1
(k = 1) is the number of chemical bonds in
the molecule
α is the sum after N α = ri
C
Σ r
i
