Archive for the 'host-guest' Category

Highly efficient Buckycatchers

Capturing buckyballs involves molecular design based on non-covalent interactions. This poses interesting challenges for both the designer and the computational chemist. The curved surface of the buckyball demands a sequestering agent with a complementary curved surface, likely an aromatic curved surface to facilitate π-π stacking interactions. For the computational chemist, weak interactions, like dispersion and π-π stacking demand special attention, particularly density functionals designed to account for these interactions.

Two very intriguing new buckycatchers were recently prepared in the Sygula lab, and also examined by DFT.1 Compounds 1 and 2 make use of the scaffold developed by Klärner.2 In these two buckycatchers, the tongs are corranulenes, providing a curved aromatic surface to match the C60 and C70 surface. They differ in the length of the connector unit.

B97-D/TZVP computations of the complex of 1 and 2 with C60 were carried out. The optimized structures are shown in Figure 1. The binding energies (computed at B97-D/QZVP*//B97-D/TZVP) of these two complexes are really quite large. The binding energy for 1:C60 is 33.6 kcal mol-1, comparable to some previous Buckycatchers, but the binding energy of 2:C60 is 50.0 kcal mol-1, larger than any predicted before.



Figure 1. B97-D/TZVP optimized geometries of 1:C60and 2:C60.

Measurement of the binding energy using NMR was complicated by a competition for one or two molecules of 2 binding to buckyballs. Nonetheless, the experimental data show 2 binds to C60 and C70 more effectively than any previous host. They were also able to obtain a crystal structure of 2:C60.


(1) Abeyratne Kuragama, P. L.; Fronczek, F. R.; Sygula, A. "Bis-corannulene Receptors for Fullerenes Based on Klärner’s Tethers: Reaching the Affinity Limits," Org. Lett. 2015, ASAP, DOI: 10.1021/acs.orglett.5b02666.

(2) Klärner, F.-G.; Schrader, T. "Aromatic Interactions by Molecular Tweezers and Clips in Chemical and Biological Systems," Acc. Chem. Res. 2013, 46, 967-978, DOI: 10.1021/ar300061c.


1: InChI=1S/C62H34O2/c1-63-61-57-43-23-45(41-21-37-33-17-13-29-9-5-25-3-7-27-11-15-31(35(37)19-39(41)43)53-49(27)47(25)51(29)55(33)53)59(57)62(64-2)60-46-24-44(58(60)61)40-20-36-32-16-12-28-8-4-26-6-10-30-14-18-34(38(36)22-42(40)46)56-52(30)48(26)50(28)54(32)56/h3-22,43-46H,23-24H2,1-2H3/t43-,44+,45+,46-

2: InChI=1S/C66H36O2/c1-67-65-51-24-45-43-23-44(42-20-38-34-16-12-30-8-4-27-3-7-29-11-15-33(37(38)19-41(42)43)59-55(29)53(27)56(30)60(34)59)46(45)25-52(51)66(68-2)64-50-26-49(63(64)65)47-21-39-35-17-13-31-9-5-28-6-10-32-14-18-36(40(39)22-48(47)50)62-58(32)54(28)57(31)61(35)62/h3-22,24-25,43-44,49-50H,23,26H2,1-2H3/t43-,44+,49+,50-

Aromaticity &fullerene &host-guest Steven Bachrach 30 Nov 2015 No Comments

A novel host with two cups that work against each other

Badjic, Hadad, and coworkers have prepared 1 an interesting host molecule that appears like two cups joined at the base, with one cup pointed up and the other pointed down. A slightly simplified analogue 1 of the synthesized host is shown in Figure 1. The actual host is found to bind one molecule of 2, but does not appear to bind a second molecule. Seemingly, only one of the cups can bind a guest, and that this somehow deters a second guest from being bound into the other cup.

Figure 1. B3LYP/6-31G* optimized geometry of host molecule 1. (Visualization of this molecules and the structures below are greatly enhanced by clicking on each image which will invoke the molecular viewer Jmol.)

To address negative allosterism, the authors optimized the structure of 1 at B3LYP/6-31G* (shown in Figure 1). They then optimized the geometry with the constraint that the three arms in the top cup were ever more slightly moved inward. This had the consequential effect of moving the three arms of the bottom cup farther apart. They next optimized (at M06-2x/6-31G(d)) the structures of 1 holding one molecule of guest 2 and with two molecules of guest 2. These structures are shown in Figure 2. In the structure with one guest, the arms are brought in towards the guest for the cup where the guest is bound, and this consequently draws the arms in the other cup to be farther apart, and thereby less capable of binding a second guest. The structure with two guest shows that the arms are not able to get sufficiently close to either guest to form strong non-covalent interactions.

Figure 2. M06-2x/6-31G(d) optimized structures of 1 with one or two molecules of 2.

Thus, the negative allosterism results from a geometric change created by the induced fit of the first guest that results in an unfavorable environment for a second guest.


(1) Chen, S.; Yamasaki, M.; Polen, S.; Gallucci, J.; Hadad, C. M.; Badjić, J. D. "Dual-Cavity Basket Promotes Encapsulation in Water in an Allosteric Fashion," J. Am. Chem. Soc. 2015, 137, 12276-12281, DOI: 10.1021/jacs.5b06041.

host-guest Steven Bachrach 02 Nov 2015 No Comments

Host-guest complexes

Grimme and coworkers have a featured article on computing host-guest complexes in a recent ChemComm.1 They review the techniques his group has pioneered, particularly dispersion corrections for DFT and ways to treat the thermodynamics in moving from electronic energy to free energy. they briefly review some studies done by other groups. They conclude with a new study of eight different host guest complexes, three of which are shown in Figure 1.




