Guest control of a hydrogen bond-catalysed molecular rotor

Article abstract of DOI:10.1039/c7cc07672j

Herein, the control of a molecular rotor using hydrogen bonding guests is demonstrated. With a properly positioned phenol substituent, the N-arylimide rotors can form an intramolecular hydrogen bond that catalyses the rotational isomerization process. The

Full text of DOI:10.1039/c7cc07672j

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Marilyn M. Olmstead, Alan L. Balch, Josep M. Poblet, Luis Echegoyenet al.
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Guest control of a hydrogen bond-catalysed molecular rotor
Gregory T. Rushton,a Erik C. Vika, William G. Burns,a Roger D. Rasberry,a and Ken D. Shimizua*
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
Demonstrated is the control of a molecular rotor using rotational barriers above 27 kcal/mol. For example, diether
2
hydrogen bonding guests. With a properly positioned phenol has a rotational barrier of 27.5 kcal/mol and the rotamers can
substituent, the N-arylimide rotors can form an be separated at room temperature using column
intramolecular hydrogen bond that catalyses the rotational chromatography.32 In contrast, diol
1
has a significantly lower
isomerization process. The addition of guests disrupts the rotational barrier of 21.3 kcal/mol and rotates over 10,000
hydrogen bond and raises the rotational barrier slowing times faster than diether 2.
rotation by two orders of magnitude.
R
O
R
O
a)
R
O
O
The design and development of molecular machines
provide exciting new frontiers in synthetic chemistry.1–4 Some
of the most common types are molecular rotors, motors, and
brakes.5–8 Three general strategies have been employed to
control the rates of rotation and rotational barriers of
molecular devices. These include modulating sterics,9–12 bond
order,13,14 and intramolecular hydrogen bonding interactions
of the systems.15–19 This last category allows control of the
molecular rotors and molecular brakes using hydrogen
bonding guests. In most cases, the intramolecular hydrogen
bond slows the rate of rotation, and thus, the addition of a
hydrogen bonding guest that can disrupt the intramolecular
hydrogen bond increases the rate of rotation.15,20 Presented is
a molecular rotor that slows by four orders of magnitude upon
addition of a hydrogen bonding guest via a unique mechanism
of disrupting an intramolecular hydrogen bond that catalyses
the bond rotation. In the absence of guest, the molecular
brake forms the intramolecular hydrogen bond in the
transition state that facilitates and catalyses bond rotation.16–
O
O
O
N
O
N
O
N
O
N
O
O
anti
syn
R
1 (R = H)
2 (R = CH2Ph)
G
b)
H
‡
‡
H O
O
O
N
O
O
N
O
R
R
fast rotation TS
(a) The syn-anti conformational equilibrium for N,N’-
slow rotation TS
Fig.
1
diarylnaphthalene diimide rotamers 1 and 2; and (b) the transitions states
for bond rotation in diol 1 (left) and diol 1 with a hydrogen bonded guest
(right).
Initially, we attributed the difference in rotational barriers
18
to the larger steric presence of the OCH2Ph groups in diether
2
In the course of developing molecular devices based on the
versus the OH groups in diol 1. However, modelling and
atropisomeric N,N’-diaryl naphthalenediimides, we observed
that diol
1
had an unexpectedly low rotational barrier.19–
crystallographic studies found that phenol and benzyl ether
substituents have similar steric profiles because the CH2Ph and
H groups on the oxygens point away from the central
naphthalene diimide spacer (Fig. 1a).32 Thus, an alternate
explanation was examined in which the acidic proton of the
phenol formed an intramolecular hydrogen bond (Fig. 1b) that
stabilized the planar transition state and lowered the
32
This atropisomeric framework forms distinct syn- and anti-
rotamers due to restricted rotation of the N-aryl rotors.
Usually, the rotamers are stable at room temperature with
rotational barrier of diol
bond hypothesis was proposed by Roussel to explain the 5
kcal/mol lower rotational barriers of N-aryl rotors and with
1. A similar intramolecular hydrogen
A
B
ortho-OH groups (Table 1) in comparison to the analogous
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rotors with ortho-OR groups.16,17 Another example is our N-
arylimide molecular brake in which an intramolecular
hydrogen bond in the transition state acts as ‘proton grease’
lowering the rotational barrier by 9.3 kcal/mol.19
Fig. 2 Calculated GS and TS structures (M06-2X/6-31G*) and barrier heights
for the phenol N-arylimide rotors allowed to form (blue lines) or constrained
to prevent (black lines) the formation of intramolecular hydrogen bonds.
