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QSAR (Quantitative Structure Activity Relation-ship) is a multivariate, mathematical relationship between a set of 1D/2D/3D physicochemical properties (descriptors) and any other property of interest, say biological activity.
1. Conformational descriptors
Energy is the energy of the currently selected conformation in the Study Table (it is assumed you have already generated a set of conformations for each model). LowEne is the energy of the most stable conformation in the set of conformations belonging to each molecular model. EPenalty is the difference between Energy and LowEne.
2. Structural descriptors
The available Structural descriptors are, MW Rotlbonds Hbond acceptor Molecular weight Number of rotatable bonds Number of hydrogen bond acceptors
Hbond donor
Poor absorption and permeability are more likely when Lipinskis 5th Rule
3. Electronic descriptors
The following lists of electronic descriptors are available.
Charge Sum of partial charges
Fcharge
Apol
Dipole HOMO LUMO Sr
Pa Ai
i
Polarizability of a molecule is governed by strength with which the nuclear charges control the electrons and prevent their distortion by the applied field.
Dipole properties have been correlated to long-range ligand-receptor recognition and subsequent binding. Pinduced = P=Induced dipolemoment; E=electric field
Highest occupied molecular orbital energy (HOMO) It is the energy (in eV) of the HOMO
When a molecule acts as a Lewis base (an electron pair donor) in bond formation, the electrons are supplied from the molecule's HOMO.
Readiness to donate electrons is reflected in the energy of the HOMO. Molecules with high HOMOs are more able to donate their electrons and are hence relatively reactive compared to molecules with low-lying HOMOs. Thus descriptor HOMO should measure the nucleophilicity of a molecule.
Superdelocalizability (Sr)
An index of reactivity in aromatic hydrocarbons (AH), proposed by Fukui.
Sr ej cjr m
= superdelocalizability at position r = bonding energy coefficient (eigen value) in jth MO = molecular orbital coefficient at position r in jth MO = index of the HOMO
this is a prediction of the height of the transition state barrier at position r, and
the greatest interaction will occur at the site of largest orbital density, that is, largest c2.
Concept of delocalizability - ej
For low-lying levels(LUMO), ej - bonding energy value is large and +ve
Therefore the upper energy levels will dominate the Superdelocalizability term. Summing Sr for all atomic positions of a molecule gives an idea of electrophilicity, which may be used to predict relative reactivity in a series of molecules.
These are typically used to parameterize the Hammett (or Hammett-like) equation for some series of analogs.
(fit to the set of analogs being studied) the rate of different reactions depends on the electron release or withdrawal of the substituents
x refers
Sm, Sp Electronic effect Sigma meta and Sigma para, respectively. +ve values correspond to electron withdrawal ve values to electron release Sigma is generally not appropriate for ortho substituents because of steric interaction with the reaction center. F, R
X O M P X = electron donating or withdrawing groups
When the substituent is conjugated with the reaction center producing through-resonance effects, Decompose of sigma para (Sp) constant into an inductive (polar) part (F) and a resonance part (R)
pi Hydrophobic character. piX = logPX logPH LogP = The partition co-oefficient in Octanol/water medium
HA
Hydrogen bond acceptor.
The molecular refractivity index of a substituent is a combined measure of its size and polarizability.
Sterimol-L
Steric length parameter, measured along the substitution point bond axis.
Sterimol-B1 through B4 Steric distances perpendicular to the bond axis. These define a bounding-box for the substituent and are numbered in ascending size order.
Sterimol-B5
The overall maximum steric distance perpendicular to the bond axis.
5. Thermodynamic descriptors
The following lists of thermodynamic descriptors are available: AlogP Fh2o Foct Hf MolRef Log of the partition coefficient Desolvation free energy for water Desolvation Free Energy for Octanol Heat of formation Molar refractivity
In this atom-based approach, each atom of the molecule is assigned to a particular class, with additive contributions to the total value of logP and molar refractivity.
The values for some functional groups and as well as atoms in a specific environment are:
GROUP
1.CH3 (Methyl-ali) 2.O (Hydroxyl-ali) 3.CH2 (Methylene-ali) 4.CH (Methine-ali) 5.C (t-butyl-ali) 6.N (Nitro) 7.C= (Vinyl) 8.F (ali-single) 9.Cl (ali-single)
FH2O FOCT
0.800 -5.820 0.200 -0.240 -0.720 11.910 -0.330 0.800 -0.940 -0.160 -3.790 -0.520 -0.560 -0.920 11.840 -0.970 1.430 -1.020
Program calculates FH2O and FOct for each molecule Search the molecule for recognizable substituent groups and their bonding patterns Summing the substituent constants contributions for each group that is present in the molecule