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Chemistry Forums for Students => Organic Chemistry Forum => Topic started by: whitecoatblackhat on March 06, 2021, 11:30:04 PM

Title: Adenosine (Pure Anhydrous) Solubility
Post by: whitecoatblackhat on March 06, 2021, 11:30:04 PM
Fellow Chemists,

I'm trying to dissolve pure Adenosine powder, not AMP, ADP or ATP.

However, I can't find a vehicle that allows me to dissolve higher concentrations of Adenosine.

I don't want to introduce heat into the equation because I need the adenosine to stay dissolved at room temperature.

Heating up the vehicle is only a temporary solution.

The most distilled water can dissolve is 300-350mg of adenosine anhydrous per 100 ml of water.

Ethanol doesn't work.

Propylene Glycol and peg 40 hydrogenated solubility aren't efficient solubilizers as well.

And I don't want to use DMSO.

Any other suggestions?

All will be highly appreciated!

Thank you!
Title: Re: Adenosine (Pure Anhydrous) Solubility
Post by: AWK on March 07, 2021, 02:35:19 AM
This is the solubility of adenosine at ~RT.
Title: Re: Adenosine (Pure Anhydrous) Solubility
Post by: rolnor on March 07, 2021, 03:16:18 AM
Methanol?
Title: Re: Adenosine (Pure Anhydrous) Solubility
Post by: whitecoatblackhat on March 07, 2021, 03:22:31 AM
This is the solubility of adenosine at ~RT.

Sorry, what do you mean by that?

That's the solubility of adenosine at room temperature, in water?

Isn't that what I just wrote above?

Not sure, what you meant by this comment, but thanks for taking the time to reply!
Title: Re: Adenosine (Pure Anhydrous) Solubility
Post by: whitecoatblackhat on March 07, 2021, 03:23:52 AM
Methanol?

Yeah, methanol would be a great vehicle but I'm going to apply the Adenosine solution to my research subject's skin.

Hence, methanol (similar to DMSO) is definitely not suitable.

Thanks for the input!
Title: Re: Adenosine (Pure Anhydrous) Solubility
Post by: AWK on March 07, 2021, 03:28:13 AM
More adenosine will not dissolve in the water. In alcohol, adenosine dissolves even less.
Title: Re: Adenosine (Pure Anhydrous) Solubility
Post by: whitecoatblackhat on March 07, 2021, 03:31:06 AM
More adenosine will not dissolve in the water. In alcohol, adenosine dissolves even less.

Thanks for replying, but you're definitely not carefully reading my question.

You're literally repeating what I just said in my post.

Please, read it again.

My question was not how to dissolve more adenosine in water.

My question was what is a better vehicle for adenosine than water.

Thanks
Title: Re: Adenosine (Pure Anhydrous) Solubility
Post by: AWK on March 07, 2021, 03:47:23 AM
Rather, you don't understand the essence of solubility.
Polar compounds (and such is adenosine) dissolve better in polar solvents (and such is water).
In Pharmacy (rather topically) DMSO is sometimes used (in which adenosine dissolves better).
And those are probably all options.
Title: Re: Adenosine (Pure Anhydrous) Solubility
Post by: AWK on March 07, 2021, 04:04:29 AM
The solubility of adenosine in 1M HCl is about 5 g/100 ml.
Title: Re: Adenosine (Pure Anhydrous) Solubility
Post by: whitecoatblackhat on March 07, 2021, 04:12:45 AM
Rather, you don't understand the essence of solubility.
Polar compounds (and such is adenosine) dissolve better in polar solvents (and such is water).
In Pharmacy (rather topically) DMSO is sometimes used (in which adenosine dissolves better).
And those are probably all options.

Thanks for the reply. I'm very aware of the basic principles of solubility.

I honestly don't understand why we're even discussing this.

I clearly stated that I'm looking for other vehicles that can possibly solubilize pure anhydrous adenosine.

@rolnor Got it immediately and proposed a potential solvent, i.e. methanol (which is exactly what I asked for).

But you simply keep repeating what I said in my original post.

Also, there are many proprietary solvents like TrichoSol, which clearly you aren't aware of because you think that DMSO is the end all be all.

TrichoSol doesn't work in my case and that's why I'm posting a question here.

To gather ideas for other such solvents, be it proprietary or not.

Most importantly, there's clinical data in which adenosine is dissolved at 0.75% and is applied topically on the scalp for the treatment of androgenic alopecia, however, the methods of preparation aren't specified.

They surely aren't applying DMSO or methanol to people's scalps.

This means that there are skin-safe solvents out there that can dissolve adenosine at a higher than 0.30% concentration (which is the highest concentration in water).

Thanks a lot for taking the time to reply, though. I genuinely appreciate your input!