The computational studies also enabled examination of
the role of intramolecular hydrogen bonding on the rotational
barrier. In support of our hypothesis, a strong well-defined
hydrogen bond was formed in the transition state (Fig. 2) as
evidenced by an extremely short =O-to-H distance (1.557 Å).
For comparison, the barrier was also calculated for a geometry
in which the OH group was constrained (Fig. 2, black lines) to
point away from the imide carbonyl and was unable to form an
intramolecular hydrogen bond. The barrier for the non-
hydrogen bonding phenol rotor was much higher (26.4
kcal/mol) in comparison to the unconstrained hydrogen
bonding phenol rotor (18.6 kcal/mol). The higher barrier of the
non-hydrogen bonding geometry was very similar to the
benzyl ether rotor (26.4 kcal/mol) confirming that the phenol
were and ether substituents have similar steric effects on the TS in
Table 1 Literature examples of similar N-aryl rotors with lower rotational barriers
for phenol (R = H) versus ether (R = CH3) derivatives.16, 17
OCH3
O
N
RO
RO
S
S
N
N
CH3
CH3
A
B
∆G‡
∆G‡
R = H
20.9 kcal/mol
26.4 kcal/mol
21.0 kcal/mol
25.6 kcal/mol
R = CH3
First, the rotational barriers of diol
1
and diether
2
computationally modelled to verify the presence and influence the absence of a hydrogen bond. This confirmed that the
of an intramolecular hydrogen bond in the planar transition differences in rotational barriers between diol
state. The DFT method M06-2X/6-31G* was selected as it were primarily due to the ability of diol
provides a good balance of accurate steric and hydrogen intramolecular hydrogen bond.
1
1
and diether
2
to form an
bonding energies. The symmetry of the atropisomeric N,N-
diimide platforms enabled analysis of substructure intramolecular hydrogen bond that stabilized the ground state
Interestingly, the phenol rotor could also form an
a
containing a single N-arylimide rotor (Fig. 2), which greatly (Fig. 2). However, this GS hydrogen bond was much weaker
shortened calculation times. A dihedral angle driver was used than the TS hydrogen bond as was evident from its greater
to systematically calculate the energy of structures along the length (1.856 Å) and non-linear geometry (144°).
rotational barrier energy surface (Fig. 3) and the GS and TS Corroboration was provided by a comparison of the ground
structures were identified. The calculated rotational barriers of states and transition states for the constrained and
the phenol and benzyl ether (18.6 and 26.4 kcal/mol) rotors unconstrained systems (Fig. 2, grey arrows). The GS hydrogen
were very similar to the experimental values (21.3 and 27.5 bond was 3.0 kcal/mol; whereas the TS hydrogen bond was
kcal/mol). More importantly, the computational studies were 10.8 kcal/mol.
able to replicate the significantly lower rotational barrier of
the phenol rotor.
The addition of various hydrogen bonding guests, provided
a unique means to control the rotational barrier of diol and
1
also verified the importance of the TS hydrogen bond. Small
molecule guests were used as opposed to changing the bulk
solvent to minimize variations in solvent polarity or viscosity.
The guests compete for and disrupt the intramolecular
hydrogen bond raising the rotational barrier, as shown in Fig.
1b. Small molecule hydrogen bonding guests were selected
with varying hydrogen bond accepting abilities: acetic acid,
acetone, THF, pyridine, triethylamine (TEA), and DMSO.
The rates of rotation were measured by monitoring the
syn/anti ratio of anti-enriched samples of diol
as they approached equilibrium in solution at 18.2 °C and 70.1
°C, respectively. Anti-enriched samples of diol were prepared
by crystallization.32 Anti-enriched samples of diether
were
prepared by treating the anti-enriched diol with benzyl
1 and diether 2
1
2
1
chloride and potassium carbonate in dry DMF at 0 °C.32 All of
the measurements were carried out in a solvent (72:28 (v/v),
benzene-d6:acetonitrile-d3) that would not disrupt the
hydrogen bonding interactions, while yielding distinct peaks in
1
the H NMR spectra for the syn- and anti-conformers of diol
1
and diether
In each case, the addition of the hydrogen bonding guests
(200 equivalents) increased the rotational barrier of diol (Fig.
2.
