Problems calculation of acid-pKa and base-pKa values

Hi,


showing the calculation of pKa for NH3 to a professor (who is teaching Basic Chemistry for our first semester students), he said immediately: The pKa for NH4+ is 9.25 !





Of course I know the value 8.86 is the result of an approximate calculation, but it is not named as such in the menu "Tools-Protonation-pKa". This is not evident. In the tool "Elemental Analysis" there are experimental values.





And there are two values for NH3, a value in red 33,62 and one in blue 8.86. What is the meaning of these colors? I couldn't find it in the "Help - - User's Guide".





To make it short. The presentation of these calculated pKa values must be named as those and must be better documented in the User's Guide.





I attach my analysis and my suggestion for documentation.





1st. BTW: There is still a comma between the to values, which makes it difficult to read the values, at least in regions where JAVA uses a comma for decimals. This default has been discussed already in another topic.





2nd. BTW: The possibilty to set the "Decimal places" to more than 2 will be the theme of another topic.





Regards, Hans-Ulrich

Hi,

Quote:

What is the meaning of these colors?

I have attached some PowerPoint slides about the colors.





We are going to supplement the documentation soon.

Quote:

I attach my analysis and my suggestion for documentation.

Zsolt is working on the development of this problem.








Jozsi

Hi Jozsi,


preparing this post I got your answer to my first post in this topic and the attached presentation. I immediately opened the presentation (using OpenOffice on a Linux system) and I tried to analyse it: My first impression is: Why is it so complicated to present the pKa and pKb values of a compound?





Yesterday in a student discussion we used MarvinSketch to evaluate the pKa calculations for water, H2O. We got in analogy to the ammonia example above two values, one in red, 15.7, which is obviously the pKa of water. OK.





But then there was a discussion: What does the blue value -1.8 mean ? From the discussion above and the description in the Marvin User Manual it is the pKa value of the conjugated acid of H2O, i.e. H3O+. I attach our analysis of the H2O example.





My suggestion is: Calculate and present the pKa value for acids and pKb for bases. And these values in different color, with an explanation in the menu !





This would be much easier to understand, and it would be also possible for the acid and base parts of a molecule.





Either use two menu options "pKa" and "pKb" or one option with "pKa / pKb".





Regards, Hans-Ulrich

Hi, there are more problems:





Using the command line program cxcalc a calculation of the pKa values for HCl, H2O and NH3 produces the results in the attached screenshot.





Questions:


1) Why is here for NH3 only one value, in contrast to the GUI results ?


2) What is the meaning of "atoms" ?





"apKa" can be interpreted as "acidic pK acid"-value. OK


"bpKa" can be interpreted as "basic pK acid"-value ? It is obviously the pKa of the conjugated acid to the base b.





Regards, Hans-Ulrich

Hi,

Quote:

Why is it so complicated to present the pKa and pKb values of a compound?

At first sight ,yes, this coloring scheme may seems to be complicated.


I only presented coloring schemes for pKa.


pKb as a measure of the base strength is not used nowadays. It was popular in the old times.





Message of the colors is simple:


The blue pKa is a measure of the base strength, the largest the blue pKa value the stronger the base.





The red pKa is a measure of the acid strength, the smaller the red pKa value the stronger the acid.

Quote:

What does the blue value -1.8 mean ? From the discussion above and the description in the Marvin User Manual it is the pKa value of the conjugated acid of H2O, i.e. H3O+.

Yes, that is correct.

Quote:

1) Why is here for NH3 only one value, in contrast to the GUI results ?

The default range of the calculated pKa is approximately [-10.0, +20.0]. Outside this range the pKa is not calculated. This range can be adjusted in the cxcalc with the "-i" and "-x" optinos.





E.g.: cxcalc pka -x 40 molekula.mol


Both pKa value of ammonia will be appear with this setting.

Quote:

2) What is the meaning of "atoms" ?

Protonation or deprotonation occures on these "atoms".

