What does a high logP value mean?

What does a high logP value mean?

A negative value for logP means the compound has a higher affinity for the aqueous phase (it is more hydrophilic); when logP = 0 the compound is equally partitioned between the lipid and aqueous phases; a positive value for logP denotes a higher concentration in the lipid phase (i.e., the compound is more lipophilic).

What is substituent hydrophobicity constant?

The substituent hydrophobicity constant is a measure of how hydrophobic a substituent is, relative to hydrogen. A positive value of π indicates that the substituent is more hydrophobic then hydrogen. A negative value indicates that the substituent is less hydrophobic.

What does highly lipophilic mean?

Lipophilic or ‘lipid-loving’ molecules are attracted to lipids. A substance is lipophilic if it is able to dissolve much more easily in lipid (a class of oily organic compounds) than in water. Source: GreenFacts.

What does log p tell you about a drug?

Lipophilicity is a valuable parameter of the drug which affects its activity in the human body. The Log P value of the compound indicates the permeability of the drugs to reach the target tissue in the body.

What does LogP show?

Lipophilicity, most commonly referred to as the LogP, represents the ratio at equilibrium of the concentration of a compound between two phases, an oil and a liquid phase (Bohnert and Prakash, 2012).

Why is lipophilicity important?

Lipophilicity is an important physicochemical parameter that contributes to the absorption, distribution, metabolism, excretion, and toxicity of a drug. This, in turn, affects the solubility and permeability of a drug and contributes to its potency and selectivity.

What is substituent constant?

The substituent constant is a measure of the total polar effect exerted by substituent X (relative to no substituent) on the reaction centre. Electron-withdrawing m-NO2 ( = +0.71) increases stability of tetrahedral intermediate compared to electron- donating m-CH3 ( = -0.07).

What is the Hansch equation?

An equation relating the differences in the partitions of variously substituted compounds between an organic and an aqueous phase to the hydrophobicity constant, π of the substituent.

How does lipophilicity affect ADME?

On the molecular level, drug lipophilicity affects drug transport through lipid cell membranes as well as drug’s interactions with target protein(s). On the organism level, lipophilicity influences several ADME properties, like absorption, distribution into tissues, binding efficiency of a drug, etc.

What does a high polar surface area mean?

Molecules with a polar surface area of greater than 140 angstroms squared tend to be poor at permeating cell membranes. For molecules to penetrate the blood–brain barrier (and thus act on receptors in the central nervous system), a PSA less than 90 angstroms squared is usually needed.

What does a negative log D mean?

Negative values of logD (-1.44 to 0) in the physiologically relevant pH range (pH 1–8) lead us to conclude that this compound would be more susceptible to higher aqueous solubility and of lower lipophilicity in the body. As a result we would expect membrane permeability to be poor.

What is the difference between LogP and log D?

Log D is a distribution coefficient widely used to measure the lipophilicity of ionizable compounds, where the partition is a function of the pH. For non-ionizable compounds Log P = Log D throughout pH range, whereas for ionizable compounds Log D takes into account the partition of both ionized and non-ionized forms.

How is the hydrophobicity constant of a parabolic curve calculated?

For parabolic curve Log 1/C = -k (logp)2 + k2 logp + k3 •The substituent hydrophobicity constant (π) πx = logpx – logph Ph= partition coefficient of std compound Px= partition coefficient for std with substituent b) Steric Effect The bulk, size and shape of drug will influence how easily it can approach and interact with binding site.

Why is hydrophobicity important in the HIC process?

There is evidence that the hydrophobicity characteristics provided by IAM columns are better suited for modeling the pharmacokinetics of drug processes. The hydrophobicity of the biomolecules is a parameter of great importance for selection of the best operating conditions for an HIC process.

Which is the most common measure of hydrophobicity?

Octanol–water is a reference system that provides the most commonly recognized hydrophobicity measure: the logarithm of the partition coefficient, log P. The standard ‘shake-flask’ method for determining partition coefficients in liquid–liquid systems has several disadvantages.

What are the limitations of a Hansch analysis?

Limitations of Hansch analysis • 1. There must be parameter values available for the substituent’s in the data set • 2. A large number of compounds is required. • 3. Depends on biological results (Chance of error) • 4. Interrelationship of parameters • 5.