What is the pKa and How is it determined

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Introduction and outcome: pKa and pH

pKa and pH play a crucial role in pharmaceutical analysis. Be it chromatographic analysis or titration or chemical synthesis everywhere both act as important deciding parameters. That’s why I decided to share my skill-based knowledge on these topics. In this article, you will learn pH, pKa, the relationship between pH and pKa, the difference between pH and pKa, applications, the determination of pKa and pH, case studies and frequently asked questions.

pH definition

pH = -log₁₀[H⁺]—–(Equation-1)

pH is defined as negative logarithm of the hydrogen ions concentration.

It measures how acidic or alkaline a compound or solution is. pH is measured on a scale of 0 to 14. On this scale, a pH value of 7 is neutral, meaning it is neither acidic nor alkaline. A pH value less than 7 means it is more acidic, and a pH value greater than 7 means it is more alkaline. Equation-1 is very helpful in calculating pH of a given solution.

Case study-1

What will be pH of 0.0001M Hydrochloric solution?

Here concentration of H⁺ or [H⁺] is 0.0001

Therefore pH = -log10[0.00001] or pH = log10[10^-4] or pH = – x (-4)log[10] or pH = 4×1 = 4

Effect of temperature on pH

The following are the relationship between pH and temperature (T)

pH ∝ 1/T

pKa definition

pKa = -log₁₀Ka—–(Equation-2)

pKa is the negative base 10 logarithm of Ka (acid dissociation constant) of a solution. pKa is the characteristic of a particular compound and it tells about how readily the compound gives up a proton (H⁺)

From Equation-2 it is clear that:

• When Ka is large pKa small and acid is strong
• When Ka is small pKa large and acid is weak

Typical compounds and their pKa

Case study-2

Calculate the pKa value of acetic acid. Ka of acetic acid is 1.8 x 10^-5

Here Ka of acetic acid is 1.8 x 10^-5. Hence from equation-2 pKa of acetic acid will be

pKa = -log₁₀(1.8 x 10^-5 ) or pKa =-{log₁₀(1.8) +-log₁₀(10^-5 )} or pKa = -{0.255 – 5) =4.775

Difference between pKa and pH

Applications of pH and pKa

The following are some important applications of pH and pKa;

• Both pH and pKa are very helpful in HPLC method development; Such as for separation/development of nonpolar, acidic and basic compounds
• pKa defines whether a molecule is a strong acid or weak acidic
• pKa is very helpful in drug development. For example, pKa influences the solubility, oral absorption, distribution, and pharmacokinetics of a drug
• pKa helps in determining the ionisation state of a drug at different physiological pH levels
• pH defines acidic or basic nature of a molecule
• pH is very helpful in assay method development by titration method (e.g. acid-base titration)
• pH play an important role in human digestive system. When we eat food
• pH of the soil play an important role in growth of crops and other plants. Ideal pH of soil should be 6.5 to 7.3 for growth of the crops or plants.
• When pH of mouth becomes lower than 5.5 our teeth start decaying.

pKa determination procedure

The following methods are widely used to determine the pKa of a molecule:

• Titration method
• Ultraviolet spectroscopy method and
• High-pressure liquid chromatography (HPLC) method

Titration method

In this method the molecule is dissolved in water or a mixture of water and suitable solvent/solvents. The solution is titrated against 0.1N Sodium hydroxide volumetric solution (or any other lower concentration) and pH is measured beyond the endpoint.

pKa = pH at half of the endpoint volume

Ultraviolet spectroscopy method

Procedure:

• The molecule stock solution is prepared in the suitable solvent
• 10 mcg/ml solution is prepared by from stock solution by diluting with a series of buffer solutions (buffer of pH between 2 to 8)
• UV absorption of each solution is taken at two wavelengths using ultraviolet spectrophotometer
• The pH at which the molecule gives the same absorbance is the pKa of the molecule

pH determination procedure

Relation between pKa and pH or Henderson equation

The following are the relationship between pH and pKa:

pH = pKa + Log10 ([Salt]/[Acid])—-(Equation-3)

or

pH = pKa + Log10 ([A^–]/[HA])

Where [A^–] is molar concentration of conjugate base and HA is the molar concentration of acid.