Quote:

"bpKa" can be interpreted as "basic pK acid"-value ? It is obviously the pKa of the conjugated acid to the base b.

Yes, this is correct.








Jozsi

Hi Jozsi,

Quote:

The default range of the calculated pKa is approximately [-10.0, +20.0]. Outside this range the pKa is not calculated. This range can be adjusted in the cxcalc with the "-i" and "-x" optinos.

I get the result shown in the screenshot.





Regards, Hans-Ulrich

Hi,








Yes, I was able to reproduce.


33.6 is appeared in the GUI window. This value is outside of the required default pKa range.





We check this and fix it asap.





Thanks.





Jozsi

Hi,





now there is the Resonance / Mesomerism problem we already had in Hueckel calculations, see screenshot.


(In Hueckel calculations it is solved).





There is only one species in between (meso) the two resonance formulas, so there cannot be different pKa values.





What's wrong ?





Regards, Hans-Ulrich

Hi,

Quote:

What's wrong ?

Yes this is wrong.





Calculated pKa is not the same because two different conjugated acids assigned to the same basic anion.





Two conjugated acids can exist: vinyl alcohol and acetaldehyde.





Vinyl alcohol is unstable tautomeric form of acetaldehyde and will be converted into acetaldehyde. This is why pKa of CH2=CH-O(-) and pKa of (-)CH2-CH=O will be the same than pKa of acetaldehyde.








Creating of a suitable conjugated acid of ions is not implemented yet. We are going to do this soon.








Jozsi

Hi Jozsi,


your picture above is wrong:





1) The horizontal arrows must belong to chemical reactions, i.e. equivilibriums. The arrows you use concern resonance. This is important!


It is simply chemical nomenclature. Please see also my topic on different arrows in this forum,


http://www.chemaxon.com/forum/ftopic4266.html





2) The vertical red arrow belongs not to resonance structures. These are tautomers, if the formula at the bottom has an hydroxy-group.





3) You *cannot* formulate two different acid/base equivilibriums to a single mesomeric anion.





These structures are in German "Mesomerie-Grenzstrukturen", which means the real species is "meso" (about in the middle) and the "Grenzstrukturen" are only wave-functions for quantum-chemical Valence-Bond handling of molecules.





I had today an intensive discussion about this topic, with professors teaching a lot of courses in basic chemistry not only for chemists but also for biologists, physicists and students in bioinformatics. They agreed intensively to my argumentation and we found another example, now a cationic acid .


I will post it, asap.





Regards, Hans-Ulrich

Hi,





I have attached a new figure. I considered your coments in creating this new figure. Instead of the "common anion" I sketched explicitly the resonance stabilized anions. I have added the explicit Hydrogens in order to see clearly that which step is the tautomerization.





My explanation about the pKa ,however, remain the same.





I will check the cationic bug what you mention.








Jozsi

Hi,


first I must continue the discussion about the enolat ion. As shown in the intensively edited (using GIMP) pictures, the situation is more complicated.





1) The first picture shows, Marvin HMO is now (after my intensive discussion in the correspondent topic) able to produce the same result independent of the given mesomeric resonance formula mrf1 or mrf2. (For mrf3 Marvin HMO doesn't work because MarvinSketch cannot recognise the three pi-centers, but this is a problem of Marvin. For a HMO calculation the enolat ion is simply a system with 3 pi centers and 4 pi electrons, and a hetero parameter for Oxygen).





2) To represent the result of this Hueckel Molecular Orbital calculation in a Valence Bond model, I have to add a third mesomeric resonance formula, which has a positive charge at C1, formula mrf 3 ( I know HMO is overestimating pi-charge-polarisations, but here the essential point is: There are more than 2 mesomeric resonance formulas to describe this ion).





3) So we have one anion represented by several mesomeric resonance formulas.





4) This anion can, as mentioned above, of course be protonated at 2 places. Protonation at C2 produces the aldehyde, protonation at C1 produces the enol.