Figure 1. TPSS-D3(BJ)/def2-TZVP optimized structures of 1-3.

These eight host-guest complexes are fairly large systems, and the computational method employed means some fairly long computations. Geometries were optimized at TPSS-D3(BJ)/def2-TZVP, then single point energy determined at PW6B95-D3(BJ)/def2-QZVP. Solvent was included using COSMO-RS. The curcurbituril complex 2 includes a counterion (chloride) along with the guest adamantan-1-aminium. Overall agreement of the computed free energy of binding with the experimental values was very good, except for 3 and the related complex having a larger nanohoop around the fullerene. The error is due to problems in treating the solvent effect, which remains an area of real computational need.

An interesting result uncovered is that the binding energy due to dispersion is greater than the non-dispersion energy for all of these complexes, including the examples that are charged or where hydrogen bonding may be playing a role in the bonding. This points to the absolute necessity of including a dispersion correction when treating a host-guest complex with DFT.

As an aside, you’ll note one of the reasons I was interested in this paper: 3 is closely related to the structure that graces the cover of the second edition of my book.


(1) Antony, J.; Sure, R.; Grimme, S. "Using dispersion-corrected density functional theory to understand supramolecular binding thermodynamics," Chem. Commun. 2015, 51, 1764-1774, DOI: 10.1039/C4CC06722C.

Grimme &host-guest Steven Bachrach 12 May 2015 1 Comment

Corannulene bowl inversion inside a host

The concept of complementarity between enzyme and substrate, especially the transition state for reactions at the substrate, is a key element of Pauling’s model for enzymatic activity. Koshland’s “induced fit” modification suggests that the enzyme might change its structure during the binding process to either destabilize the reactant or help stabilize the TS. These concepts are now tested in a very nice model by Stoddart, Siegel and coworkers.1

Stoddart recently reported the host compound ExBox4+ 1 and demonstrated that it binds planar polycyclic aromatic hydrocarbons.2 (I subsequently reported DFT computations on this binding.) The twist in this new paper is the binding of corranulene 2 inside ExBox4+ 1. Corranulene is bowl-shaped, with a bowl inversion barrier of 11.5 kcal mol-1 (10.92 kcal mol-1 at B97D/Def2-TZVPP).

The corranulene bowl is too big to fit directly into 1 without some distortions. The x-ray structure of the complex of 1 with 2 inside shows the width of 1 expanding by 0.87 Å and the bowl depth of 2 decreasing by 0.03 Å. The B97D/Def2-TZVPP optimized geometry of this complex (shown in Figure 1) shows similar distortions – the width of 1 increases by 0.37 Å (gas) or 0.29 Å (acetone solution), while the bowl depth of 2 decreases by 0.03 Å (gas) or 0.02 Å (solution).

ground state

transition state

Figure 1. B97D/Def2-TZVPP optimized geometries of the complex of 2 inside 1 (a) ground state and (b) transition state.

The calculated structure of the bowl inversion transition state of 2 inside of 1 is shown in Figure 1. 2 is planar at the TS. The experimental inversion barrier (determined by variable temperature NMR line shift analysis) is 7.88 kcal mol-1, while the calculated barrier is 8.77 kcal mol-1. The reduction in the bowl inversion barrier of 2 inside of 1 is therefore about 2.5 kcal mol-1. The authors argue that this barrier reduction can be attributed to about 0.5 kcal mol-1 of destabilization of the ground state of 2 along with 2 kcal mol-1 of stabilization of the transition state afforded by the host. This study thus confirms the notions of a host reducing a barrier (through both transition state stabilization and ground state destabilization) and induced fit.


(1) Juríček, M.; Strutt, N. L.; Barnes, J. C.; Butterfield, A. M.; Dale, E. J.; Baldridge, K. K.; Stoddart, J. F.; Siegel, J. S. "Induced-fit catalysis of corannulene bowl-to-bowl inversion," Nat. Chem. 2014, 6, 222-228, DOI: 10.1038/nchem.1842.

(2) Barnes, J. C.; Juríček, M.; Strutt, N. L.; Frasconi, M.; Sampath, S.; Giesener, M. A.; McGrier, P. L.; Bruns, C. J.; Stern, C. L.; Sarjeant, A. A.; Stoddart, J. F. "ExBox: A Polycyclic Aromatic Hydrocarbon Scavenger," J. Am. Chem. Soc. 2012, 135, 183-192, DOI: 10.1021/ja307360n.

(3) Bachrach, S. M. "DFT Study of the ExBox·Aromatic Hydrocarbon Host–Guest Complex," J. Phys. Chem. A 2013, 117, 8484-8491, DOI: 10.1021/jp406823t.


1: InChI=1S/C48H40N4/c1-2-38-4-3-37(1)33-49-25-17-45(18-26-49)41-9-11-43(12-10-41)47-21-29-51(30-22-47)35-39-5-7-40(8-6-39)36-52-31-23-48(24-32-52)44-15-13-42(14-16-44)46-19-27-50(34-38)28-20-46/h1-32H,33-36H2/q+4

2: InChI=1S/C20H10/c1-2-12-5-6-14-9-10-15-8-7-13-4-3-11(1)16-17(12)19(14)20(15)18(13)16/h1-10H

annulenes &host-guest Steven Bachrach 20 Mar 2014 No Comments