Equation-3 is also called Henderson equation and it is also used to calculate pKa of the a molecule.

Note: When [Acid ] or [Unionised] = [salt] or [Ionised] then pH = pKa (this is the titration method of pKa determination)

Conclusion

Both pKa and pH play unique roles in ensuring product quality, safety, and effectiveness in various industries. Be it pharmaceutical industry or food industry or water treatment plant or agriculture or textile or automotive industry, pKa and pH optimization helps in getting the desired product. I hope this article has helped you understand pKa and pH and their importunate. Now you can independently and effectively apply during pharmaceutical analysis. You may also want to check out other articles on my blog, such as SOP for calibration of pH meter and Karl Fischer-titration for water determination.

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FAQs

What is the relationship between pH and pKa?

pH = pKa + Log10 ([Salt]/[Acid])

What is pKa value to acidity?

pKa is one of the method of determining acid strength. When pKa is small and acid is strong and when pKa is large and acid is weak.

Does pKa and pKb equal 14?

Yes. pKa + pKb = 14

Does a higher pKa mean a lower pH?

No. pH ∝ pKa (pH is directly proportional to pKa)

How to determine pKa from pH?

The equation pH = pKa + Log10 ([Salt]/[Acid] is used to determine pKa from pH:

How do you convert pKa to Ka?

Equation pKa = -log₁₀Ka can be used to convert pKa to Ka.

What is the pKa of NaOH?

NaOH (Sodium hydroxide) is a strong base and its pKa is 13.8

Why is benzoic acid (pKa=4.20) more acidic than acetic acid (pKa=4.76)?

After releasing the proton Benzoate anion of Benzoic acid is stabilised by resonance. Whereas acetate anion of acetic acid is not. That is why benzoic acid (pKa=4.20) is more acidic than acetic acid (pKa=4.76).

How is the pKa for a titration curve calculated?

pH = pKa + Log10 ([Salt]/[Acid]

When is the pH equal to the pKa value?

The equation pH = pKa + Log10 ([Salt]/[Acid]), shows the relationship between pH and pKa.

When the concentration of [Acid ] = [salt] then pH = pKa.

What is the relationship between acidity and pKa?

The equation pH = pKa + Log10 ([Salt]/[Acid]), shows the relationship between acidity (pH) and pKa.

What does a high pKa indicate?

High pKa indicates weak acid.

What determines the pKa of an acid?

When pKa is small and acid is strong and when pKa is large and acid is weak.

Which is a stronger acid, one with a pka of 5.2 or one with a pka of 5.8?

one with a pka of 5.2

How do you find pKa from Ka?

Using equation pKa = -log₁₀Ka, one can find pKa from Ka

Does pKa change with pH?

Yes.

Is pKa the same as pH?

Yes. pKa may become equal pH

How does pKa relate to pH?

The equation pH = pKa + Log10 ([Salt]/[Acid]), shows the relationship between pH and pKa.

Can the pH of a pure liquid organic molecule be measured?

pH of a pure liquid organic molecule can not be measured. It must be dissolved in water or extracted in water and then pH of aqueous solution should be measured.

How to calculate pH?

The equation pH = -log10[H⁺], should be used to calculate the pH.

What is pH full form pH?

The full form of pH is potential of Hydrogen

What is the pH formula and definition?

pH = -log10[H+]. pH is defined as negative logarithm of the hydrogen ions concentration

Does pH depend on temperature?

Yes. pH ∝ (1/Temperature)

References

• https://groups.chem.ubc.ca/courseware/pH/section19/index.html

Abbreviations

• pH: potential of Hydrogen
• Ka: acid dissociation constant
• HA: Acid