HSP and logP

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HSPiP

Hansen Solubility Parameter in Practice official HP

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Our concept of Solubility is divid Hildebrand solubility parameter into 3 terms.

dD: dispersion term

dP: polarity term

dH: Hydrogen bonding term

And tread [dD, dP, dH] as 3D vector.

If the vector are similar, it will dissolve each other.

Vectors similarity is determined by HSP distance.

LogP, logKow (Octanol/water partition ratio) is very important index in medical area, so we try to find out the relationship HSP and logP.

We show basic concept in above picture.

If the chemical is relatively easily dissolve to Octanol, HSP distance is small.

And made a lot of QSPR model but failed.

So, we start to examine logP more detail.

We extract only hydrocarbon data of logP and plot of it.

tot HSP = sqrt(dD^2 + dP^2 + dH^2) (vector length)

For plain hydrocarbon’s dP and dH is almost 0, tot HSP is just dD.

With this result shows, if logP becomes large, even though dD is not change so much.

Some cyclic hydrocarbon’s dD become large compare to chain type of hydrocarbon.

Larger hydrocarbon’s logP become larger.

So, from fundamental reason, HSP can not estimate logP.

But when I build QSPR model I notice one thing.

In HSP concept, HSP volume play very important role and we have HSP volume column in Excel file. When I drew figure of QSPR model, I happened to plot logP vs HSP volume.

It have so beautiful correlation logP and HSP Volume.

So, we start to check other compounds.

At first, we extract halogenated compounds logP from our database and plot with HSP volume. It is completely identical with hydrocarbon line.

HSP volume become large according to F<Cl<Br<I.

But you do not need to know nature of F, Cl, Br, I to know logP.

It is governed just by Volume.

This result is very strange for us, because solubility parameter of Halogenated compounds are so different.

But for the logP, fact is that.

And we checked aromatic compounds without functional groups.

For these compounds, logP is just governed by HSP Volume.

For sulfur compounds, thiol compounds are identical with hydrocarbon’s line.

thio-ether compounds make slightly upper line.

(this case, only one sulfur atom)

For only one functional group of alcohol(OH), Ether, Ketone, Aldehyde(ALD) compounds, these make upper line, but shift amount is almost same.

And the slope is identical to hydrocarbon’s line.

This result is also so strange to us.

Alcohol is very easily dissolve to water and Ether is not.

So, at first, we thought alcohol line go much higher line to Ether line.

But from this result, alcohol is very easily dissolve to water but also dissolve to Octanol.

So, the ratio is identical.

And the lines are parallel, that means, one functional group of alcohol, Ether, Ketone, Aldehyde, it reduce HSP volume about 60.

Then the line become identical.

Carboxylic Acid(CA), Carbonate, Ester compounds are almost same with above theory.

we want to note one thing. Cyclic ester especially lactones goes much upper line.

Nitrogen containing compounds are also same with above theory.

Then we want to know multi functional compounds.

For Alcohol, we know one OH group reduce HSP Volume about 60.

And multi OH group case, it become almost same tendency.

You just reduce HSP Volume 60*OH number.

For ester, ether, combination of these functional groups, result is very easy to understand.

And if we determine Reduce Volume amount with using multiple Regression method,

we can get logP estimation scheme.

The result become very beautiful line.

So, we can conclude that logP is just determined by Volume and some functional group reduce Volume certain amount.

logP is not solubility related Index.

If you want to apply logP into permeability, bio-concentration or something, please think these results.

We know some exceptions.

Molecule have both COOH and amine, additivity will not work.

Some compounds that have (-OCH2CH2O)nOH, it will not work.

And more.

Anyway, our HSP solubility parameter method, we deal volume as it is.

And evaluate how materials and compounds interact.

“Like seeks like”

Try HSP if you failed to understand with only logP!!

If you want to try logP calculator, please visit Pirka page

(But calculation routine was developed almost 10 years ago. Very old version)

Newest estimation scheme of logP is implemented in HSPiP ver. 3.