A journey from calix[4]arene to calix[6] and calix[8]arene reveals more than a matter of size. Receptor concentration affects the stability and stoichiometric nature of the complexes

Abstract

The formation of inclusion complexes between lucigenin (N,N'-dimethyl-9,9'-biacridinium dinitrate) and p-sulfonatocalix[n]arenes (SCn; n = 6, 8) was investigated by fluorescence and NMR spectroscopy. Both SC6 and SC8 were found to form 1 : 1 and 1 : 2 host-guest complexes with lucigenin showing up to 10 M binding affinities. Strong quenching of the lucigenin fluorescence upon complexation was observed. Fluorescence regeneration after competitive binding with other potential guests present in solution was used as an indicator displacement assay to characterize the binding mechanism and affinity of alkaline metal ions (Li, Na, K and Cs) with SC6 and SC8. The results demonstrate the formation of 1 : 1 and 1 : 2 calixarene : metal complexes with association constants on the order of 10 M and heteroternary calixarene : lucigenin : metal complexes that predominate at metal cation concentrations above the millimolar range. Owing to the ubiquitous presence of metal cations in SCn solutions as counterions (typically Na), the detailed description of the complexation of these species is crucial to understand and quantify the host-guest binding properties of these receptors. This work demonstrates that both the thermodynamic stability and the stoichiometric nature of the complexes is dependent on the metal ion concentration and, consequently, on the calixarene concentration.

Sulfonatocalixarene Counterion Exchange Binding Model in Action: Metal‐Ion Catalysis Through Host‐Guest Complexation

“…In the same manner, the stability of the 1 : 2 SCn : Ni 2 + complex shows negative cooperativity due to partial charge neutralization during the formation of the binary species. [38] As can be observed from Scheme 4, the number of species that can be formed for SC6 and SC8 increase substantially with respect to SC4. This complex dynamic multistate system arises from the fact that these hosts can form 1 : 1, 1 : 2 and heteroternary complexes with the cations present in solution.…”

“…However, it must be stressed that for the concentrations of SCn used here, SC6 and SC8 exist in solution as 1 : 1 and 1 : 2 sodium complexes and that different stoichiometric complexes containing 1, SCn and Na + are likely to occur. [28,[36][37][38][39] Therefore k must be considered as an apparent rate constant that results from the sum of the rate constants of the different complexes averaged by their relative mole fraction.…”

“…Before analyzing the kinetic data presented in Figure 3, the binding constants for Ni 2 + towards SC6 and SC8 were determined using the lucigenin displacement assay protocol previously stablished for other metal cations (see the Supporting Information). [38] This allowed the determination of the following binding constants K Ni = 1.6x10 5 M À 1 , K 2Ni = 2.4 × 10 3 M À 1 for SC6 and K Ni = 1.5 × 10 6 M À 1 , K 2Ni = 8.5 × 10 3 M À 1 for SC8. The values are in agreement with an increase in the stability of the complexes as the charge of the host and guest increase, as expected for the formation of non-covalent species dominated by attractive coulombic interactions.…”

“…This complex dynamic multistate system arises from the fact that these hosts can form 1 : 1, 1 : 2 and heteroternary complexes with the cations present in solution. [38] Then, the calixarene-metal complexes may bind 1 to form the respective ternary and quaternary complexes. In order to simplify the analysis of the kinetic data we neglected the potential formation of 1 : 2 host:guest complexes between SC6/ 8 and 1.…”

“…K 1 can be neglected as it does not contribute significantly to k obs because the concentration of free SC6 or SC8 is very small under the experimental conditions, i. e., their complexes with metal cations predominate. [38] However, due to the large number of correlated parameters the binding and kinetics constants cannot be all accurately determined from the fitting. Nevertheless, some parameters can be estimated and the ones that included errors can be determined assuming the described approximations.…”