1
2 | J. Name., 2012, 00, 1-3
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3). By comparison, the rotational barrier for diether
COMMUNICATION
2
did not very low (Ka < 1). Thus, the stabilization of the ground states by
change significantly on addition of 200 equivalents of the same the guests is small or negligible and could not explain the
hydrogen bonding guests. The sharp contrast in the dramatic changes in the rotational barriers in the presence of
sensitivities of diol
bonding guests were consistent with the proposed
mechanisms. For diol the hydrogen bonding guests enabled the reversible turning ON and OFF of the braking
disrupted the TS stabilising intramolecular hydrogen bond effect. For this demonstration, CD2Cl2 was selected as the
raising the rotational barrier. For diether , the hydrogen solvent system so that the polar hydrogen bonding guest
bonding guests have little or no effect on the rotational barrier (DMSO) could be removed by aqueous extraction. The rate of
as diether cannot form an intramolecular hydrogen bond. rotation of a solution of anti-enriched in CD2Cl2 was
1
and diether
2
to the addition of hydrogen these guests.
The dynamic hydrogen bonding interactions of the guests
1,
2
2
1
Quantitative analysis of the effects of each guest provided measured for two complete ON-OFF cycles by adding and
additional support for the role of the intramolecular hydrogen removing DMSO (Fig. 4). Due to the rapid isomerization of diol
bond in diol
1. The measured rotational barriers in the
1 in the absence of guest, this study was started with the brake
presence of each guest were plotted against the hydrogen engaged (with DMSO) and the temperature was kept at -10 °C
bond accepting ability of the guest, as measured by the for the entire experiment. The rate of rotation sped up and
Kamlet-Taft
correlation was observed between the rotational barriers of and then addition of DMSO. After two cycles, the diol reached
diol and the β parameters of the guests. DMSO, which was the syn/anti equilibrium ratio, and the rate of interconversion
the strongest hydrogen bond acceptor in the series, showed could no longer be observed.
the most dramatic effect raising the barrier of diol by 2.3
β parameter (Fig. 3). An excellent linear slowed down by two orders of magnitude with the removal
1
1
250
200
150
100
50
kcal/mol. Weaker hydrogen bond acceptors such as acetic
acid, THF, and acetone had much smaller effects raising barrier
by only 0.6-0.7 kcal/mol.
THF
28
26
24
22
20
AcOH
TEA
DMSO
DMSO
pyridine
no guest
0
-50
without
with
without
with
pyridine
hydrogen bonding guest
AcOH
TEA
Fig. 4 Measured rate constants for a single sample of diol 1 in CD2Cl2 in the
presence (with) and absence (without) 5 eq. of DMSO for two complete
cycles.
THF
acetone
no guest
In conclusion, the rotational barrier of
a
N,N’-
0.35
0.45
0.55
0.65
β
0.75
0.85
diarylnaphthalenediimide molecular rotor can be tuned using
guests with different hydrogen bonding abilities. The key to
this system is the presence of an intramolecular hydrogen
bond in the transition state that catalyses bond rotation. The
guests disrupt the intramolecular hydrogen bond, raising the
rotational barrier. The magnitude of the rate acceleration
could be modulated by the hydrogen bond accepting ability
and number of equivalents of the hydrogen bonding guest. In
future work, we aim to use this rotor as an enzyme model
system to study the role of transition state stabilization by
Fig. 3 Correlation of the measured rotational barriers of diol 1 (diamonds)
and diether 2 (squares) in the presence of 200 eq of guests against the
Kamlet-Taft hydrogen bond accepting parameter (β) of the guests. The
rotational barriers were measured in 72:28 (v/v) benzene-d6:acetonitrile-d3
at 18.2 and 70.1 °C, respectively. The error in the measurements were
within the data markers. Acetone was not tested against diether 2 because
its boiling point is lower than 70.1 °C. The points labelled no guest were
assigned the β of acetonitrile.
hydrogen bonding
.
To test the possibility that the guests were raising the
Acknowledgements
rotational barriers of 1 by hydrogen bonding to and stabilising
the ground state, 1H NMR titration studies were conducted.
This work was supported by NSF grants CHE 1310139 and
1709086.
The measured association constants of DMSO and acetone for
diol
1
in benzene-acetonitrile (72:28, v/v) were 8.9 x 10-1 and
1.0 x 10-2 M-1, respectively. These association constants are
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Graphic Abstract
A molecular rotor is slowed by a hydrogen bonding
guest that disrupts an intramolecular hydrogen bond
that accelerated the rate of rotation.