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Cite this: Phys. Chem. Chem. Phys., 2014, 16, 23854
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Aggregation-induced chiral symmetry breaking of a naphthalimide–cyanostilbene dyad† Xin Li,‡*a Liangliang Zhu,‡b Sai Duan,a Yanli Zhao*c and Hans Ågrena Spontaneously emerged supramolecular chirality and chiral symmetry breaking from achiral/racemic constituents remain poorly understood. We here report that supramolecular chirality may emerge from the structural flexibility of achiral aryl nitrogen centres which provide instantaneous chirality. Employing a naphthalimide–cyanostilbene dyad as a model, we explored the underlying mechanism of aggregationinduced chiral symmetry breaking and found that the conformations of the N-naphthylpiperazine and the N,N-dimethylaniline units facilitate the formation of ordered supramolecular structures and offer
Received 10th September 2014, Accepted 25th September 2014
opposite handedness. Furthermore, chiral symmetry breaking of the monomers was amplified by the
DOI: 10.1039/c4cp04070h
simulations and experimental measurements are thus rationalized by connecting the population of the
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dihedral angles of the aryl nitrogen centres, the morphology of the self-assemblies, and the observed circular dichroism spectra.
formation of dimers. The microscopic and the macroscopic observations from the theoretical
Introduction Chirality constitutes a unique phenomenon in nature and guarantees the outstanding performance of many biomachines of nature that are homochiral.1 It has accordingly been put forward that the future of nanoengineering and material technology may significantly rely on chirality.2 In particular, supramolecular structures formed by self-assembly of small to medium-sized molecules exhibit distinct properties compared to their constituents,3,4 and a number of smart materials with supramolecular chirality and stimuli-responsive properties have been reported for potential applications such as programmable mesoscale hierarchies,5–11 self-assembled luminescent architectures,12–15 and multifunctional tubules, helicates and polymers.16–22 To date, many researchers have employed chiral constituents or inducers to introduce spatial hindrance, thereby facilitating the formation of chirally aligned chromophores.23–26 In the absence of microscopic chiral centres, achiral molecules are expected to form racemic mixtures of left- and right-handed aggregates in solution with no apparent chiral character. However, examples a
Division of Theoretical Chemistry and Biology, School of Biotechnology, KTH Royal Institute of Technology, SE-10691 Stockholm, Sweden. E-mail: [email protected] b Department of Chemistry, Columbia University, New York, New York 10027, USA c Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, 637371, Singapore. E-mail: [email protected] † Electronic supplementary information (ESI) available: Fig. S1–S7. See DOI: 10.1039/c4cp04070h ‡ These authors contributed equally.
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of spontaneously emerged chirality and chiral symmetry breaking from achiral/racemic constituents have been observed, for instance De Rossi and co-workers27 demonstrated that an achiral benzimidocyanine derivative with long alkyl chains could exhibit optical activity upon spontaneous self-assembly into J-aggregates. Moreover, external polarization forces such as stirring vortices have also been shown to induce the formation of chiral aggregates out of achiral species, thus allowing information exchange between the macroscopic world and the microscopic molecules.28,29 Such spontaneous chiral symmetry breaking processes have also been reported in other studies.15,30,31 They remain poorly understood, yet they seem to be of great relevance for separation of chiral enantiomers and formation of enantiopure biomolecules in connection with natural selection of enantiomers. Recently we reported a naphthalimide–cyanostilbene dyad15 (Fig. 1a) which self-assembles in a mixed DMSO/H2O (1 : 9, v/v) solution to give an unexpected bisignate circular dichroism (CD)32,33 signal. This intriguing phenomenon of aggregationinduced CD suggests that supramolecular handedness could spontaneously emerge via aggregation of achiral components in an achiral environment, and an understanding of the spontaneous chiral symmetry breaking may provide knowledge of the natural preference of a specific chiral conformation. It is also of relevance to note that the self-assemblies formed by the naphthalimide–cyanostilbene dyad are of much smaller size (an average cross-sectional diameter of 30 nm)15 compared with those reported to show commingling of linear dichroism (LD) in CD signals.34,35 The nano-sized aggregation is expected to undergo fast tumbling in dilute solution so that the LD effects can be excluded.
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Previous theoretical simulations have provided insight into the interconversion between right- and left-handed helical structures which follows a twisted intermediate state.36,37 These calculations, however, provide limited information on how the chiral symmetry is broken during the formation of aggregates, for instance the cooperative behavior of the monomers and the role of organized solvent structures during aggregation38 have not been addressed. In this paper, we interpret the experimentally observed CD spectra and strive to demystify the aggregation-induced chiral symmetry breaking of the naphthalimide–cyanostilbene dyad in mixed DMSO/H2O (1 : 9) solution by means of molecular dynamics and quantum chemical calculations. We emphasize that the aryl nitrogen centres offer a large flexibility for supramolecular chirality and pave the way for spontaneously emerging chiral conformations.
