On the pH memory of lyophilized compounds containing protein functional groups

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Abstract
Lyophilized proteins exhibit “pH memory,” i.e., their behavior in the solid form corresponds to the pH of the aqueous solution from which they were freeze dried. Herein, we directly tested whether the ionization state is “remembered” by model organic compounds containing various protein functional groups (amino, carboxyl, and phenolic). The fraction of ionized species was quantitated from the infrared spectra of both the aqueous and lyophilized states. The pKa values in the aqueous and lyophilized forms for each compound were found to be quite similar, within 0.3 units from each other. © 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 53: 345–348, 1997.