Induced CD of iron(ii) clathrochelates: sensing of the structural and conformational alterations of serum albumins.

Abstract

An ability of inherently achiral macrobicyclic metal complexes iron(ii) clathrochelates to acquire an induced CD (ICD) output in the visible spectral range upon interaction with bovine serum albumin (BSA) was recently discovered. In the present work, the CD-reporting properties of iron(ii) clathrochelates to proteins and the thermodynamic parameters of their binding to albumins are evaluated. It is shown that iron(ii) clathrochelates functionalized by six ribbed carboxyphenylsulfide groups are able to discriminate between serum albumins of relative structure (here human and bovine albumins) by giving distinct ICD spectra. Besides, by the variation of the shape and intensity of CD bands, these cage metal complexes reflect the pH-triggered alterations of the tertiary structure of albumins. The constitutional isomerism (ortho-, meta- or para-isomers) of terminal carboxyphenylsulfide groups of iron(ii) clathrochelates strongly affects both the character of their ICD output upon binding with proteins and the parameters of the formed guest-host associates. Using isothermal titration calorimetry, it was determined that cage metal complexes bearing meta- and ortho-isomers of carboxyphenylsulfide groups possess higher association constants (Ka ∼ 2 × 104 M-1) and clathrochelate-to-BSA binding ratios (n = 2) than the para-isomer (Ka ∼ 5 × 103 M-1, n = 1). The iron(ii) clathrochelates are suggested to be potential molecular three-dimensional scaffolds for the design of CD-sensitive reporters able to recognize specific elements of protein surfaces.