Computational details Molecular dynamics simulations The geometry of the naphthalimide–cyanostilbene dyad (Fig. 1) was optimized by density functional theory (DFT) calculations employing the hybrid B3LYP functional39 and Pople’s 6-31G* basis set40 as implemented in the Gaussian 09 program.41 At the optimized geometry, electrostatic potentials were computed at the Hartree–Fock level of theory according to the Merz–Singh– Kollman scheme,42 from which the atomic partial charges were derived through the restrained electrostatic potential (RESP) fitting procedure.43 Molecular dynamics (MD) simulations were then performed by the GROMACS program package44 employing the general Amber force field (GAFF)45 and the TIP3P water model.46 Here, the equilibrium bond lengths, bond angles as well as the force constants for the dihedral potentials were further refined so that the molecular mechanical force field could well reproduce the quantum chemically predicted geometries.15 Ten molecules of the naphthalimide–cyanostilbene dyad were first simulated in pure DMSO solvent under constant-NpT conditions (T = 298 K, p = 1 atm) for 10 ns, then 90% of DMSO
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was replaced by water with the same volume and the simulation was continued for 100 ns. Analyses of MD trajectories The computation of solvent-accessible surface area (SASA) involves the whole molecule of the naphthalimide–cyanostilbene dyad, and it can be seen that the magnitude of SASA becomes stable during 40–100 ns. The order parameter was computed for the cyanostilbene and naphthalimide subunits according to literature.47 The long-axis of each chromophore is determined by the eigenvector associated with the smallest eigenvalue of the inertia tensor, and the order parameter of the assembled chromophores is obtained as the largest eigenvalue of the ordering tensor. We then computed the radius of gyration tensor for the self-assembly, which is defined in analogy to the moments of inertia48 2P 2 P 3 P xi xi yi xi zi 7 P 2 P 16 6P 7 S ¼ 6 xi yi yi yi zi 7 5 N4 P P P 2 xi zi yi zi zi where S is the radius of the gyration tensor, N is the number of atoms in the maximal cluster, and {xi, yi, zi} is the position vector of each atom with respect to the centre of mass of the assembly. Diagonalization of S gives the three eigenvalues (l1, l2 and l3) as well as the three effective radii (a, b and c) along the principal axes pffiffiffiffiffiffiffi pffiffiffiffiffiffiffi pffiffiffiffiffiffiffi a ¼ 3l1 ; b ¼ 3l2 ; c ¼ 3l3 The triaxial ellipsoid shape parameter G is determined from a, b and c49 " # 1 a2 þ b2 þ c2 G¼ 5 ðabcÞ2=3 During 40–100 ns the radius of gyration Rg is quite stable with an average value of 1.126 nm. The corresponding parameter G oscillates between 0.6 and 0.75, indicating that the self-assembly is deformed compared with a sphere (ideal G = 0.6). The average values of a, b, and c are 1.393, 1.037, and 0.879 nm, respectively, corresponding to an effective volume of 5.319 nm3. TD-DFT and exciton-coupled matrix method calculations
Fig. 1 (a) Chemical structure and dihedral angles of the naphthalimide– cyanostilbene dyad consisting of the ‘‘N’’ and the ‘‘C’’ units. (b) A snapshot of the self-assembly showing the ‘‘N’’ and the ‘‘C’’ units. (c) Comparison between CD spectra from theoretical calculations using the dipole-velocity and the dipole-length formulae and from experimental measurements.15
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To investigate the circular dichroism of the self-assembly of the naphthalimide–cyanostilbene dyad molecules, we extracted snapshots from the last 60 ns of the assembly from the MD trajectories with an even time interval of 0.5 ns, truncated the alkyl chain which does not contribute to the CD spectra at the wavelength of interest (300–500 nm), and fed the remaining naphthalimide and cyanostilbene monomers into time-dependent (TD) DFT calculations to obtain their transition energies and transition electric/magnetic dipole moments. Single-point TD-DFT calculations were carried out for each chromophore monomer in each snapshot, using the Gaussian 09 program package.41 The hybrid PBE0 functional50 was employed together with
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Dunning’s double-z basis set (denoted as ‘‘D95’’),51 and three excited states were involved in the TD-DFT calculations for each monomer. After TD-DFT calculations of chromophore monomers, the exciton-coupled matrix method52,53 was employed to compute the CD spectra of the self-assembly. The exciton-coupled matrix consists of diagonal elements as excitation energies of the monomers and off-diagonal elements as Coulomb interaction between the transition electric dipole moments of a pair of monomers, and is diagonalized to provide coefficients for linear combinations of the transition electric/magnetic dipole moments of the monomers. The ‘‘TrESP’’ scheme,54 where the electric transition dipole moment is represented by point charges located at each atom, was adopted to compute the off-diagonal elements of the exciton-coupled matrix. Two operator gauges, namely the dipole-velocity and dipole-length formulae, were employed to computed the CD spectra of the self-assembly. The dipolelength approach, on the one hand, is known to be more robust as it converges faster with an increasing size of the basis set; however, the gauge origin of the magnetic dipole operator introduces some arbitrariness when finite basis sets are used. The dipole-velocity approach, on the other hand, is gauge-invariant. Here, our calculations show that the dipole-velocity formalism is more reliable in computing the CD spectra of a snapshot of the ‘‘N’’ unit (see Fig. S2, ESI†).
Results and discussion Aggregation-induced ECD spectra As the bisignate CD signal has been observed in mixed DMSO/ H2O (1 : 9) solution, it is likely that the chiral symmetry of the achiral naphthalimide–cyanostilbene dyad is broken upon aggregation. To verify this hypothesis of spontaneous chiral symmetry breaking, we first carried out a 10 ns MD simulation of ten naphthalimide–cyanostilbene dyad molecules in DMSO, followed by replacement of 90% DMSO by water and a subsequent 100 ns MD simulation of the dyad molecules in the mixed solvents. The ten molecules, which did not form aggregates in pure DMSO, were found to self-assemble into an ordered structure that maximizes the p–p interaction among the chromophores in the mixed DMSO/H2O (1 : 9) solution, as evidenced by the decreased solvent-accessible surface area (SASA) and the increased order parameter (Fig. S1, ESI†). During the MD simulations, the SASA of the naphthalimide– cyanostilbene molecules showed a stepwise decrease with a meta-stable phase during 10–30 ns and a stabilization after 40 ns (Fig. S1a, ESI†). Cluster analysis suggests that all the ten molecules of the naphthalimide–cyanostilbene dyad have aggregated into a full self-assembly. The order parameter of the naphthalimide and cyanostilbene subunits oscillates between 0.2 and 0.8 and finally becomes stable at around 0.65 (Fig. S1b, ESI†), indicating that the self-assembly is flexible with preference of an aligned arrangement of these subunits, facilitating p–p interaction among them. We also monitored the principle components of the radius of the gyration tensor of the assembly
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and found that the largest radius a is around 50% longer than the smallest radius c (Fig. S1c, ESI†), suggesting that the assembly adopts an ellipsoid-like shape which is able to further aggregate into larger fibril-like structures. The triaxial ellipsoid shape parameter G deviates from the ideal 0.6 and suggests that the simulation trajectory during 40–100 ns covers two oscillating periods of the shape of the assembly (Fig. S1d, ESI†). Moreover, the discontinuity of the triaxial radii and parameter G at around 30 ns correspond to the suddenly increased size of the self-assembly. Snapshots of the self-assembly (Fig. 1b) were then extracted from the MD trajectories and fed into subsequent TD-DFT calculations, after which the exciton-coupled matrix method52,53 was employed to compute the CD spectrum (see the ESI† for details). After red-shifting the computed CD spectra by 15 nm to compensate the solvent effects and the inherent deficiency of TD-DFT calculations, good agreement was obtained between theoretical spectra and experimental observations (Fig. 1c). As shown in Fig. 1b, the naphthalimide and cyanostilbene monomers in the snapshot are coloured by their respective CD amplitudes at the longer wavelength (blue = negative; red = positive). It can be seen that the cyanostilbene units in general show stronger CD signals than the naphthalimide units, and that the naphthalimide units tend to reside on the periphery of the assembly surrounding the cyanostilbene units. Steric hindrance of the naphthalimide unit Noticing that the naphthyl piperazine unit may serve as a ‘‘seed’’ of handedness that introduces steric preference in self-assembled supramolecular structures,15 we here describe the spatial conformation of the piperazine unit by defining the dihedral angle oN as the 1-2-3-4 dihedral connecting naphthalene and piperazine (Fig. 1a). Owing to the rigidity of the aromatic naphthalimide unit, the rotation of the oN dihedral angle is the only degree of freedom of the ‘‘N’’ unit (the naphthyl piperazine unit, Fig. 1a) that is able to access many conformations under ambient temperature. As shown in Fig. 2a, the aryl nitrogen atom (N3) adopts a tetrahedral conformation in the optimized geometries of the naphthalimide unit. Such a tetrahedral conformation of the aryl nitrogen is further evidenced by the reported crystal structure of an N-arylpiperazine derivative (Fig. S3, ESI†). The orientation of the two N–C bonds with respect to the aromatic plane leads to a pair of mirror-imaged conformations with instantaneous chirality, as exemplified by the computed CD spectra in Fig. 2b. Here yM refers to the CD amplitude, that is, the peak or trough molar ellipticity of the Cotton band at the longer wavelength (or lower excitation energy). These two instantaneous chiral conformations of the ‘‘N’’ unit exhibit opposite yM and are interchangeable through rotation of the dihedral angle oN. Noteworthily, the rotation of oN is restricted by the steric hindrance between the hydrogen atoms of the naphthalene and the piperazine groups. Owing to such steric hindrance, the probability of oN going beyond the interval of [1651, 301] is almost zero. To reinforce this statement, we have identified several key conformations of the ‘‘N’’ unit at different oN dihedral angles (Fig. 2c). Among these five conformations,
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the ‘‘C’’ unit in order to take into account the instantaneous asymmetric conformations of the N7 atom.
