On the role of guests in enforcing the mechanism of action of gated baskets

Abstract

We designed and prepared a spacious and gated basket of type 2 (V = 318 ų) in ten synthetic steps. With the assistance of ¹H NMR spectroscopy, we found that the pyridine gates at the rim of 2 form a seam of N–H⋯N hydrogen bonds, thereby adopting right- (P) and left-handed (M) helical arrangements. The recognition characteristics of the smaller basket 1 (V = 226 ų) and the larger 2 for various solvents as guests were quantified by ¹H NMR spectroscopy in CD₂Cl₂ (61 ų), CDCl₃ (75 ų), CFCl₃ (81 ų) and CCl₄ (89 ų); the apparent guest binding equilibria K_a were found to be inversely proportional to the affinity of bulk solvents K_S for populating each host. The rate of the P/M racemization (k_rac, s⁻¹) was, for both 1 and 2, studied in all four solvents using dynamic NMR spectroscopy. From these experiments, two isokinetic relationships (ΔS^‡_P/Mvs. ΔH^‡_P/M) were identified with each one corresponding to a different mechanism of P/M racemization. A computational study (B3LYP/6-31+G**//PM6) of 1 and 2 in the gas phase indicates two competing racemization pathways: (a) RM_1–2 describes a pivoting of a single gate followed by the rotation of the remaining two gates, while (b) RM₃ depicts simultaneous (geared) rotation of all three gates. The racemization of the larger basket 2, in all four solvents (packing coefficient, PC = 0.19–0.28), conformed to one isokinetic relationship, which also coincided with the operation of the smaller basket 1 in CD₂Cl₂ (PC = 0.27). However, in CDCl₃, CFCl₃ and CCl₄ (PC = 0.33–0.39), the mode of action of 1 appears to correlate with a different isokinetic relationship. Thus, we propose that the population of the basket's inner space (PC) determines the mechanism of P/M racemization. When PC < 0.3, the mechanism of operation is RM_1–2, whereas, a greater packing, represented when PC > 0.3, enforces the geared RM₃ mechanistic alternative.