Remember, ionic strength is calculated as one half of the sum of the concentration (C) of all (n) charged species multiplied by the charge (z) SQUARED:
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Thus, the greater the charge on each species, the more the effect on ionic strength. A typical case: adding 10mM EDTA as a putative enzyme inhibitor at pH 8.0 increases the ionic strength of the assay by a huge amount - hardly a controlled experiment - two variables have changed - ionic strength and 'inhibitor' concentration! To see how much ionic strength can affect a buffer, go to the next card...