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Monomer and dimer contributions to the ECD spectra
Fig. 2 (a) The two instantaneous chiral conformations of the ‘‘N’’ unit with different oN dihedral angles. (b) Computed CD spectra of the ‘‘N’’ unit in its two instantaneous chiral conformations. (c) Five key conformations (A to E, from left to right) of the ‘‘N’’ unit due to rotation of the oN dihedral angle.
A and C are minima on the potential energy surface, and B is the transition state connecting A and C with a barrier of 8.9 kJ mol1. Noteworthily, A and C belong to the C1 point group and are mirror images of each other, while B belongs to the Cs point group with its symmetry plane coinciding with the naphthalene plane. From conformation C the oN dihedral angle has to overcome a barrier of 55.7 kJ mol1 to reach conformation E, in which the orientation of the piperazine unit is opposite to that in conformation B. Such a high barrier arises from the steric hindrance between the hydrogen atoms on the naphthalene and piperazine groups, and from the non-planarity of the naphthalene (Fig. 2c, conformation D). Similarly, conformation E has to overcome a barrier of 55.7 kJ mol1 to return to conformation A. As a local minimum, conformation E has a potential energy which is 15.1 kJ mol1 higher than the minima A and C, and thus contributes to a negligible 0.23% of the total conformations at ambient temperature according to Boltzmann distribution. Therefore, the oN dihedral angle dominantly resides in the vicinity of the two minima, namely 21.91 and 112.41. Differently, the ‘‘C’’ unit (the N,N-dimethylaniline unit in its Z form, Fig. 1a) possesses more degrees of freedom since it has more single bonds which are allowed to rotate under ambient temperature. We will show in the following sections, however, that only the rotation of the aryl amine unit dominates the CD signal of the ‘‘C’’ unit. In analogy to oN, we define oC as the average of the 5-6-7-8 and the 5 0 -6-7-8 0 dihedral angles of
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We investigated the relationships between the CD signals of chromophore monomers and their geometrical parameters by plotting the CD amplitude yM versus the dihedral angles oN and oC. As shown in Fig. 3a and b, both oN and oC correlate well with the sign and magnitude of yM, while the other rotatable dihedral angles in the ‘‘C’’ unit do not show correlation with yM (Fig. S4, ESI†). We see that an oN larger than 641 leads to a positive yM of the ‘‘N’’ units and vice versa. The positive and negative yM signals of the ‘‘N’’ units are of similar magnitude; however, the unevenly populated oN at a ratio of 64 : 36 leads to a positive yM signal for the ‘‘N’’ units on average. Similarly, oC is unevenly populated at a ratio of 46 : 54 with respect to positive and negative yM for the ‘‘C’’ units. Exception arises when oC is close to 01 or 1801 and when the CD signal arising from the twisting between the methoxylphenyl and cyano groups becomes visible, which nevertheless does not affect the correlation between yM and oC owing to the fact that the population of oC is very small in the vicinity of 01 or 1801. On average, the population of oC leads to a negative yM signal of the ‘‘C’’ units. The averaged CD spectra of the ‘‘N’’ units and the ‘‘C’’ units are of similar magnitude and opposite signs, where the peak of the former is located at a slightly longer wavelength than the trough of the latter (Fig. S5, ESI†). The CD spectra from the monomers of the ‘‘N’’ and the ‘‘C’’ units almost cancel each other and result in a weak CD signal on the magnitude of 103 deg cm2 dmol1. Note that the monomer contribution to the CD spectrum is computed from the instantaneous conformations of the monomers in the aggregated state. Since the sum of monomer contributions to the total CD signal is very small (Fig. S5, ESI†), it is of importance to further analyze the dimer contributions arising from the interaction between the two chromophores. One may suspect that the CD signal of a dimer may significantly rely on the relative positions of the two monomers; however, we did not identify a clear
Fig. 3 (a, b) Dependence of yM on (a) the dihedral angle oN of the ‘‘N’’ unit and (b) the dihedral angle oC of the ‘‘C’’ unit. (c, d) Relative population of (c) oN and (d) oC.
