Tris[2-(dimethylamino)ethyl]- amine' protonated atoms

Hi,

I'm working with the molecule tris[2-(dimethylamino)ethyl]- amine and
I'm trying to find the protonated (nitrogen) atoms of this molecule at
pH 7.4. 



tris[2-(dimethylamino)ethyl]- amine has 4 H bond acceptors
(www.chemspider.com).  And based on the micro pKa values calculated with
the pKa calculator (9.11, 9.06, 9.11, 9.11), one would expect all four
nitrogen atoms to be listed as major microspecies at pH 7.4.  However,
this is not the case as only three of the nitrogen atoms are listed as
major microspecies at pH 7.4. 



The results for the major microspecies at pH 7.4 seems to correlate to
the results obtained for the macro pKa values: 9.00, -1.36, 9.70, 8.63. 
The pKa value of -1.36 seems very low.  Are these results correct or
are these a consequence of some fine-tuning issue of the pKa algorithm
when dealing with multiple ionization sites?  If so, is there a way
around it? 



For our research studies it is crucial that we can rely on the accuracy
of the output from the ChemAxon pKa calculator.  That's why we are
requesting assistance in finding out the reason for the large difference
in the pKa values and in tuning the pKa calculation algorithm used by
the pKa calculator (if applicable).



Thanks in advance,

Adriana

Hi,

First of all , our caclulation is correct. Only three "N" atoms will be protonated at pH=7.4.   I have checked the pKa of certain similar compounds.  The very low "4th" pKa (-1.36) value  seems to be reasonable in our pKa calculation.

The amount of the fully protonated  "tetra-cationic"  form will be extremly low at pH=7.4. 

Jozsi

Hi Jozsi,

Thanks for the reply!

You mentioned that the low pKa (-1.36) seems reasonable.  However, the same atom is getting a micropKa of 9.06.  Why are these values so different?

Thanks,

Adriana

Hi,

The "intrinsic" pKa and the "apparent" pKa  usually significantly different in case of multiprotic molecules.

This is the situation now with the :"tetra protic" basic compounds.

Jozsi

Thanks!

The intrinsic pKa changes from microspecies to microspecies.  How can I know which microspecies was used by the pKa calculator when calculating the intrinsic pKa?

Hi,

How can I know which microspecies was used by the pKa calculator when calculating the intrinsic pKa? 

An  "intrinsic" pKa value calculated from   a  submitted microspecies   without changing its protonation state.

The "apparent" pKa value calculated from a set of microspecies which are known only inside the pKa calculator.

 

Jozsi

Hi,

Thanks for the reply.

1.  I'm a bit confused about the explanation above for the "intrinsic" pKa ("An  "intrinsic" pKa value calculated from   a  submitted microspecies   without changing its protonation state.").  Could you please explain this in more detail?

2.  I'm trying to find what atoms are protonated at pH 7.4.  Should I be looking at the "intrinsic" or "apparent" pKa and why?  (As you mentioned before, these values are very different for multiprotic molecules.

Thanks in advance.

 

 Hi,

1.  ....Could you please explain this in more detail? 

8 microspecies can be submitted to the pKa calculator. I sketched them on the "mszp1.png".

Their intrinsic pKa can be calculated after setting the "micro" pKa mode" on the pKa option panel.
The pKa option panel and the calculated intrinsic pKa values are on the "mszp2.png".

2.  I'm trying to find what atoms are protonated at pH 7.4.  Should I be looking at the "intrinsic" or "apparent" pKa and why?  (As you mentioned before, these values are very different for multiprotic molecules. 

Just simple choose any one of  the 8 microspecies. Set the "macro" pKa mode on the pKa option panel.

Results of the pKa calculation given on the "mszp3.png". 

6 microspecies have significant quantity in  the pH=0-14 range.

The amount  of the protonated microspecies in the  pH=0...pH=14 range  can be checked from the "pH-distribution".E.g.   at pH=7.4, the  three terminal "N" atoms are protonated and this form will be present up to 94%.      

  

Jozsi  

Hi Jozsi,

Thank you for the detailed information!

What ionic strength and dielectric constant for the medium is the pKa calculator using when I select 'macro pKa' to calculate the "apparent" pKa (in order to find what atoms are protonated at pH 7.4)?  My understanding  the "apparent" pKa is dependent of experimental conditions such as the ionic strenght and polarizability of the medium.

Thanks,

Hi,

The aqueous pKa values are calculated and the ionic strength is not available as an adjustable parameter. The calculated pKa values are considered to be thermodynamic ones  which are extrapolated to  zero ionic strength.    

Jozsi

Thanks!