LIPOPHILICITY(Logp,Pka,Logd..)

Molecular Lipophilicity Potential | Logp | Pka | Logd

Molecular Lipophilicity Potential
Logp values reflect only the overall lipophilicity of a molecule.This one dimensional parameter contains limited informations and becomes insufficient when topological or stereochemical features of molecules ara analyzed in the context of intermolecular interactions with receptors.
The MLP describe how lipophilicity is distributed all over the different parts of a molecule(lipophilicity maps and determination of hydro and lipophilic regions of a molecule) The average MLP is used to estimate the Logp in octanol/water .
The MLP is defined by considering a molecule S surrounded by non polar or low polarity organic solvent molecules L.
The molecule exert forces on its envirronment that originate its lipophilicity.
The arrangement of the solvent molecules L arround S varies from a random distribution at far distances to an ordered distribution at short distances.
If one assumes the additive character of Logp,a lipophilic fragment(fi>0) will tend to attract the l molecules whereas an hydrophilic fragment(fi<0) will tend to repel the L molecules.

MLP(M)=Sum(fig(di)*
fi =lipophilicity contribution of the atom i
di=distance between the point M and the atom i
g(di)=1/1+di
The fi are compute by the program .They are a function of the atom type,the interactions between hydrophilic groups,the interactions betwween halogens.
The fi values are never constant and are depending of the envirronment

Main Advantages
provides a quantitative 3D description of lipophilicity.
calculate Logp change for different conformations of the molecule.
can be used to study the interactions between molecules(docking).
do not use a fragment database.

Logp

Other Properties
Logp in other solvent
Solubility in water(LogS,S in mg/l)
Permeation through skin
Intestinal Cell Transport
Blood Brain Barrier(LogBB and LogRB)
Bioconcentration factor(LogBCF)
Adsorption coefficient(LogKOC)
Water/Micelle partition (LogKx)
Seiler Indices(DeltaLogp)

PKA
Pka calculations are done using the equations of Taft and Hammett

Logd
The partition coefficient Logp is a constant for the molecule under its neutral form.
The distribution coefficient Logd is an apparent partition coefficient and varies with ph for the molecule under its ionized form.
(ie,In the Ph region where the molecule is unionized,Logd=Logp.) Logd is a function of Logp,Ph and Pka.
The program display the plot Logd=f(Ph),for different molecules with multiprotic centers(pka and Logp),or with multibasic centers (pkb et logp),or with zwitterions.

(Main)