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 Å(3)) in ten synthetic steps. With the assistance of (1)H 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 Å(3)) and the larger 2 for various solvents as guests were quantified by (1)H NMR spectroscopy in CD2Cl2 (61 Å(3)), CDCl3 (75 Å(3)), CFCl3 (81 Å(3)) and CCl4 (89 Å(3)); the apparent guest binding equilibria Ka were found to be inversely proportional to the affinity of bulk solvents KS for populating each host. The rate of the P/M racemization (krac, 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/M vs. 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) RM1-2 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 RM1-2, whereas, a greater packing, represented when PC > 0.3, enforces the geared RM3 mechanistic alternative.

On the Nature of the Transition State Characterizing Gated Molecular Encapsulations

“…It is indeed difficult to repudiate this particular mechanistic scenario, although we have not observed any intermediate either spectroscopically or kinetically (the saturation kinetics) [18] to suggest the two-step process [23]. In addition, en earlier study [26] indicated that for a guest populating the basket's inner space to a greater extent (PC > 0.3, Table 1) the basket's racemization necessitates simultaneous opening of all three gates. Free E n ergy R .…”

“…In fact, there exists a linear free energy relationship (LFER) with log k out being proportional to the volume of solvent molecules (R 2 = 0.97, Figure 3A). [2] ) [26]. The measured affinity constants (K a , Table 1) suggest for the stability of [1-solvent] complexes to be in the order: Figure 3D).…”

“…H NMR spectroscopic measurements (via signal integration) at 300.1 K, while k in was calculated as k in = K a k out . Solubility (S) of basket 1, in 3-6, was determined with the assistance of 19 F NMR spectroscopy at 300.1 K. Packing coefficients (PC) were calculated as PC (%) = V guest /V host's inner space [26]. Evidently, more favorable decomplexations of [1][2] (smaller log K a , Figure 3B) are, in solvents 3-6, occurring at a faster rate (bigger log k out ).…”

“…Consequently, the stability of [1][2] complex is, in aromatic solvents 3-6, comparable and therefore shown in Figure 3D as one state. At last, the experimental order of stability of [1-solvent] complexes tracks an increased population of the inner space of basket 1 (approximated PCs are given in Table 1) [26]. H NMR spectroscopic measurements (via signal integration) at 300.1 K, while k in was calculated as k in = K a k out .…”

“…Three aminopyridine rings [24], containing hydrogen-bonding donor and acceptor sites, are attached to the rim of the platform to, via CH 2 "hinges", act as gates that, by controlling the portal size, regulate the in/out encapsulation of small haloalkanes (V ~ 88-120 Å 3 ) [25]. The formation of basket/guest complex was, in solvophobic CD 2 Cl 2 solvent (V = 61 Å 3 ) [26], found to be first-while the dissociation is zeroth-order in guests ( Figure 1) [20]. In essence, the basket undergoes a rapid thermal racemization (∆G ‡ rac < 11 kcal/mol) to, occasionally, permit the entrance/departure of guest molecules [27].…”