Acid/base chemistry: Applications of hard-soft acid-base theory

The HSAB (Hard Soft Acid Base) theory categorizes chemical species as acids or bases and as “hard”, “soft”, or “borderline”. It explains that soft acids or bases tend to be large and very polarizable, while hard acids or bases are small and non-polarizable. Since these categories are not absolute, there are species that are considered borderline, which lie in between hard and soft. Generally, we could characterize hard acids and bases as having:

A hard acid or base may have some or all of these characteristics, but the hard-soft distinction is most directly linked to polarizability. Polarizability is the relative tendency of the electron cloud to be distorted from its normal shape.

Table 1. Table of representative hard, borderline, and soft acids and bases

The theory elaborates that hard acids prefer to bond with hard bases, and the resulting adduct tend to have more ionic character in its bonding. Correspondingly, soft acids prefer to bond with soft bases, and their adducts are more covalent in nature.

The concept has been used in chemistry to explain the stability of various compounds, pathways, or reaction mechanisms. In transition metal chemistry, it offers a qualitative approach to understanding metal-ligand interactions in complexation reactions. Here are the ${\text{K}}_{eq}$‍ values for two such ligand exchange reactions:

${\text{[CH}}_3{\text{Hg(H}}_2{\text{O)]}}^{+}\text{ + HF}$‍ ⇋ ${\text{CH}}_3{\text{HgF + H}}_3{\text{O}}^{+}{\text{K}}_{eq}\text{ = }4.5\times {10}^{-2}$‍

${\text{[CH}}_3{\text{Hg(H}}_2{\text{O)]}}^{+}\text{ + HBr}$‍ ⇋ ${\text{CH}}_3{\text{HgBr + H}}_3{\text{O}}^{+}{\text{K}}_{eq}\text{ = }4.2\times {10}^{15}$‍

In toxicology, the HSAB theory has recently proved useful in predicting toxicant-target interactions, whereby most electrophiles are the toxicants and most nucleophiles are biological macromolecules, in particular, thiols and thiolates in cysteine and amines in lysine. Cytotoxicity occurs when toxicants like acrolein and vinyl chloride form adducts with biomacromolecules of similar hardness or softness, thus impair cellular function. One of the compounds under investigation is curcumin, a phenol found in turmeric, and its structure is below:

Figure 1. Structure of Curcumin

Source: Adapted from a paper by R. LoPachin, et al. Copyright 2011 by American Chemical Society.