Skip to main content

pKa, Zinc- and Serum Albumin-Binding of Curcumin and Two Novel Biologically- Active Chemically-Modified Curcumins

Buy Article:

$55.00 plus tax (Refund Policy)

The pH equilibria and the zinc ion and bovine serum albumin (BSA) binding behavior of curcumin and two chemically modified curcumins (CMCs), namely 4-methoxycarbonylcurcumin (CMC 2.5) and 4-phenylaminocarbonyl bis-demethoxy curcumin (CMC 2.24), were studied, in order to understand the basis of their differential effects on the zinc-enzyme matrix metalloproteinases (MMPs) as well as the effect of charge state on their behavior in vivo. Moreover, all three compounds transform rapidly in the pH range 5-10, CMC 2.5 largely in one step, and CMC 2.24 and curcumin first in a rapid process to an intermediate form that still displays an enolic and two phenolic hydrogen-ion equilibria, and then more slowly to forms absorbing primarily in the lower UV and lacking the strong absorbance in the visible characteristic of the enol-centered chromophore. The binding of these compounds in one of the hydrophobic pockets of the major transport protein, serum albumin, was therefore studied. CMC 2.24 binds more strongly to BSA than curcumin, with a dissociation constant of 0.56±0.08 μM compared to 1.32±0.17 μM. Binding to BSA shifts the decomposition half-lives from tens of seconds to tens of hours. The zero-time acid dissociation constants (pKa) for species H3D, H2D-, and HD2- are 8.41, 9.94 and 11.2; 6.98, 8.40 and 9.8; and 6.50 and 8.82 ; for curcumin, CMC 2.24, and CMC 2.5 respectively (there is no distinguishable pKa3 for CMC 2.5). Zn2+ binds most strongly to CMC 2.24 compared to CMC 2.5 and curcumin, with dissociation constants of 0.77±0.02, 1.88±0.07, and 1.39±0.09 mM. The increased acidity and Zn2+ and BSA affinities of CMC 2.24 correlate with its greater biological activity.
No References
No Citations
No Supplementary Data
No Article Media
No Metrics

Keywords: Forster energy transfer; Matrix metalloproteinase; UV-visible absorbance and equilibria; bovine serum albumin binding; curcumin; fluorescence quenching; pKa; time-dependence; zinc-binding

Document Type: Research Article

Publication date: 2012-09-01

More about this publication?
  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
  • Access Key
  • Free content
  • Partial Free content
  • New content
  • Open access content
  • Partial Open access content
  • Subscribed content
  • Partial Subscribed content
  • Free trial content
Cookie Policy
Cookie Policy
Ingenta Connect website makes use of cookies so as to keep track of data that you have filled in. I am Happy with this Find out more