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Fig. 4 (a–c) Dependence of yM signals (in the unit of 105 deg cm2 dmol1) of (a) ‘‘N–N’’ dimer, (b) ‘‘C–C’’ dimer and (c) ‘‘N–C’’ dimer on dihedral angles oN and oC. (d) Comparison between the CD spectra computed by the exciton-coupled matrix method and the corresponding monomer and dimer contributions.
distance-dependence of the yM for the chromophore dimers (Fig. S6, ESI†). A plausible interpretation for the strong yM signal even at a large separation of the two monomers is that the magnitude of yM largely relies on the instantaneous chirality of the two monomers more than on their relative positions. As shown in Fig. 4a, the sign of the CD amplitude yM of an ‘‘N–N’’ dimer is highly correlated with the two oN dihedrals, and the magnitude of yM is amplified by the interaction between the two ‘‘N’’ units. A similar phenomenon was observed for the ‘‘C–C’’ dimers, where yM shows a strong dependence on the two oC dihedral angles (Fig. 4b). Some exceptions arise when both oC are close to 01 or 1801; nonetheless, the probability of oC being close to 01 or 1801 is rather small (Fig. 3d). For the ‘‘N–C’’ dimers a similar pattern is observed for the dependence of yM on oN and oC of the monomers (Fig. 4c). Therefore, the sign and magnitude of the CD amplitude yM of the chromophore dimers are dominated by the two individual dihedral angles oN and oC, indicating that the experimentally observed nonzero CD signals of the self-assembled naphthalimide–cyanostilbene dyad can be directly related to the unevenly populated dihedral angles of the aryl nitrogen centres, namely to the chiral symmetry breaking of the chromophores. To further clarify the contributions of the chromophore monomers and dimers to the total CD spectra, we here define the molar ellipticity contribution by the monomers as X Monomer : yðlÞ ¼ yðlÞA
compared with the total CD spectrum obtained from the exciton-coupled matrix method, while the dimer contribution shows a much better resemblance to the total CD spectrum. The overestimation of the CD spectrum by the dimer contribution suggests non-negligible many-body effects; nonetheless, the dimer contribution constitutes the major part of the CD signals and provides a qualitative agreement with the experimental results. Recalling the dependence of yM on oN and oC, it is clear that the experimentally observed CD spectrum originates from the unevenly populated dihedral angles of the aryl nitrogen centres. Interestingly, we observed that the CD spectra of the ‘‘N’’ decamer and the ‘‘C’’ decamer could be nicely described by their dimer contributions, respectively (Fig. S7, ESI†). From a longer wavelength to a shorter wavelength, the ‘‘N’’ decamer contributes to positive–negative Cotton effects, while the ‘‘C’’ decamer contributes to negative–positive Cotton bands. The ‘‘N’’ units and the ‘‘C’’ units in the self-assembly thus offer opposite handedness to the CD spectra. The CD signals from the ‘‘N’’ decamer and the ‘‘C’’ decamer almost cancel each other, suggesting that the interaction between the ‘‘N’’ and the ‘‘C’’ units provides important contributions to the final CD spectrum. Roles of solvent molecules For a better understanding of the formation mechanism of the self-assembly of the naphthalimide–cyanostilbene dyad, it is of interest to examine the roles of solvent molecules. Here we have carried out MD simulations of the self-assembled naphthalimide– cyanostilbene dyad molecules in a vacuum to investigate the behavior of the self-assembly in the absence of solvent molecules, which is to be compared with that in mixed DMSO/H2O (1 : 9) solution. Analysis of the trajectory shows that the population of oN is quite evenly distributed at the vicinity of 1121 and 221 with a ratio of 47 : 53, which can be attributed to the absence of a polar solvent environment. Recalling that the population of oN at around 221 and 1121 corresponds to the two stable conformations of the ‘‘N’’ unit and that oC populated at around 501 and 1301 corresponds to a diminished conjugation between the p-orbital of the amine and the p-orbital of the phenyl ring of the ‘‘C’’ unit (Fig. 3c and d), we here infer that the oN dihedral angle acts with an instigating role for the conformational change of the self-assemblies, while the oC dihedral angle is passively forced to stay away from its equilibrium region (01 or 1801). Inspection of the structures of the assembly
A
and the molar ellipticity contribution by the dimers as X X X Dimer : yðlÞ ¼ yðlÞA þ yðlÞAB yðlÞA yðlÞB A
A B4A
where A and B are indices of the two chromophores and y(l) is the computed CD spectrum of a monomer or a dimer. As shown in Fig. 4d, the contribution from the monomer is very small
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Fig. 5 (a) Snapshot of the self-assembly with chromophores represented by rods. (b) Computed population of individual oN in vacuum and in mixed DMSO/H2O (1 : 9) solution.
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reveals that the self-assembly is more tightly packed in vacuum with a less ordered structure, as shown in Fig. 5. Differently, in mixed DMSO/H2O (1 : 9) solution the chromophore units are much better aligned, with the peripheral chromophores showing local twisting similar to that observed on the edge of the two-dimensional layered architectures.11 The average oN over the ten molecules in a vacuum and in mixed DMSO/H2O (1 : 9) solution is 641 and 561, respectively, indicating that the polar solvent molecules indeed facilitate chiral symmetry breaking of the self-assembly. Meanwhile, an enhancement in the CH–p interactions36 between the aliphatic chains and the aromatic rings was also observed in vacuum, which has been suggested to be pronounced in the transition state of stereomutation. As such, the disordered structure and the enhanced CH–p interaction in vacuum could lead to racemic mixing of the instantaneous chiral conformations and subsequent suppression of the CD signals. In mixed DMSO/H2O (1 : 9) solution, the highly polar environment enhances the p–p stacking among the aromatic units and facilitates well-ordered conformations of the self-assembly, where the unevenly populated oN dihedral angles stabilize the assembly and give rise to the experimentally observed bisignate CD signals.
Conclusions In summary, we have employed the naphthalimide–cyanostilbene dyad as a model to explore the mechanism behind aggregationinduced chiral symmetry breaking by means of state-of-the-art molecular dynamics simulations and first-principles calculations. The unexpected circular dichroism of the naphthalimide– cyanostilbene dyad aggregation is found to originate from the structural flexibility of the two aryl nitrogen centres which provide instantaneous chirality. The dimers of the chromophores were found to amplify the chiral symmetry breaking of the monomers and to dominantly contribute to the circular dichroism spectrum. The population of the dihedral angles of the aromatic amine units, the morphology of the self-assemblies, and the observed circular dichroism spectra are found to closely relate to each other, thus rationalizing the connection between microscopic and macroscopic observations from theoretical simulations and experimental measurements. We envisage that the elucidation of the unexpected circular dichroism spectra of this self-assembled naphthalimide– cyanostilbene dyad may promote future research in the field and enable further exploration and computer-aided design of materials based on self-assemblies of molecules with intriguing supramolecular chiral character.
Notes and references 1 G. F. Joyce, Nature, 2002, 418, 214–221. 2 V. K. Valev, J. J. Baumberg, C. Sibilia and T. Verbiest, Adv. Mater., 2013, 25, 2517–2534. 3 M. A. Mateos-Timoneda, M. Crego-Calama and D. N. Reinhoudt, Chem. Soc. Rev., 2004, 33, 363–372.