P.S. I did contact the authors of the adenosine 0.75% studies and got no replies.
Title: Re: Adenosine (Pure Anhydrous) Solubility
Post by: rolnor on March 07, 2021, 04:21:40 AM
You dont have many options, very few solvents are possible to apply topical. Maybe glycerol?
Title: Re: Adenosine (Pure Anhydrous) Solubility
Post by: whitecoatblackhat on March 07, 2021, 04:28:30 AM
You dont have many options, very few solvents are possible to apply topical. Maybe glycerol?

Interesting. Thanks for the suggestion!

I can't find any data on the solubility of adenosine in glycerol but I might buy some and try it myself.
Title: Re: Adenosine (Pure Anhydrous) Solubility
Post by: AWK on March 07, 2021, 05:05:32 AM
There are clever solutions to this problem (stabilized supersaturated solutions - up to 2%) but they are outside the scope of this Forum. Search in patents.
Title: Re: Adenosine (Pure Anhydrous) Solubility
Post by: rolnor on March 07, 2021, 06:17:23 AM
So its hair-loss we are talking about?
https://rarediseases.info.nih.gov/diseases/9269/androgenetic-alopecia

I really wonder if adenosine is better than Minoxidil etc. This is a well studied problem, I think you will have more luck with the standard treatment even though it is expensive.
Title: Re: Adenosine (Pure Anhydrous) Solubility
Post by: whitecoatblackhat on March 07, 2021, 11:32:39 PM
There are clever solutions to this problem (stabilized supersaturated solutions - up to 2%) but they are outside the scope of this Forum. Search in patents.

This is the info I was looking for! Great stuff! Thanks!

Do you mean that you know of certain ways to create a supersaturated solution that can dissolve adenosine up to 2%?

Thanks!
Title: Re: Adenosine (Pure Anhydrous) Solubility
Post by: whitecoatblackhat on March 07, 2021, 11:36:35 PM
So its hair-loss we are talking about?
https://rarediseases.info.nih.gov/diseases/9269/androgenetic-alopecia

I really wonder if adenosine is better than Minoxidil etc. This is a well studied problem, I think you will have more luck with the standard treatment even though it is expensive.

Yes, I've been studying the pathology of androgenic alopecia for 5+ years.

I've researched minoxidil extensively. It's an old, palaeolithic drug that comes with a myriad of side-effects, ranging from mild to life-threatening.

That's why we're researching other potential topical hair growth agonists, that have at least some merit.

One such is adenosine.

Thanks!
Title: Re: Adenosine (Pure Anhydrous) Solubility
Post by: rolnor on March 08, 2021, 12:45:16 AM
If you are this serious in your work it is surprising that you not have checked the patent literature before posting you question here, are you doing this proffessionally or more as a hobby? Minoxidil does not help everybody with hair-loss but I can bet some money that it is more efficient than adenosin, do you have a reference supporting that adenosin is better than minoxidil?
Title: Re: Adenosine (Pure Anhydrous) Solubility
Post by: Babcock_Hall on March 08, 2021, 10:36:49 AM
This is a bit of a tangent, but I would not use a mineral acid in an attempt to increase solubility for almost any application.  One will hydrolyze the N-glycosidic bond.
Title: Re: Adenosine (Pure Anhydrous) Solubility
Post by: whitecoatblackhat on March 09, 2021, 10:19:53 AM
If you are this serious in your work it is surprising that you not have checked the patent literature before posting you question here, are you doing this proffessionally or more as a hobby? Minoxidil does not help everybody with hair-loss but I can bet some money that it is more efficient than adenosin, do you have a reference supporting that adenosin is better than minoxidil?

I'm doing this professionally.

I never said that adenosine is better and more effective than minoxidil. Please, show me where I've said that.

Minoxidil is the most powerful hair growth agonist on the market today. That's non-negotiable.

It's by far stronger than adenosine.

However, there are a plethora of side-effects that come with minoxidil, ranging from surface-level side effects to life-threatening ones.

And many people avoid using it because of that.

For this reason, we're looking to develop some other topical hair agonists that don't necessarily rival minoxidil in terms of potency but at least yield some noticeable results whilst having a far better side-effect profile.

Therefore, giving people more choice when it comes to picking a product that stimulates hair growth.

Minoxidil is palaeolithic and we need more innovation in this field.



Title: Re: Adenosine (Pure Anhydrous) Solubility
Post by: whitecoatblackhat on March 09, 2021, 10:20:49 AM
This is a bit of a tangent, but I would not use a mineral acid in an attempt to increase solubility for almost any application.  One will hydrolyze the N-glycosidic bond.

Interesting! That's great advice! I'll look further into this.

Thanks!!
Title: Re: Adenosine (Pure Anhydrous) Solubility
Post by: rolnor on March 09, 2021, 12:46:09 PM
Whitecoat, I am sorry, I jumped to conclusion. How do you test your compounds, do you use some animal-model?
Its a bit confusing because Minoxidil does not work for all, so if you have something (like adenosine) thats even less efficient, how do you measure the effect?
Title: Re: Adenosine (Pure Anhydrous) Solubility
Post by: rolnor on March 09, 2021, 02:36:54 PM
I am wondering, how can Minoxidil be so toxic? Its an overthecounter drug?
Title: Re: Adenosine (Pure Anhydrous) Solubility
Post by: MOTOBALL on March 09, 2021, 06:21:18 PM
Are there any non-toxic ionic liquids?

