HSP Application note #18
Hansen Solubility Parameter (HSP) and Tamiflu
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.
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.
|Zanamivir: Daiichisankyou||Peramivir: Shionogi|
Hansen divided solubility parameter into 3 parts.
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.
Y-MB Properties Estimation
Y-MB break Smiles into correspponding Functional Groups and Estimate various Properties. These estimation schemes are come from Pirika technologies.
Program automatically divid smiles into functional groups and calculate HSP.
For the beginner, "Smilar HSP"or "not Similar" is very hard to determin.
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.
4 medicine's HSP is within this range.
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.
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.
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??
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?
Other topic of Bio Medical
GC data of class 1, class 2 solvents in Q3C:
HSP and Tamiflu Solubility parameter of Tamiflu or other H1N1 antiviral compounds
HSP for Rabbit: How to design eau de Cologne for rabbit. what LD50(skin, rabbit) means.
HSP and logP: logP, logKow, it is just HSP volume.
HSP and Carcinogenicity: SOM(self organization map) analysis of Poly-chlorinated compounds
HSP and Endocrine Disruptor: categorize by SOM.
HSP and AntimicroBial. Sulfa Drugs and other kind of Drugs.
Gall stone solubilizer: How to dissolve Cholesterol base Gall Stone.
Caco-2 cell monolayer apparent Permeability:SOM analysis