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Cite this: Phys. Chem. Chem. Phys., 2014, 16, 23854
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Aggregation-induced chiral symmetry breaking of a naphthalimide–cyanostilbene dyad† Xin Li,‡*a Liangliang Zhu,‡b Sai Duan,a Yanli Zhao*c and Hans Ågrena Spontaneously emerged supramolecular chirality and chiral symmetry breaking from achiral/racemic constituents remain poorly understood. We here report that supramolecular chirality may emerge from the structural flexibility of achiral aryl nitrogen centres which provide instantaneous chirality. Employing a naphthalimide–cyanostilbene dyad as a model, we explored the underlying mechanism of aggregationinduced chiral symmetry breaking and found that the conformations of the N-naphthylpiperazine and the N,N-dimethylaniline units facilitate the formation of ordered supramolecular structures and offer
Received 10th September 2014, Accepted 25th September 2014
opposite handedness. Furthermore, chiral symmetry breaking of the monomers was amplified by the
DOI: 10.1039/c4cp04070h
simulations and experimental measurements are thus rationalized by connecting the population of the
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dihedral angles of the aryl nitrogen centres, the morphology of the self-assemblies, and the observed circular dichroism spectra.
formation of dimers. The microscopic and the macroscopic observations from the theoretical
Introduction Chirality constitutes a unique phenomenon in nature and guarantees the outstanding performance of many biomachines of nature that are homochiral.1 It has accordingly been put forward that the future of nanoengineering and material technology may significantly rely on chirality.2 In particular, supramolecular structures formed by self-assembly of small to medium-sized molecules exhibit distinct properties compared to their constituents,3,4 and a number of smart materials with supramolecular chirality and stimuli-responsive properties have been reported for potential applications such as programmable mesoscale hierarchies,5–11 self-assembled luminescent architectures,12–15 and multifunctional tubules, helicates and polymers.16–22 To date, many researchers have employed chiral constituents or inducers to introduce spatial hindrance, thereby facilitating the formation of chirally aligned chromophores.23–26 In the absence of microscopic chiral centres, achiral molecules are expected to form racemic mixtures of left- and right-handed aggregates in solution with no apparent chiral character. However, examples a
Division of Theoretical Chemistry and Biology, School of Biotechnology, KTH Royal Institute of Technology, SE-10691 Stockholm, Sweden. E-mail: [email protected] b Department of Chemistry, Columbia University, New York, New York 10027, USA c Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, 637371, Singapore. E-mail: [email protected] † Electronic supplementary information (ESI) available: Fig. S1–S7. See DOI: 10.1039/c4cp04070h ‡ These authors contributed equally.
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of spontaneously emerged chirality and chiral symmetry breaking from achiral/racemic constituents have been observed, for instance De Rossi and co-workers27 demonstrated that an achiral benzimidocyanine derivative with long alkyl chains could exhibit optical activity upon spontaneous self-assembly into J-aggregates. Moreover, external polarization forces such as stirring vortices have also been shown to induce the formation of chiral aggregates out of achiral species, thus allowing information exchange between the macroscopic world and the microscopic molecules.28,29 Such spontaneous chiral symmetry breaking processes have also been reported in other studies.15,30,31 They remain poorly understood, yet they seem to be of great relevance for separation of chiral enantiomers and formation of enantiopure biomolecules in connection with natural selection of enantiomers. Recently we reported a naphthalimide–cyanostilbene dyad15 (Fig. 1a) which self-assembles in a mixed DMSO/H2O (1 : 9, v/v) solution to give an unexpected bisignate circular dichroism (CD)32,33 signal. This intriguing phenomenon of aggregationinduced CD suggests that supramolecular handedness could spontaneously emerge via aggregation of achiral components in an achiral environment, and an understanding of the spontaneous chiral symmetry breaking may provide knowledge of the natural preference of a specific chiral conformation. It is also of relevance to note that the self-assemblies formed by the naphthalimide–cyanostilbene dyad are of much smaller size (an average cross-sectional diameter of 30 nm)15 compared with those reported to show commingling of linear dichroism (LD) in CD signals.34,35 The nano-sized aggregation is expected to undergo fast tumbling in dilute solution so that the LD effects can be excluded.
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Previous theoretical simulations have provided insight into the interconversion between right- and left-handed helical structures which follows a twisted intermediate state.36,37 These calculations, however, provide limited information on how the chiral symmetry is broken during the formation of aggregates, for instance the cooperative behavior of the monomers and the role of organized solvent structures during aggregation38 have not been addressed. In this paper, we interpret the experimentally observed CD spectra and strive to demystify the aggregation-induced chiral symmetry breaking of the naphthalimide–cyanostilbene dyad in mixed DMSO/H2O (1 : 9) solution by means of molecular dynamics and quantum chemical calculations. We emphasize that the aryl nitrogen centres offer a large flexibility for supramolecular chirality and pave the way for spontaneously emerging chiral conformations.
