Hansen Solubility Parameter (HSP) and Tamiflu,H1N1 antiviral compounds

HSP Application note #18

Hansen Solubility Parameter (HSP) and Tamiflu

2010.2.9

HSPiP Team Senior Developer, Dr. Hiroshi Yamamoto

Solubility parameter of Tamiflu

On the top page of ChemSpider HP, 4 molecules of H1N1 antiviral compounds are listed.

I am very interested in those compounds, so I calculated Hansen Solubility Parameter (HSP).

Hansen Solubility Parameters (HSP)

Hansen Solubility Parameters(HSP) were developed by Charles M. Hansen as a way of predicting if one material will dissolve in another and form a solution. They are based on the idea that "like dissolves like" where one molecule is defined as being 'like' another if it bonds to itself in a similar way.
Specifically, each molecule is given three Hansen parameters, each generally measured in MPa0.5:
dD:The energy from dispersion bonds between molecules
dP:The energy from dipolar intermolecular force between molecules
dH:The energy from hydrogen bonds between molecules.
These three parameters can be treated as Vector for a point in three dimensions also known as the Hansen space. The nearer two molecules HSP Vector are in this three dimensional space, the more likely they are to dissolve into each other.

What can perhaps be surprising is that one can assign HSP to so many different things. Gases like carbon dioxide, solids like carbon-60, sugar, and biological materials like human skin, depot fat, DNA, and even some proteins all have HSP. The list can be continued with drugs, polymers, plasticizers, and in fact any organic material and even many inorganic materials like salts. The only requirement for an experimental confirmation is that the material must behave differently in a sufficient number of test solvents upon contact.

Pirika JAVA Demo Applet calculate HSP. HSPLight is available here.
Please refer to e-Book of HSPiP if you want know more about HSP.
About the Power Tools that handle HSP more effectively.


	Zanamivir: Daiichisankyou		Peramivir: Shionogi

Hansen divided solubility parameter into 3 parts.
dD: dispersion
dP: polarity
dH: hydrogen bonding
And treat these 3 values as vector.
Basic concept of HSP is similar vector solvent solve similar vector material.
"Like Seeks Like"

I use HSP developer version3 beta3 to calculate HSP.
I only need smiles notation of molecules.

Smiles(Simplified Molecular Input Line Entry Syntax)

SMILES is a string obtained by printing the symbol nodes encountered in a depth-first tree traversal of a chemical graph.
"Organic subset" of B, C, N, O, P, S, F, Cl, Br, and I, brackets can be omitted.
Branches are described with parentheses, as in CCC(=O)O for propionic acid
Double and triple bonds are represented by the symbols '=' and '#'
Ring closure labels are used to indicate connectivity between non-adjacent atoms in the SMILES

Pirika JAVA Demo Applet getting Smiles. Draw2Smiles is available here.
Now we have Power Tool "Draw 2 Smiles", GUI HTML5 software on HSPiP ver. 4.

Y-MB Properties Estimation

Y-MB break Smiles into correspponding Functional Groups and Estimate various Properties. These estimation schemes are come from Pirika technologies.

Pirika JAVA Demo Applet calculate Properties. PirikaLight is available here.
Now we have Power Tool "Y-Predict", GUI HTML5 software on HSPiP ver. 4.

Program automatically divid smiles into functional groups and calculate HSP.

	dD	dP	dH	Volume
1	16.7	7	10	287
2	18.1	10.1	18	220.9
3	17.6	10.4	15.8	249.4
4	17.2	8.3	12.8	270.7
Average	17.4	8.95	14.15	257

2011.4.25
For the beginner, "Smilar HSP"or "not Similar" is very hard to determin.

<p>Please Use HTML5 Browser</p>

Drag=Rotate, Drag+Shift=Larger/Smaller, Drag+Alt or Command(Window key)=Translate.

If you are using HTML5 enable browser such as Chrome, Safari or FireFox (IE9 is out of support), you will see the Canvas. If you pick solvent, solvent name will appear.

The solvent(Blue small sphers) are most widely selected popular slvents. Please check the position of your molecules in this space.

http://www.thedailystar.net/newDesign/swine_flu/news7.php

4 medicine's HSP is within this range.

dD=16.7〜18.1
dP=7〜10.4
dH=10〜18

Hansen Sphere

To determine if the parameters of two molecules (usually a solvent and a polymer) are within range a value called interaction radius (R0) is given to the substance being dissolved. This value determines the radius of the sphere in Hansen space and its center is the three Hansen parameters.

From version 3.1.X, Double Spheres function is available.

