Ferrocene–β‐Cyclodextrin Conjugates: Synthesis, Supramolecular Behavior, and Use as Electrochemical Sensors

Abstract

Ferrocene with a beta-cyclodextrin unit bound to one or both cyclopentadienyl rings through the secondary face were conveniently synthesized by regiospecific copper(I)-catalyzed cycloaddition of 2-O-propargyl-beta-cyclodextrin to azidomethyl or bis(azidomethyl)ferrocene. The supramolecular behavior of the synthesized conjugates in both the absence and presence of bile salts (sodium cholate, deoxycholate, and chenodeoxycholate) was studied by using electrochemical methods (cyclic and differential pulse voltammetry), isothermal titration calorimetry, and NMR spectroscopy (PGSE, CPMG, and 2D-ROESY). These techniques allowed the determination of stability constants, mode of inclusion, and diffusion coefficients for complexes formed with the neutral and, in some cases, the oxidized states of the ferrocenyl conjugates. It was found that the ferrocenyl conjugate with one beta-cyclodextrin unit forms a redox-controllable head-to-head homodimer in aqueous solution. The ferrocene-bis(beta-cyclodextrin) conjugate is present in two distinguishable forms in aqueous solution, each one having a different half-wave oxidation potential for the oxidation of the ferrocene. By contrast, only one distinguishable form for the oxidized state of the ferrocene-beta-cyclodextrin conjugate is detectable. The redox-sensing abilities of the synthesized conjugates towards the bile salts were evaluated based on the observed guest-induced changes in both the half-wave potential and the current peak intensity of the electroactive moiety.

Synthesis, physical and antimicrobial studies of ferrocenyl-N-(pyridinylmethylene)anilines and ferrocenyl-N-(pyridinylmethyl)anilines

“…7,8 The ferrocenyl unit is also known to modify the shapes of molecules as well as the physical properties such as colour, polarizability and magnetism. 9 Generally, studies on ferrocene revolve around generation of compounds that are used in materials science, 10 electrochemistry 11,12 catalysis, [13][14][15] medicinal applications [16][17][18][19][20][21][22][23][24] and nonlinear optics 25,26 amongst others. Ferrocene derivatives containing organic fragments bearing one or more heteroatoms such as sulphur, 27 nitrogen, 28 oxygen, 29 and phosphorous 30 have gained prominence.…”

Thermodynamics of Resulting Complexes Between Cyclodextrins and Bile Salts

“…A study of 13 C chemical shifts as a function of concentration at different pH values has been performed by Tato et al, which shows a different behavior of complexation for CA and DCA with 5 resulting in 1:1 and 1:2 inclusion complexes [22]. However, the complexation phenomena do not depend on the pH of the solution.…”

“…However, the complexation phenomena do not depend on the pH of the solution. 13 C NMR chemical shifts of the host and guest molecules change on passing from the free to the complexed state. The side chains in 5 at position C-6 have a significant effect on the complexation process with the bile salts.…”

“…Among the numerous guests researched, bile salts attracted much more attention because they are one kind of important surfactant-like biological amphipathic compounds possessing a steroid skeleton, which have distinctive detergent properties and play an important role in the metabolism and excretion of cholesterol in mammals [6]. For example: the thermodynamics and structure of inclusion compounds of glyco-and tauro-conjugated bile salts with CDs and their derivatives have been studied by Holm et al during the last years [7][8][9][10][11]; the interactions of different kinds of bile salts with -CD dimers linked through their secondary faces have been investigated by Reinhoudt and Vargas-Berenguel et al [12][13][14]. It has been demonstrated that the formation of inclusion complexes between CDs and guest molecules is cooperatively governed by several weak forces, such as van der Waals interactions, hydrophobic interactions, hydrogen bonding, electrostatic interactions, and every weak force does its contribution to the complexation.…”

Electrochemistry of Cyclodextrin Inclusion Complexes of Pharmaceutical Compounds

“…The redox-sensing abilities of a synthesized conjugate, Ferrocene with a -cyclodextrin unit bound to one or both cyclopentadienyl rings through the secondary face, towards bile salts (sodium cholate, deoxycholate, and chenodeoxycholate) has been evaluated using electrochemical methods (cyclic and differential pulse voltammetry) [127]. These techniques allowed the determination of stability constants, mode of inclusion, and diffusion coefficients for complexes formed with the neutral and, in some cases, the oxidized states of the ferrocenyl conjugates.…”