Computational details Molecular dynamics simulations The geometry of the naphthalimide–cyanostilbene dyad (Fig. 1) was optimized by density functional theory (DFT) calculations employing the hybrid B3LYP functional39 and Pople’s 6-31G* basis set40 as implemented in the Gaussian 09 program.41 At the optimized geometry, electrostatic potentials were computed at the Hartree–Fock level of theory according to the Merz–Singh– Kollman scheme,42 from which the atomic partial charges were derived through the restrained electrostatic potential (RESP) fitting procedure.43 Molecular dynamics (MD) simulations were then performed by the GROMACS program package44 employing the general Amber force field (GAFF)45 and the TIP3P water model.46 Here, the equilibrium bond lengths, bond angles as well as the force constants for the dihedral potentials were further refined so that the molecular mechanical force field could well reproduce the quantum chemically predicted geometries.15 Ten molecules of the naphthalimide–cyanostilbene dyad were first simulated in pure DMSO solvent under constant-NpT conditions (T = 298 K, p = 1 atm) for 10 ns, then 90% of DMSO
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was replaced by water with the same volume and the simulation was continued for 100 ns. Analyses of MD trajectories The computation of solvent-accessible surface area (SASA) involves the whole molecule of the naphthalimide–cyanostilbene dyad, and it can be seen that the magnitude of SASA becomes stable during 40–100 ns. The order parameter was computed for the cyanostilbene and naphthalimide subunits according to literature.47 The long-axis of each chromophore is determined by the eigenvector associated with the smallest eigenvalue of the inertia tensor, and the order parameter of the assembled chromophores is obtained as the largest eigenvalue of the ordering tensor. We then computed the radius of gyration tensor for the self-assembly, which is defined in analogy to the moments of inertia48 2P 2 P 3 P xi xi yi xi zi 7 P 2 P 16 6P 7 S ¼ 6 xi yi yi yi zi 7 5 N4 P P P 2 xi zi yi zi zi where S is the radius of the gyration tensor, N is the number of atoms in the maximal cluster, and {xi, yi, zi} is the position vector of each atom with respect to the centre of mass of the assembly. Diagonalization of S gives the three eigenvalues (l1, l2 and l3) as well as the three effective radii (a, b and c) along the principal axes pffiffiffiffiffiffiffi pffiffiffiffiffiffiffi pffiffiffiffiffiffiffi a ¼ 3l1 ; b ¼ 3l2 ; c ¼ 3l3 The triaxial ellipsoid shape parameter G is determined from a, b and c49 " # 1 a2 þ b2 þ c2 G¼ 5 ðabcÞ2=3 During 40–100 ns the radius of gyration Rg is quite stable with an average value of 1.126 nm. The corresponding parameter G oscillates between 0.6 and 0.75, indicating that the self-assembly is deformed compared with a sphere (ideal G = 0.6). The average values of a, b, and c are 1.393, 1.037, and 0.879 nm, respectively, corresponding to an effective volume of 5.319 nm3. TD-DFT and exciton-coupled matrix method calculations
Fig. 1 (a) Chemical structure and dihedral angles of the naphthalimide– cyanostilbene dyad consisting of the ‘‘N’’ and the ‘‘C’’ units. (b) A snapshot of the self-assembly showing the ‘‘N’’ and the ‘‘C’’ units. (c) Comparison between CD spectra from theoretical calculations using the dipole-velocity and the dipole-length formulae and from experimental measurements.15
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To investigate the circular dichroism of the self-assembly of the naphthalimide–cyanostilbene dyad molecules, we extracted snapshots from the last 60 ns of the assembly from the MD trajectories with an even time interval of 0.5 ns, truncated the alkyl chain which does not contribute to the CD spectra at the wavelength of interest (300–500 nm), and fed the remaining naphthalimide and cyanostilbene monomers into time-dependent (TD) DFT calculations to obtain their transition energies and transition electric/magnetic dipole moments. Single-point TD-DFT calculations were carried out for each chromophore monomer in each snapshot, using the Gaussian 09 program package.41 The hybrid PBE0 functional50 was employed together with
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Dunning’s double-z basis set (denoted as ‘‘D95’’),51 and three excited states were involved in the TD-DFT calculations for each monomer. After TD-DFT calculations of chromophore monomers, the exciton-coupled matrix method52,53 was employed to compute the CD spectra of the self-assembly. The exciton-coupled matrix consists of diagonal elements as excitation energies of the monomers and off-diagonal elements as Coulomb interaction between the transition electric dipole moments of a pair of monomers, and is diagonalized to provide coefficients for linear combinations of the transition electric/magnetic dipole moments of the monomers. The ‘‘TrESP’’ scheme,54 where the electric transition dipole moment is represented by point charges located at each atom, was adopted to compute the off-diagonal elements of the exciton-coupled matrix. Two operator gauges, namely the dipole-velocity and dipole-length formulae, were employed to computed the CD spectra of the self-assembly. The dipolelength approach, on the one hand, is known to be more robust as it converges faster with an increasing size of the basis set; however, the gauge origin of the magnetic dipole operator introduces some arbitrariness when finite basis sets are used. The dipole-velocity approach, on the other hand, is gauge-invariant. Here, our calculations show that the dipole-velocity formalism is more reliable in computing the CD spectra of a snapshot of the ‘‘N’’ unit (see Fig. S2, ESI†).
Results and discussion Aggregation-induced ECD spectra As the bisignate CD signal has been observed in mixed DMSO/ H2O (1 : 9) solution, it is likely that the chiral symmetry of the achiral naphthalimide–cyanostilbene dyad is broken upon aggregation. To verify this hypothesis of spontaneous chiral symmetry breaking, we first carried out a 10 ns MD simulation of ten naphthalimide–cyanostilbene dyad molecules in DMSO, followed by replacement of 90% DMSO by water and a subsequent 100 ns MD simulation of the dyad molecules in the mixed solvents. The ten molecules, which did not form aggregates in pure DMSO, were found to self-assemble into an ordered structure that maximizes the p–p interaction among the chromophores in the mixed DMSO/H2O (1 : 9) solution, as evidenced by the decreased solvent-accessible surface area (SASA) and the increased order parameter (Fig. S1, ESI†). During the MD simulations, the SASA of the naphthalimide– cyanostilbene molecules showed a stepwise decrease with a meta-stable phase during 10–30 ns and a stabilization after 40 ns (Fig. S1a, ESI†). Cluster analysis suggests that all the ten molecules of the naphthalimide–cyanostilbene dyad have aggregated into a full self-assembly. The order parameter of the naphthalimide and cyanostilbene subunits oscillates between 0.2 and 0.8 and finally becomes stable at around 0.65 (Fig. S1b, ESI†), indicating that the self-assembly is flexible with preference of an aligned arrangement of these subunits, facilitating p–p interaction among them. We also monitored the principle components of the radius of the gyration tensor of the assembly