Pirika provide JAVA 3D Demo Applet to browse the Sphere(s).
The HTML5 Sphere Viewer examples are available here.
Now we have Power Tool "Sphere Viewer", GUI HTML5 software on HSPiP ver. 4.

I run the search molecule routine from HSPiP database within these range.

HSPiP(Hansen Solubility Parameters in Practice)

The first edition of HSPiP that appeared in November, 2008, greatly enhanced the usefulness of the Hansen solubility parameters (HSP).

The HSP values of over 1200++ chemicals and 500 polymers are provided in convenient electronic format and have been revised and updated using the latest data sources in the second edition (March, 2009).

A third edition of the HSPiP appeared in March, 2010. There are now 10,000 compounds in the HSP file which also includes data on density, melting point, boiling point, critical parameters, Antoine constants and much more. The user is able to carry out many different sorts of optimisations of solubility, evaporation, diffusion, adhesion, create their own datasets (automatically if required) and explore the huge range of applications for HSP in coatings, paints, nanoparticles, cosmetics, pharma, organic photovoltaics and much more.

The 3rd Edition v3.1 was released on 12 December 2010. Current users can upgrade free (now v3.1.09) by downloading the latest .msi installer from http://hansen-solubility.com

The 4th Edition v4.0.x was released on 2 Jan. 2013. The Current users can upgrade with free charge.

2013.1.28 The Visual How to manual of HSPiP. You can understand what HSPiP can do.
Please check the Functional Group List whether your targets are available with HSPiP.
How to purchase HSPiP
2013..1.2 The HSPiP ver. 4 include Power Tools for HSPiP power user.

I got 93 candidates out of 10000 compounds.
The structure is very different, but solubility is similar, I believe.

I show several candidates

The first molecule is Capsaicin.
Hcode 17337 ChemSpider ID 1265957
dD=17.6, dP=7.6, dH=10.9, Volume=290.6

All of my family infected new flu, but I did not yet.
Only I love chili and eat a lot.(I cook myself!)

I want to know the statics.
The difference of infection ratio, who like chili and who do not like chili.

Hcode 17034 　ChemSpider ID 82714
dD=17.4, dP=8.1, dH=10.2, Volume 211.4

This compound is use for fragrance.

Infection ratio of who love this smell, who do not like

Hcode 21360 　ChemSpider ID 9085
dD=18, dP=8.4, dH=12.8, Volume 162.2

This molecule is used for Chinese medicine for cold.
This chemical is extract from Ephedra herb.

Infection ratio of Asian people, who love chinese medicine, who love western medicine.

Hcode 21272 　ChemSpider ID 853
dD=17.2, dP=9, dH=13.3, 　Volume 125.8
This compound is included in Spinach, garlic, green pea.

Infection ratio of who love these food, who do not like.

I can not show other 89 compounds.
Please buy HSPiP and try by yourself.

Today, I read one site and get other molecule for H1N1.
Do you want to know HSP of T-705??

http://organicooking.blog68.fc2.com/blog-entry-5.html

Today's(2010.Feb. 26) news paper, CS-8959 article is putting on.
2nd molecule's dH is 18, so it is a little large.
And this medicine is used with inhale, so it need not much hydroxyl groups.
What it become overall HSP of CS-8958?

Sometime, you want to do this with logP (LogKow).
Please read this article HSP and logP

Today(April. 12th), I read the news paper, it is said, Some Chinese medicine prevent new Flu.

I searched the chemical structure of that Chinese Medicine. Glycyrrhizic acid(from Kanzo)or Hesperidin(from Tinppi). Please compare Hesperidin and Capsaicin.

HSP of Hesperidin become [19.2, 8.4, 15.5]. It is very near to Peramivir: Shionogi .

And also very similar to Ephedrine or Methionine.
So, HSP of natural herbs are so interesting.

please calculate Glycyrrhizic acid by yourself.

2010.9.23 Newspaper in Japan, the virus that does not work Tamiflu, it also does not work Peramivir. HSP of Tamiflu is [16.7, 7, 10] and HSP of Peramivir is [17.2, 8.3, 12.8] so these two is very similar vectors.
But the virus that does not work Tamiflu, still work with Zanamivir [18.1, 10.1, 18].
These two are not similar. So I want to know CS-8958 case.
The basic structure of CS-8958 is near to Zanamivir but HSP is near to Tamiflu.
It is interesting.

Pig contracted both Bird flu and Human flu.
How can we prevent mosquito from animal?

Hansen Solubility Parameters(HSP) Application Notes