Computational design of faster rotating second-generation light-driven molecular motors by control of steric effects

Abstract

We report a systematic computational investigation of the possibility to accelerate the rate-limiting thermal isomerizations of the rotary cycles of synthetic light-driven overcrowded alkene-based molecular motors through modulation of steric interactions.Choosing as reference system a second-generation motor known to accomplish rotary motion in the MHz regime and using density functional theory methods, we propose a three-step mechanism for the thermal isomerizations of this motor and show that variation of the steric bulkiness of the substituent at the stereocenter can reduce the (already small) free-energy barrier of the rate-determining step by a further 15−17 kJ mol -1 . This finding holds promise for future motors of this kind to reach beyond the MHz regime. Furthermore, we demonstrate and explain why one particular step is kinetically favored by decreasing and another step is kinetically favored by increasing the steric bulkiness of this substituent, and identify a possible back reaction capable of impeding the rotary rate.3

Quantum chemical design of rotary molecular motors

“…Then, during the third and final step (via TS3 along the Z pathway; via TS6 along the E pathway), the relative statorrotator folding changes from syn to anti. Importantly, for each system, the isomerizations are markedly exergonic, by about 50 kJ mol 21 for 2 and by 30-90 kJ mol 21 for 2a-2h, [58] which of course favors their completion. Furthermore, in support of the computational procedure, it is encouraging that the calculated rate-determining free-energy barriers of 43 (along the Z pathway) and 40 kJ mol 21 (along the E pathway) for the isomerizations of 2 agree well with the respective experimental estimates [27] of 35 and 34 kJ mol As can be seen, the E !…”

“…[25][26][27][28][50][51][52][53][54][55][56] Encouragingly, this work produced many powerful secondgeneration overcrowded alkenes. [25,27,28] Paralleling the experimental efforts, a series of systematic quantum chemical studies revealed a number of ways to further lower the thermal free-energy barriers of the second-generation motors, [57][58][59] that we now turn to discussing. The starting point for these studies is motor 2 shown in Figure 1, which under suitable experimental irradiation conditions is capable of MHz rotational frequencies.…”

“…While many experimental and computational efforts have been made to improve the thermal isomerization performance of overcrowded-alkene motors, [25][26][27][28][50][51][52][53][54][55][56][57][58][59] it is also important to explore ways to control and modulate their photochemical steps [67][68][69] or the possibility to design new classes of rotary motors whose photochemical steps proceed more efficiently. Through NAMD simulations, [49] it has been inferred that the photoisomerization QYs of overcrowded alkenes are limited (to 0.2-0.3 [68,73] ) by the requirement that the torsional motion around the central olefinic bond in the photoactive first excited singlet state (S 1 ) is coupled to a substantial pyramidalization of one of the carbon atoms, or else the conical intersection (CI) seam with the ground state (S 0 ) cannot be reached.…”

“…[59] Specifically, motors obtained by introducing electron-donating methoxy and dimethylamino (2-EDG in Figure 4B) or electron-withdrawing nitro and cyano (2-EWG in Figure 4B) groups at the stator in conjugation with the central olefinic bond were subjected to DFT calculations of the same type performed in the previous study. [58] Besides 2-EDG and 2-EWG, the analogously substituted motors {2i-EDG, 2f-EDG} and {2i-EWG, 2f-EWG} derived from reference motors 2i and 2f were also considered (see Figure 4B). The results of the calculations, through which the three-step thermal isomerization mechanism outlined in Figure 5 was found to apply also to these additional systems, are presented in Figure 6B.…”

“…Thus, in one of the studies, the stator methoxy and rotator methyl substituents of 2 were replaced with groups of varying steric bulkiness to obtain motors 2a-2d (stator-substituted) and 2e-2h (rotator-substituted) depicted in Figure 4A. [58] In terms of the well-known parameters developed by Taft, [60,61] the bulkiness of the groups considered range from 20.55, 20.55, 20.61, and 21.24 for hydroxyl, methoxy, amino, and methyl to 22.78 for tert-butyl, [62] respectively. Following a series of initial benchmark calculations aimed at identifying a suitable level of DFT for overcrowded alkenes, [57] the thermal syn-(P)-unstable-Z !…”