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and found that the largest radius a is around 50% longer than the smallest radius c (Fig. S1c, ESI†), suggesting that the assembly adopts an ellipsoid-like shape which is able to further aggregate into larger fibril-like structures. The triaxial ellipsoid shape parameter G deviates from the ideal 0.6 and suggests that the simulation trajectory during 40–100 ns covers two oscillating periods of the shape of the assembly (Fig. S1d, ESI†). Moreover, the discontinuity of the triaxial radii and parameter G at around 30 ns correspond to the suddenly increased size of the self-assembly. Snapshots of the self-assembly (Fig. 1b) were then extracted from the MD trajectories and fed into subsequent TD-DFT calculations, after which the exciton-coupled matrix method52,53 was employed to compute the CD spectrum (see the ESI† for details). After red-shifting the computed CD spectra by 15 nm to compensate the solvent effects and the inherent deficiency of TD-DFT calculations, good agreement was obtained between theoretical spectra and experimental observations (Fig. 1c). As shown in Fig. 1b, the naphthalimide and cyanostilbene monomers in the snapshot are coloured by their respective CD amplitudes at the longer wavelength (blue = negative; red = positive). It can be seen that the cyanostilbene units in general show stronger CD signals than the naphthalimide units, and that the naphthalimide units tend to reside on the periphery of the assembly surrounding the cyanostilbene units. Steric hindrance of the naphthalimide unit Noticing that the naphthyl piperazine unit may serve as a ‘‘seed’’ of handedness that introduces steric preference in self-assembled supramolecular structures,15 we here describe the spatial conformation of the piperazine unit by defining the dihedral angle oN as the 1-2-3-4 dihedral connecting naphthalene and piperazine (Fig. 1a). Owing to the rigidity of the aromatic naphthalimide unit, the rotation of the oN dihedral angle is the only degree of freedom of the ‘‘N’’ unit (the naphthyl piperazine unit, Fig. 1a) that is able to access many conformations under ambient temperature. As shown in Fig. 2a, the aryl nitrogen atom (N3) adopts a tetrahedral conformation in the optimized geometries of the naphthalimide unit. Such a tetrahedral conformation of the aryl nitrogen is further evidenced by the reported crystal structure of an N-arylpiperazine derivative (Fig. S3, ESI†). The orientation of the two N–C bonds with respect to the aromatic plane leads to a pair of mirror-imaged conformations with instantaneous chirality, as exemplified by the computed CD spectra in Fig. 2b. Here yM refers to the CD amplitude, that is, the peak or trough molar ellipticity of the Cotton band at the longer wavelength (or lower excitation energy). These two instantaneous chiral conformations of the ‘‘N’’ unit exhibit opposite yM and are interchangeable through rotation of the dihedral angle oN. Noteworthily, the rotation of oN is restricted by the steric hindrance between the hydrogen atoms of the naphthalene and the piperazine groups. Owing to such steric hindrance, the probability of oN going beyond the interval of [1651, 301] is almost zero. To reinforce this statement, we have identified several key conformations of the ‘‘N’’ unit at different oN dihedral angles (Fig. 2c). Among these five conformations,
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the ‘‘C’’ unit in order to take into account the instantaneous asymmetric conformations of the N7 atom.
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Monomer and dimer contributions to the ECD spectra
Fig. 2 (a) The two instantaneous chiral conformations of the ‘‘N’’ unit with different oN dihedral angles. (b) Computed CD spectra of the ‘‘N’’ unit in its two instantaneous chiral conformations. (c) Five key conformations (A to E, from left to right) of the ‘‘N’’ unit due to rotation of the oN dihedral angle.
A and C are minima on the potential energy surface, and B is the transition state connecting A and C with a barrier of 8.9 kJ mol1. Noteworthily, A and C belong to the C1 point group and are mirror images of each other, while B belongs to the Cs point group with its symmetry plane coinciding with the naphthalene plane. From conformation C the oN dihedral angle has to overcome a barrier of 55.7 kJ mol1 to reach conformation E, in which the orientation of the piperazine unit is opposite to that in conformation B. Such a high barrier arises from the steric hindrance between the hydrogen atoms on the naphthalene and piperazine groups, and from the non-planarity of the naphthalene (Fig. 2c, conformation D). Similarly, conformation E has to overcome a barrier of 55.7 kJ mol1 to return to conformation A. As a local minimum, conformation E has a potential energy which is 15.1 kJ mol1 higher than the minima A and C, and thus contributes to a negligible 0.23% of the total conformations at ambient temperature according to Boltzmann distribution. Therefore, the oN dihedral angle dominantly resides in the vicinity of the two minima, namely 21.91 and 112.41. Differently, the ‘‘C’’ unit (the N,N-dimethylaniline unit in its Z form, Fig. 1a) possesses more degrees of freedom since it has more single bonds which are allowed to rotate under ambient temperature. We will show in the following sections, however, that only the rotation of the aryl amine unit dominates the CD signal of the ‘‘C’’ unit. In analogy to oN, we define oC as the average of the 5-6-7-8 and the 5 0 -6-7-8 0 dihedral angles of
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We investigated the relationships between the CD signals of chromophore monomers and their geometrical parameters by plotting the CD amplitude yM versus the dihedral angles oN and oC. As shown in Fig. 3a and b, both oN and oC correlate well with the sign and magnitude of yM, while the other rotatable dihedral angles in the ‘‘C’’ unit do not show correlation with yM (Fig. S4, ESI†). We see that an oN larger than 641 leads to a positive yM of the ‘‘N’’ units and vice versa. The positive and negative yM signals of the ‘‘N’’ units are of similar magnitude; however, the unevenly populated oN at a ratio of 64 : 36 leads to a positive yM signal for the ‘‘N’’ units on average. Similarly, oC is unevenly populated at a ratio of 46 : 54 with respect to positive and negative yM for the ‘‘C’’ units. Exception arises when oC is close to 01 or 1801 and when the CD signal arising from the twisting between the methoxylphenyl and cyano groups becomes visible, which nevertheless does not affect the correlation between yM and oC owing to the fact that the population of oC is very small in the vicinity of 01 or 1801. On average, the population of oC leads to a negative yM signal of the ‘‘C’’ units. The averaged CD spectra of the ‘‘N’’ units and the ‘‘C’’ units are of similar magnitude and opposite signs, where the peak of the former is located at a slightly longer wavelength than the trough of the latter (Fig. S5, ESI†). The CD spectra from the monomers of the ‘‘N’’ and the ‘‘C’’ units almost cancel each other and result in a weak CD signal on the magnitude of 103 deg cm2 dmol1. Note that the monomer contribution to the CD spectrum is computed from the instantaneous conformations of the monomers in the aggregated state. Since the sum of monomer contributions to the total CD signal is very small (Fig. S5, ESI†), it is of importance to further analyze the dimer contributions arising from the interaction between the two chromophores. One may suspect that the CD signal of a dimer may significantly rely on the relative positions of the two monomers; however, we did not identify a clear
Fig. 3 (a, b) Dependence of yM on (a) the dihedral angle oN of the ‘‘N’’ unit and (b) the dihedral angle oC of the ‘‘C’’ unit. (c, d) Relative population of (c) oN and (d) oC.
