Dynamics in Host–Guest Complexes of Molecular Tweezers and Clips

Abstract

The dynamics in the host-guest complexes of the molecular tweezers 1 a,b and clips 2 a,b with 1,2,4,5-tetracyanobenzene (TCNB, 3) and tropylium tetrafluoroborate (4) as guest molecules were analyzed by temperature-dependent 1H NMR spectroscopy. The TCNB complexes of tweezers 1 a,b were found to be particularly stable (dissociation barrier: DeltaG(++)=16.8 and 15.7 kcal mol(-1), respectively), more stable than the TCNB complexes of clips 2 a,b and the tropylium complex of tweezer 1 b (dissociation barrier: DeltaG(++)=12.4, 11.2, and 12.3 kcal mol(-1), respectively). A detailed analysis of the kinetic and thermodynamic data (especially the negative entropies of activation found for complex dissociation) suggests that in the transition state of dissociation the guest molecule is still clipped between the aromatic tips of the host molecule. The 1H NMR analysis of the TCNB complexes 3@1 b and 3@2 a at low temperatures (T<-80 degrees C) showed that 3 undergoes fast rotation inside the cavity of tweezer 1 b or clip 2 a (rotational barrier: DeltaG( not equal)=11.7 and 8.3 kcal mol(-1), respectively). This rotation of a guest molecule inside the host cavity can be considered to be the dynamic equilibration of noncovalent conformers. In the case of clip complex 3@2 a the association and rotational barriers are smaller by DeltaDeltaG(++)=3-4 kcal mol(-1) than those in tweezer complexes 3@1 a,b. This can be explained by the more open topology of the trimethylene-bridged clips compared to the tetramethylene-bridged tweezers. Finally, the bromo substituents in the newly prepared clip 2 b have a substantial effect on the kinetics and thermodynamics of complex formation. Clip 2 b forms weaker complexes with (TCNB, 3) and tetracyanoquinodimethane (TCNQ, 12) and a more stable complex with 2,4,7-trinitrofluoren-9-ylidene (TNF, 13) than the parent clip 2 a. These results can be explained by a less negative electrostatic potential surface (EPS) inside the cavity and a larger van der Waals contact surface of 2 b compared to 2 a. In the case of the highly electron-deficient guest molecules TCNB and TCNQ the attractive electrostatic interaction is predominant and hence responsible for the thermodynamic complex stability, whereas in the case of TNF with its extended pi system, dispersion forces are more important for host-guest binding.

Building on Cram’s Legacy: Stimulated Gating in Hemicarcerands

“…18 Gating has also been explored in Klärner’s molecular tweezers, 19 Badjić’s molecular baskets, 20 and Cram’s “vase-kite” cavitands 21 (Figure 8). These types of hosts have been reviewed recently by Badjić and by our group.…”

Donor/Acceptor‐Substituted Chiral Molecular Clips – Synthesis and Host–Guest Complex Formation

“…The observation of only one shifted 1 H NMR guest signal for each TCNB complex and two guest signals for each KS complex is good evidence for dynamic complex structures, which means that the rotation of the guest molecule inside the clip cavity and the mutual host–guest association and dissociation are fast processes with respect to the NMR timescale. Thus, in each complex, the observed NMR signals of these protons are averaged, which is comparable to the corresponding host–guest complexes of the tetramethylene‐bridged tweezers and trimethylene‐bridged clips, for which separate signals for the guest protons were observed at very low temperature 15…”

“…Determination of the Binding Constants, K a , and the Complexation‐Induced 1 H NMR Shift of the Guest Protons, Δ δ max , by NMR Titration Experiments: The binding constants K a and the complexation‐induced 1 H NMR shifts of the guest protons Δ δ max were determined by NMR titration experiments. In each experiment the total guest concentration was kept constant and the total host concentration was varied, as described 15…”

Chronic pain 5 years after randomized comparison of laparoscopic and Lichtenstein inguinal hernia repair (Br J Surg 2010; 97: 600–608)

“…The rate constant at this temperature k c is then π Δ ν /2 0.5 . Although this correlation strictly only applies to dynamic equilibria in which the interconverting species are equally populated, are transformed into one another through first‐order reactions, and possess peaks in the NMR spectra that do not exhibit coupling, this correlation has also been shown to provide a rough estimate of reaction rates that do not fulfill all of these requirements, including binding equilibria 28. The problems associated with studying binding equilibria are: 1) only complex dissociation is usually a first‐order reaction, whereas complex formation follows a second‐order rate law and 2) temperature variation not only affects binding kinetics but also the ratio of free and complexed binding partners, namely, the thermodynamics.…”