5) So we have 2 base sites and the Marvin bpKa calculation should produce the same result for both mesomeric resonance formulas. Such as the result with bpKa1 and bpKa2 in the picture, corresponding to the 2 acid/base equivilbriums.





Regards, Hans-Ulrich

Hi, here come the cationic systems mentioned above.





1) Protonated formaldeyde, a very strong acid, gives different results using important mesomeric resonance formulas.





2) Protonated acroleine, having 3 important mesomeric resonance formulas. Here the two results to the right are different, for the mrf left there was no result. Calculating it seperately ended with the result shown left.





The handling of those ions is not correct.





Regards, Hans-Ulrich

Hi, the situation gets worse.





I tried to calculate the pKa values of an amide. This is the essential bonding group of peptides, the so called "peptide bond". As a simple model I used methylamino-acetamide.





The acid catalysed hydrolysis of those peptides begins with a protonation of the most basic site of an amide, the Oxygen atom.


See f.e. http://www.biochem.umd.edu/biochem/kahn/bchm463/pephyd.html





One model to explain the protonation at the Oxygen atom is to draw the mesomeric resonance formula mrf 2, see the second picture below.





The pKa calulations for mrf 1 show no pKa value at the Oxygen position, independent which method micro-macro or static-dynamic is used.


The N-site has a very low base pKa value.





The pKa calculations for mrf 2 show values at the Oxygen.


For the static method there is a red value 9.6 at the Oxygen, red ?


For the dynamic method there is a blue value 9.6 at the Oxygen.


But only for the method macro - dynamic the Oxygen site has the largest blue base pKa value.





What's wrong?





Regards, Hans-Ulrich

Hi,





We are working on the solution of these problem.





Jozsi

Hi, my two cents' worth on these posts.





First, pK_b is not defined as the pK_a of the conjugate acid. Instead, it is defined as something like 14 minus the pK_a of the conjugate acid. It's an unfortunate definition, because it results in two different scales for what is exactly the same property (like using both delta and tau for ¹H NMR chemical shifts), but we're stuck with it. Also unfortunately, there is no widely accepted abbreviation for "pK_a of the conjugate acid", even though we need one to substitute for "pK_b".





Second, Hans is absolutely right that different resonance structures should give the same results when their atoms' pK_as are calculated. In ACE, we developed a workaround wherein we generate the most important resonance structures of a given compound and recalculate the pK_as, taking the smallest value for an atom as the best one. We generate the resonance structures ourselves, rather than using the resonance structure plugin.

Hi,


to get a common background for the discussion in this topic here some basic sentences:





1) (Broensted)-Acids can be neutral, kationic or anionic, f.e. HCl, NH4+ or HCO3-


and also (Broensted)-Bases can be neutral, kationic or anionic, f.e. NH3, H2N-NH3+ or ClO4-


(The examples are from Roempp, Chemie-Lexikon, 1992, page 3959).





2) The definitions of pKa and pKb are totally equivalent, see the attached copy


(coming from our basic chemistry lectures).





3) There are some approximations, f.e. using solute-concentrations instead of solute-activities.





4) The approximation is also limited to diluted solutions in water.


(Of course there are also implementations for other solvents, f.e. DMSO,


but the Marvin software is obviously designed for water solutions.)





5) The following table shows some experimental examples:





pKa Acid / Base pKb


----------------------------------


4.7 CH3COOH / CH3COO- 9.3


7.2 H2PO4- / HPO4 2- 6.8


9.3 NH4+ / NH3 4.7





It is nice to memorize the following:


The important carboxylic acid CH3COOH has pKa = 4.7 and the base NH3 has pKb = 4.7





6) The usable range of these pK-values is limited.


Acids having pKa-values much lower than -1.7 react totally with water to build H3O+ and the corresponding base.


Bases having pKb-values much lower than -1.7 react totally with water to build OH- and the corresponding acid.





7) Deleted, Sun Jan 04, 2009.