Regards,
Motoball
Title: Re: Adenosine (Pure Anhydrous) Solubility
Post by: MOTOBALL on March 09, 2021, 10:55:14 PM
Whitecoat,

Have you seen the use of solid dispersions of a a drug with e.g. sucrose to enhance aqueous solubility of an API?

Also, use amorphous rather than crystalline adenosine.

Regards,
Motoball
Title: Re: Adenosine (Pure Anhydrous) Solubility
Post by: whitecoatblackhat on March 10, 2021, 03:59:50 AM
Whitecoat, I am sorry, I jumped to conclusion. How do you test your compounds, do you use some animal-model?
Its a bit confusing because Minoxidil does not work for all, so if you have something (like adenosine) thats even less efficient, how do you measure the effect?

No problems, we're doing very small-scale in vitro testing and it isn't as comprehensive as the previous studies done on adenosine:

https://pubmed.ncbi.nlm.nih.gov/24183218/

https://pubmed.ncbi.nlm.nih.gov/26508659/

I would like us to get a phototrichogram in the very near future to produce the most accurate assessments possible.

But for now, we're just using generic camera photos.

I believe one of the factors for adenosine being less efficient than minoxidil is its poor solubility.

Minoxidil 5% beats adenosine 0.75% every single time.

But if you compound a Minoxidil 0.75% solution, it's not gonna be that much better than 0.75% adenosine.

That's why I'm trying to find a way to increase the concentration of adenosine to at least 2% and see if that's comparable to 2% minoxidil.

Title: Re: Adenosine (Pure Anhydrous) Solubility
Post by: whitecoatblackhat on March 10, 2021, 04:10:38 AM
I am wondering, how can Minoxidil be so toxic? Its an overthecounter drug?

I never said minoxidil is toxic. I just said that it has a plethora of side effects.

Minoxidil was first compounded as an anti-hypertensive drug known as Loniten.

And the hypertrichosis was actually a side-effect of oral minoxidil.

So, then the researchers decided to create a topical form of minoxidil and see if that can have a localised hair growing effect while minimising the systemic side effects.

To this day, it's not fully understood how minoxidil actually promotes hair growth. It could be a mixture of vasodilation, potassium channel opening, PGE2 upregulation and even having a very mild anti-androgenic effect.

Minoxidil isn't toxic, the side effects are due to the drug going systemic for some individuals.

It is a small molecule with a low molecular weight (~209 daltons).

Therefore, it can easily go systemic for some people.



 

Title: Re: Adenosine (Pure Anhydrous) Solubility
Post by: whitecoatblackhat on March 10, 2021, 04:18:54 AM
Whitecoat,

Have you seen the use of solid dispersions of a drug with e.g. sucrose to enhance aqueous solubility of an API?

Also, use amorphous rather than crystalline adenosine.

Regards,
Motoball

That's what I'm looking for as well, i.e. non-toxic ionic liquids.

Unfortunately, my manufacturer only sells crystalline adenosine.

I'm on the lookout for other versions.

I haven't heard of enhancing the aqueous solubility of an API with things like surcose.

But this is really piquing my interest and I'll look further into it.

Things like sucrose are rather benign and could be easily added to hair topicals.

Very cool piece of info! Thanks so much for that!



Title: Re: Adenosine (Pure Anhydrous) Solubility
Post by: rolnor on March 10, 2021, 08:58:25 AM
Interesting, I still dont see how this can be a non-prescription drug if some get so severe side-effects? I have hever seen any warnings or debate in media about this?
Title: Re: Adenosine (Pure Anhydrous) Solubility
Post by: whitecoatblackhat on March 11, 2021, 03:50:36 PM
Interesting, I still dont see how this can be a non-prescription drug if some get so severe side-effects? I have hever seen any warnings or debate in media about this?

Only a few percent of people get severe side effects from minoxidil.

But it's such a widely-used drug that a few percent out of 200 million total users is still plenty of people who get major side effects.

The internet is riddled with anecdotes of people getting heart palpitations, dangerously low blood pressure, drastically increased resting heart rate, edema and more.

Which is what minoxidil was made to do. It's a vasodilator / anti-hypertensive drug.

Therefore, if you have normal or low blood pressure and you use topical minoxidil but a large chunk of that goes systemic, you'll experience these vasodilatory effects and you'll blood pressure will drop even more.

There are many other drugs on the market that have severe side-effects and nobody cares about that.

But at the end of the day, minoxidil helps millions of people and is an extremely potent hair growth stimulant.

I just want to give people more options to choose from.

That's why we're studying adenosine because it does hold some merit.