ACD/pK_a DB

Technical Information, Page 2

• Varieties of pK_a 
• Microscopic vs. Macroscopic pK_a Constants 
• How Does ACD/pK_a DB Predict pK_a Values?  
• Calculations 

ACD/pK_a is very clear about which type of pK_a is being calculated. There are two general categories of pK_a requested:

• For specific input of a molecular form - to designate ionization occurring at a particular ionization center.
• For the general form of the molecule - to simulate the stages of actual ionization in solution.

The pK_a of each particular ionization center in the drawn scheme is called the microconstant (K_A, K_B, K_C & K_D):

The pK_a values which are actually measured in aqueous solution, however, are called the macroscopic, or apparent, pK_a constants. The macroscopic constants are related to the above mentioned microconstants by the following equation:

.

We call such macroscopic constants the apparent exact pK_a values since they are obtained through the exact theoretical equations.

ACD/pK_a calculates macroconstants using the approximated theoretical equations which lead to the apparent approximate pK_a for very complex molecules where the calculation of exact pK_a is impossible.

It is very important to make sure that your pK_a software can handle calculations of both apparent and microconstants and clearly specifies which is which. For example, the molecule glycine, which is often expressed in chemical form as H₂N—CH₂—COOH in reality exists in solution at neutral pH in zwitterionic form, H₃N⁺--CH₂—COO^-. If you sketch in the neutral form, your pK_a software should be smart enough to handle this common problem of translating from the formula to the actual presence in solution.

In certain cases, however, you might want to look at a "what if?" case and thus you might want to calculate the pK_a for a "forced" equilibrium of the type:

H₂N—CH₂--COOH H₂N—CH₂—COO^- + H⁺

For this case, it is helpful to have software which allows you to request the "microconstant" pK_a.