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Fig. 4 (a–c) Dependence of yM signals (in the unit of 105 deg cm2 dmol1) of (a) ‘‘N–N’’ dimer, (b) ‘‘C–C’’ dimer and (c) ‘‘N–C’’ dimer on dihedral angles oN and oC. (d) Comparison between the CD spectra computed by the exciton-coupled matrix method and the corresponding monomer and dimer contributions.
distance-dependence of the yM for the chromophore dimers (Fig. S6, ESI†). A plausible interpretation for the strong yM signal even at a large separation of the two monomers is that the magnitude of yM largely relies on the instantaneous chirality of the two monomers more than on their relative positions. As shown in Fig. 4a, the sign of the CD amplitude yM of an ‘‘N–N’’ dimer is highly correlated with the two oN dihedrals, and the magnitude of yM is amplified by the interaction between the two ‘‘N’’ units. A similar phenomenon was observed for the ‘‘C–C’’ dimers, where yM shows a strong dependence on the two oC dihedral angles (Fig. 4b). Some exceptions arise when both oC are close to 01 or 1801; nonetheless, the probability of oC being close to 01 or 1801 is rather small (Fig. 3d). For the ‘‘N–C’’ dimers a similar pattern is observed for the dependence of yM on oN and oC of the monomers (Fig. 4c). Therefore, the sign and magnitude of the CD amplitude yM of the chromophore dimers are dominated by the two individual dihedral angles oN and oC, indicating that the experimentally observed nonzero CD signals of the self-assembled naphthalimide–cyanostilbene dyad can be directly related to the unevenly populated dihedral angles of the aryl nitrogen centres, namely to the chiral symmetry breaking of the chromophores. To further clarify the contributions of the chromophore monomers and dimers to the total CD spectra, we here define the molar ellipticity contribution by the monomers as X Monomer : yðlÞ ¼ yðlÞA
compared with the total CD spectrum obtained from the exciton-coupled matrix method, while the dimer contribution shows a much better resemblance to the total CD spectrum. The overestimation of the CD spectrum by the dimer contribution suggests non-negligible many-body effects; nonetheless, the dimer contribution constitutes the major part of the CD signals and provides a qualitative agreement with the experimental results. Recalling the dependence of yM on oN and oC, it is clear that the experimentally observed CD spectrum originates from the unevenly populated dihedral angles of the aryl nitrogen centres. Interestingly, we observed that the CD spectra of the ‘‘N’’ decamer and the ‘‘C’’ decamer could be nicely described by their dimer contributions, respectively (Fig. S7, ESI†). From a longer wavelength to a shorter wavelength, the ‘‘N’’ decamer contributes to positive–negative Cotton effects, while the ‘‘C’’ decamer contributes to negative–positive Cotton bands. The ‘‘N’’ units and the ‘‘C’’ units in the self-assembly thus offer opposite handedness to the CD spectra. The CD signals from the ‘‘N’’ decamer and the ‘‘C’’ decamer almost cancel each other, suggesting that the interaction between the ‘‘N’’ and the ‘‘C’’ units provides important contributions to the final CD spectrum. Roles of solvent molecules For a better understanding of the formation mechanism of the self-assembly of the naphthalimide–cyanostilbene dyad, it is of interest to examine the roles of solvent molecules. Here we have carried out MD simulations of the self-assembled naphthalimide– cyanostilbene dyad molecules in a vacuum to investigate the behavior of the self-assembly in the absence of solvent molecules, which is to be compared with that in mixed DMSO/H2O (1 : 9) solution. Analysis of the trajectory shows that the population of oN is quite evenly distributed at the vicinity of 1121 and 221 with a ratio of 47 : 53, which can be attributed to the absence of a polar solvent environment. Recalling that the population of oN at around 221 and 1121 corresponds to the two stable conformations of the ‘‘N’’ unit and that oC populated at around 501 and 1301 corresponds to a diminished conjugation between the p-orbital of the amine and the p-orbital of the phenyl ring of the ‘‘C’’ unit (Fig. 3c and d), we here infer that the oN dihedral angle acts with an instigating role for the conformational change of the self-assemblies, while the oC dihedral angle is passively forced to stay away from its equilibrium region (01 or 1801). Inspection of the structures of the assembly
A
and the molar ellipticity contribution by the dimers as X X X Dimer : yðlÞ ¼ yðlÞA þ yðlÞAB yðlÞA yðlÞB A
A B4A
where A and B are indices of the two chromophores and y(l) is the computed CD spectrum of a monomer or a dimer. As shown in Fig. 4d, the contribution from the monomer is very small
23858 | Phys. Chem. Chem. Phys., 2014, 16, 23854--23860
Fig. 5 (a) Snapshot of the self-assembly with chromophores represented by rods. (b) Computed population of individual oN in vacuum and in mixed DMSO/H2O (1 : 9) solution.
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reveals that the self-assembly is more tightly packed in vacuum with a less ordered structure, as shown in Fig. 5. Differently, in mixed DMSO/H2O (1 : 9) solution the chromophore units are much better aligned, with the peripheral chromophores showing local twisting similar to that observed on the edge of the two-dimensional layered architectures.11 The average oN over the ten molecules in a vacuum and in mixed DMSO/H2O (1 : 9) solution is 641 and 561, respectively, indicating that the polar solvent molecules indeed facilitate chiral symmetry breaking of the self-assembly. Meanwhile, an enhancement in the CH–p interactions36 between the aliphatic chains and the aromatic rings was also observed in vacuum, which has been suggested to be pronounced in the transition state of stereomutation. As such, the disordered structure and the enhanced CH–p interaction in vacuum could lead to racemic mixing of the instantaneous chiral conformations and subsequent suppression of the CD signals. In mixed DMSO/H2O (1 : 9) solution, the highly polar environment enhances the p–p stacking among the aromatic units and facilitates well-ordered conformations of the self-assembly, where the unevenly populated oN dihedral angles stabilize the assembly and give rise to the experimentally observed bisignate CD signals.
Conclusions In summary, we have employed the naphthalimide–cyanostilbene dyad as a model to explore the mechanism behind aggregationinduced chiral symmetry breaking by means of state-of-the-art molecular dynamics simulations and first-principles calculations. The unexpected circular dichroism of the naphthalimide– cyanostilbene dyad aggregation is found to originate from the structural flexibility of the two aryl nitrogen centres which provide instantaneous chirality. The dimers of the chromophores were found to amplify the chiral symmetry breaking of the monomers and to dominantly contribute to the circular dichroism spectrum. The population of the dihedral angles of the aromatic amine units, the morphology of the self-assemblies, and the observed circular dichroism spectra are found to closely relate to each other, thus rationalizing the connection between microscopic and macroscopic observations from theoretical simulations and experimental measurements. We envisage that the elucidation of the unexpected circular dichroism spectra of this self-assembled naphthalimide– cyanostilbene dyad may promote future research in the field and enable further exploration and computer-aided design of materials based on self-assemblies of molecules with intriguing supramolecular chiral character.
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