Re: [Cdk-devel] [Cdk-user] compound neutralization

[John M. <jo...@eb...>]

Hi Yingfeng,

In short, no. I don’t think it’s easy to provide a comprehensive solution for neutralisation. However approximations such as the RDKit SMARTS you’ve tried offer a good approach for most cases.

What might be easier is to understand why you need to neutralise the compounds?

Anyways, I’m not a chemist but I’ll try my best to answer as to why it’s not simple. Firstly in an InChI string you can tell if there is a charge when a layer starts with /p or /q. 

> InChI=1S/C5H9NO4/c6-3(5(9)10)1-2-4(7)8/h3H,1-2,6H2,(H,7,8)(H,9,10)/p-1/t3-/m0/s1


You could also check the atoms where the formal charge is not 0. I guess what you really mean by charged is whether there is no overall charge.

C[C@@H](O)[C@H]([NH3+])C([O-])=O uncharged
C[C@@H]([O-])[C@H]([NH3+])C([O-])=O charged

Again a simple procedure of summing all the charges in a connected structure will tell you this:

int sum = 0;
for (IAtom a : m.atoms())
    sum += a.getFormalCharge();
boolean charged = sum == 0;

As for neutralising, that’s more tricky. There may be something in a dusty corner of the CDK code but I’m not aware of it. The neutralisation of one atom is easily made by adding/removing protons or breaking/making bonds. However when there are multiple charges it is non-trival as it involves a decision. Considering the example from earlier.

C[C@@H]([O-])[C@H]([NH3+])C([O-])=O charged

how do we decide which neutralised form is correct, these are both have no overall charge:

C[C@@H](O)[C@H]([NH3+])C([O-])=O uncharged
C[C@@H]([O-])[C@H]([NH3+])C(O)=O uncharged

My guess would be the correct way would be to order the neutralisation of charges using pKa? In which case you need a pKa predictor, again, not simple [1].

Neutralisation reduces to finding the ionisation a given pH (i.e. find the pH where the compound is neutral). ChemAxon offer this functionality but I have been told of examples where given two ionisation states of the same compound (one > desired pH, one < desired pH) the tool produces different output. 

Sorry I can’t be of more help.

Thanks,
John

[1] Lee and Crippen, Predicting pKa http://pubs.acs.org/doi/abs/10.1021/ci900209w

On 21 Dec 2013, at 14:05, Yingfeng Wang <ywa...@gm...> wrote:

> I have a compound with Inchi
> 
> InChI=1S/C5H9NO4/c6-3(5(9)10)
> 1-2-4(7)8/h3H,1-2,6H2,(H,7,8)(H,9,10)/p-1/t3-/m0/s1
> 
> First of, is there is a way to know whether it is charged?
> 
> Secondly, is CDK able to neutralize it if it is charged?
> 
> Thanks.
> 
> Yingfeng
> 
> 
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