I agree, the pKb value is normally not used,


and most often the pKa value of the corresponding/conjugated acid is tabulated,


and so the Marvin software must have clear notations and descriptions,


f.e. the red-blue notation.





I am open to changes here, nobody is without failures.





There is a list of problems and failures in my screenshot folder


and the sentences here are intended to give a background to post these here.





To say it once more: My intention is to get a good software suitable for teaching chemistry!





Regards, Hans-Ulrich

HUWagner wrote:

2) The definitions of pKa and pKb are totally equivalent, see the attached copy (coming from our basic chemistry lectures).

We're having an agreement, not a disagreement. The definitions of pK_a and pK_b are arithmetically related, but they are not the same values. In fact, no one uses pK_b anymore, because what's the point of learning two different values for the same property? (Like tau and delta for ¹H NMR shifts.)





So I think it is better merely to display the pK_a of the conjugate acid. When doing so, however, it is important not to use the term pK_b. Unfortunately, I think Marvin makes this very error right now. Certainly, in its chemical terms language, it uses "pKb" to indicate the pK_a of the conjugate acid.

Hi, OK, I agree.


And there is an idea for an addition to the pK notation:





pK_ca of a base is defined as the pK of the conjugated acid of the base (or the basic position in a molecule/ion).


And:


pK_a is shown in red and pK_ca is shown in blue.





"ca" is the abbreviation for "conjugated acid" (The notation "ac" could be missunderstood as only "acid").





This definition would replace "basic pKa" used in Marvin, and a special term for "acidic pKa" would be unneeded.


(Both terms are used in Marvin's User's Guide).





And the color assignment should not be manipulated by "Acid/base prefix - static - dynamic".





And this change should be accompanied by new values for the default limits:


Minimal pK_ca = - 2 and


Maximal pK_a = + 16.


This is inside the "water box", http://www.chem.wisc.edu/areas/reich/pkatable/ka-water.gif





Regards Hans-Ulrich

bobgr wrote:

So I think it is better merely to display the pKa of the conjugate acid. When doing so, however, it is important not to use the term pKb. Unfortunately, I think Marvin makes this very error right now. Certainly, in its chemical terms language, it uses "pKb" to indicate the pKa of the conjugate acid.

Thanks for all your comments, but I must make a correction here: there is no "pKb" function in Chemical Terms, it is "bpKa".





Zsolt

Hi Zsolt,

Quote:

there is no "pKb" function in Chemical Terms, it is "bpKa".

Yes, pKb came from me in my earlier definitions.





Quoting these Chemical Terms I have two questions:

Quote:

In case of "pka"result type the returned pKa values are acidic or basic (mixed!), depending on the acidic or basic character of the given atom. Acidic pKa is returned for an atom, if acidicpKa() ≤ 14.8-basicpKa(), otherwise basic pKa is returned. Specifying "acidic" or "basic" result type is required to get the acidic or basic pKa values only (also acidicpKa or basicpKa functions can be used alternatively).

1) The acidic pKa = apKa is the same as the "normal" pKa ?


2) The basic pKa = bpKa is the pKa of the conjugated/corresponding acid of the base?





Regards, Hans-Ulrich

HUWagner wrote:

Quoting these Chemical Terms I have two questions: Quote: In case of "pka"result type the returned pKa values are acidic or basic (mixed!), depending on the acidic or basic character of the given atom. Acidic pKa is returned for an atom, if acidicpKa() ≤ 14.8-basicpKa(), otherwise basic pKa is returned. Specifying "acidic" or "basic" result type is required to get the acidic or basic pKa values only (also acidicpKa or basicpKa functions can be used alternatively). 1) The acidic pKa = apKa is the same as the "normal" pKa ?

No. Here is an example, I hope it will make it clear:

Code:

$ evaluate -e "pKa()" "CC(N)C(O)=O" ;;9.48;;2.47; $ evaluate -e "apKa()" "CC(N)C(O)=O" ;;;;2.47; $ evaluate -e "bpKa()" "CC(N)C(O)=O" ;;9.48;;;

Quote:

2) The basic pKa = bpKa is the pKa of the conjugated/corresponding acid of the base?

