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Friday, December 10, 2010

How many hydrogen-bond acceptor groups does triazole have?

Andrew asked me about the H-bond donor capabilities of 1,2,4-triazole:


Apparently, the way he uses the CDK library, it returns zero H-bond donor groups, as is visible in his application down the bottom of the page. When start from the PubChem entry, it correctly detects on H-bond donor group, so it seems to have to do with implicit hydrogens (not uncommon). Debugging will continue later, when I am done analyzing the Beilstein Journal of Organic Chemistry literature with Oscar.

But, I do like to put this question out in the open: how many H-bond acceptor groups does this triazole have? The CDK calculates 3 groups, while PubChem counts 2. ChemSpider thinks 3 too.

Intuitively, I would agree with the CDK and ChemSpider: the nitrogen which acts as the single H-bond donor still have a free electron pair. What do you think? Is PubChem wrong, or is the CDK and ChemSpider wrong? Can this special nitrogen be both a donor and acceptor at the same time? I think so. However, I do not know how I can easily search CrystalEye for this. Bonus points for answering the Blue Obelisk eXchange question.

10 comments:

  1. I vote for 2. Isn't that lone pair busy being part of the PI system?

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  2. Noel beat me to it :) This is a standard question in my organic class - this molecule is aromatic by using the N lone pair - so 2 acceptors is definitely the answer

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  3. Just tried on 2 other softwares: Pipeline Pilot has 2, while Stardrop 3. Note that PP considers the hydrogen explicitly (displayed, and the smiles is c1nc[nH]n1), and it counts 1 donor.

    For chemspider, the ACD is the first one, but the chemaxon tab it counts 3 acceptors and 0 donor as well, as the H disappears.

    Simple example where calculations can "fail".

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  4. 2 h-bond acceptors and 1 h-bond donor.

    BTW: "Debugging will continue later, when I am done analyzing the Beilstein Journal of Organic Chemistry literature with Oscar." Sounds like an excellent study. I've been wanting to try some things with Oscar, so if you could give a step-by-step for a noob to get started, that could be helpful.

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  5. Rich, follow these two links:

    http://chem-bla-ics.blogspot.com/2010/11/installing-oscar.html
    http://chem-bla-ics.blogspot.com/2010/11/oscar4-command-line-utilities.html

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  6. Jérémy, indeed! But I had not realized that variance between toolkits for a simple descriptor like this was so large :)

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  7. Andy and I really appreciate all your efforts to resolve this issue because it is key to the development of useful practical application of our solubility models

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  8. I wish I had a bit more resources, because I really like the solubility project...

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  9. Hi,
    just two comments,

    1) do not use crooked SMILES flying around the internets, SDF is better.

    2) ChemAxon Marvin puts out:
    Donor sites = 1
    Donor count = 1
    Acceptor sites = 2
    Acceptor count = 2

    and on top one can see the microspecies distribution and possible changes during pH.

    I really like that feature. Its not always obvious or intuitive to guess, especially if it goes towards aromatic tautomerism.

    BTW: WDIs CACTVS system can calculate values based on implicit or explicit hydrogen encoding.

    Cheers
    Tobias

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