Archive for November, 2015

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

Bistetracene is a biradical singlet

Feng, Müller and co-workers have prepared a bistetracene analogue 1.1 This molecule displays some interesting features. While a closed shell Kekule structure can be written, a biradical structure results in more closed Clar rings, suggesting that perhaps the molecule is a ground state singlet biradical. The loss of NMR signals with increasing temperature along with an EPR signal that increases with temperature both support the notion of a ground state singlet biradical with a triplet excited state. The EPR measurement suggest as singlet-triplet gap of 3.4 kcal mol-1.

The optimized B3LYP/6-31G(d,p) geometries of the biradical singlet and triplet states are shown in Figure 1. The singlet is lower in energy by 6.7 kcal mol-1. The largest spin densities are on the carbons that carry the lone electron within the diradical-type Kekule structures.

singlet 1

triplet 1

Figure 1. B3LYP/6-31G(d,p) optimized geometries of the biradical singlet and triplet states of 1.


(1) Liu, J.; Ravat, P.; Wagner, M.; Baumgarten, M.; Feng, X.; Müllen, K. "Tetrabenzo[a,f,j,o]perylene: A Polycyclic Aromatic Hydrocarbon With An Open-Shell Singlet Biradical Ground State," Angew. Chem. Int. Ed. 2015, 54, 12442-12446, DOI: 10.1002/anie.201502657.


1: InChI=1S/C62H56/c1-33-25-35(3)51(36(4)26-33)53-45-17-13-15-19-47(45)57-56-44-24-22-42(62(10,11)12)30-40(44)32-50-54(52-37(5)27-34(2)28-38(52)6)46-18-14-16-20-48(46)58(60(50)56)55-43-23-21-41(61(7,8)9)29-39(43)31-49(53)59(55)57/h13-32H,1-12H3

Aromaticity &diradicals Steven Bachrach 16 Nov 2015 No Comments

Dynamics in the reaction of tetrazine with cyclopropene

Houk and Doubleday report yet another example of dynamic effects in reactions that appear to be simple, ordinary organic reactions.1 Here they look at the Diels-Alder reaction of tetrazine 1 with cyclopropene 2. The reaction proceeds by first crossing the Diels-Alder transition state 3 to form the intermediate 4. This intermediate can then lose the anti or syn N2, through 5a or 5s, to form the product 6. The structures and relative energies, computed at M06-2X/6-31G(d), of these species are shown in Figure 1.






Figure 1. M06-2X/6-31G(d) optimized geometries and energies (relative to 1 + 2) of the critical points along the reaction of tetrazine with cyclopropene.

The large difference in the activation barriers between crossing 5a and 5s (nearly 9 kcal mol-1) suggests, by transition state theory, a preference of more than a million for loss of the anti N2 over the syn N2. However, quasiclassical trajectory studies, using B3LYP/6-31G(d), finds a different situation. The anti pathway is preferred, but only by a 4:1 ratio! This dynamic effect arises from a coupling of the v3 mode which involves a rocking of the cyclopropane ring that brings a proton near the syn N2 functionality, promoting its ejection. In addition, the trajectory studies find short residence times within the intermediate neighborhood for the trajectories that lead to the anti product and longer residence times for the trajectories that lead to the syn product. All together, a very nice example of dynamic effects playing a significant role in a seemingly straightforward organic reaction.


(1) Törk, L.; Jiménez-Osés, G.; Doubleday, C.; Liu, F.; Houk, K. N. "Molecular Dynamics of the Diels–Alder Reactions of Tetrazines with Alkenes and N2 Extrusions from Adducts," J. Am. Chem. Soc. 2015, 137, 4749-4758, DOI: 10.1021/jacs.5b00014.


1: InChI=1S/C2H2N4/c1-3-5-2-6-4-1/h1-2H

2: InChI=1S/C3H4/c1-2-3-1/h1-2H,3H2

4: InChI=1S/C5H6N4/c1-2-3(1)5-8-6-4(2)7-9-5/h2-5H,1H2

6: InChI=1S/C5H6N2/c1-4-2-6-7-3-5(1)4/h2-5H,1H2

Diels-Alder &Dynamics &Houk Steven Bachrach 09 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