Yes.





Zsolt

Hi Zsolt,


with "normal" pKa I meant the definition of pKa given in an earlier post of this topic.





Your interpretation


$ evaluate -e "pKa()" "CC(N)C(O)=O"


;;9.48;;2.47;


means: The Marvin function pKa() is not only the calculation of the pKa of the submitted compound,


it is also the calculation of the pKa of the conjugated acid of the submitted compound.


This is very confusing.





A function pKa() with the same name as the defined notation pKa cannot use other definitions.





(I am still analysing the red/blue scheme and have now the ppt-presentation printed on paper. There will be more questions.)





Regards, Hans-Ulrich

We need a translator.





Chemical Terms "pKa" means, "pK_a's of acids (shown in red) and pK_a's of the conjugate acids of bases (shown in blue)."





Chemical Terms "apKa" means, "pK_a's of acids (shown in red)."





Chemical Terms "bpKa" means, "pK_a's of the conjugate acids of bases (shown in blue)."





In the GUI, the red and blue coloration makes the results not confusing. But in the command line version, where coloration is not given, Hans is right, the results are very confusing. They would not be as confusing if the values were returned with a (ca) or (a) following them.

Code:

$ evaluate -e "pKa()" "CC(N)C(O)=O" ;;9.48 (ca);;2.47 (a);

Yes, we need translation.


Translation between the "Marvin Chemical Terms Language" http://www.chemaxon.com/marvin/help/chemicalterms/ChemicalTerms.html


and the "normal" chemical language used in literature and lectures.





Until now I didn't find the IUPAC definition of "pKa" but I think, the definition given in my earlier posts in this topic is the commonly used version,


and pKca is not the same as pKa.





For me the translation is: The Marvin Chemical Terms function pKa() gives in "normal" chemical language both pKa and pKca results, but the naming of the function doesn't say this. Only the language definition in the table mentioned above declares it. That's a problem for users who are learning chemistry.





And before discussing the red/blue coloration one question:


Is there a command line equivalent to the GUI options "Acid/base prefix static/dynamic" ?





Regards, Hans-Ulrich

Hi, please, one question more:





Is it right simply to replace in the presentation redBlue.ppt


"default" by "static" and "non-default" by "dynamic" ?


As defined on page 4.





Regards, Hans-Ulrich

Hi,

Quote:

Is it right simply to replace in the presentation redBlue.ppt "default" by "static" and "non-default" by "dynamic" ?

Yes, it is right.








Jozsi

Hi Jozsi,


now I have edited the redBlue.ppt presentation and prepared a documenation to show the definition of the option dynamic and the red/blue notation.


Please see the image redBlue1S.png.





I have changed the direction of the reaction-equation 3). Now it has the same direction as the equations 1) and 2) and shows the same pKa definitions.





The red/blue notation is now exactly defined as red=deprotonation and blue=protonation of a molecule/site-in-a-molecule.





This is a real feature of the dynamic model ! Super !





Please change the default acid/base prefix to dynamic.





I am prepairing a documentation for this red/blue notation with another example.


The NH3-example is not so good, because it's "33.62" value is outside the "waterbox"


and cannot be demonstrated with another feature of MarvinSketch: the showing of the microspecies distribution.


It will be an example inside the "waterbox".





Regards, Hans-Ulrich

Hi Hans,

 

I tried to calculate the pKa values of an amide. This is the essential bonding group of peptides, the so called "peptide bond". As a simple model I used methylamino-acetamide.

The acid catalysed hydrolysis of those peptides begins with a protonation of the most basic site of an amide, the Oxygen atom.

 

I changed the basic atom specification for amides.  This modification will appear in the outgoing release at the next week.

Jozsi

Hi Jozsi,

thank you for your answer. So I'm eagerly awaiting the next release.

Regards, Hans