Patrick J. M. Stals

Asymmetrically Substituted Benzene‐1,3,5‐tricarboxamides: Self‐Assembly and Odd–Even Effects in the Solid State and in Dilute Solution

Molecular organization: Chiral benzene tricarboxamides with methyl substituents at defined positions self-assemble into supramolecular polymers of preferred helicity by three-fold alpha-helical-type hydrogen bonding. The odd-even effect is operative and all derivatives are liquid crystalline showing a Col(ho) phase (see figure).Asymmetric benzene-1,3,5-tricarboxamides (aBTAs) comprising two n-octyl and one chiral methyl-alkyl side chain were synthesised and characterised. The influence of the position and the configuration of the chiral methyl group (methyl at the alpha, beta or gamma position) in the aliphatic side chains on the liquid-crystalline properties and the aggregation behaviour of the aBTAs was systematically studied and compared to symmetrical benzene-1,3,5-tricarboxamides (sBTAs). Solid-state characterisation (polarised optical microscopy, IR spectroscopy, X-ray diffraction and differential scanning calorimetry) revealed that all aBTAs show threefold, alpha-helical-type intermolecular hydrogen bonding between neighbouring molecules and exhibit a columnar hexagonal organisation from room temperature to well above 200 degrees C. Moving the chiral methyl group closer to the amide group stabilises the liquid-crystalline state, as evidenced by a higher clearing temperature and corresponding enthalpy. The self-assembly of dilute solutions of the aBTAs in methylcyclohexane ( approximately 10(-5) mol L(-1)) was investigated with circular dichroism (CD) spectroscopy. The sign of the Cotton effect demonstrated a pronounced odd-even effect, whereas the value of the molar ellipticity, Deltaepsilon, in the aBTAs was independent of the position of the methyl group. Subsequent temperature-dependent CD measurements showed that the aggregation of all aBTAs can quantitatively be described by the nucleation-growth model and that the stability of the aggregates increases when the chiral methyl group is closer to the amide moiety. The results presented herein illustrate that even small changes in the molecular structure of substituted benzene-1,3,5-tri-carboxamides affect their solid-state properties and their self-assembly behaviour in dilute solutions.

Probing the Limits of the Majority-Rules Principle in a Dynamic Supramolecular Polymer

By systematic variation of the chemical structure of benzene-1,3,5-tricarboxamide (BTA) derivatives, the effect of chemical structure on the amplification of chirality was studied and quantified. In combination with temperature-dependent amplification experiments, the limits of the majority-rules principle were also investigated. For all BTA derivatives a high, constant helix reversal penalty was determined, which is related to the intermolecular hydrogen bonds that are present in all studied derivatives. For asymmetrically substituted BTA derivatives an odd-even effect was found in the degree of chiral amplification when changing the position of the stereogenic center with respect to the amide functionality. It was found that the mismatch penalty could be directly related to the number of stereocenters present in the molecules. Increasing this number from one to three resulted in an increase in this energy penalty while leaving the helix reversal penalty unaffected. For the majority-rules principle this implies that a single stereocenter present in the molecule contains sufficient chiral information at the molecular level to result in a chirally amplified state at the supramolecular level. Further evidence that the mismatch penalty is directly related to the number of stereocenters was obtained from mixed majority-rules experiments where two BTA derivatives with different numbers of stereocenters with opposite stereoconfiguration were studied in a majority-rules experiment. Finally, the ultimate limits of chiral amplification for the majority-rules principle were investigated, revealing that, given a certain helix reversal penalty, there is an optimum to which the mismatch penalty can be reduced while also enhancing the degree of chiral amplification. Temperature-dependent majority-rules experiments could indeed confirm these simulations. These findings show the relevance of both energy penalties when trying to enhance the degree of chiral amplification for the majority-rules principle in a one-dimensional helical supramolecular polymer.

Conformational analysis of supramolecular polymerization processes of disc-like molecules

N,N′,N′′-Trialkylbenzene-1,3,5-tricarboxamides (BTAs) cooperatively self-assemble into one-dimensional, helical supramolecular polymers in apolar alkane solutions. Previous studies revealed that the position and configuration of the methyl group on the aliphatic side-chain gives rise to an ‘odd–even effect’ both in the shape and the sign of the CD-effect. In this study, we elucidate the molecular origin of this odd–even effect by a combination of TD-DFT calculations and spectroscopic experiments. In addition, we observed a pronounced effect of the molecular structure of the alkane solvent on the shape of the Cotton effects and the thermodynamic parameters describing the cooperative supramolecular polymerization. The results revealed a different ability of solvent molecules governed by the shape of their structure to intercalate into the helical stacks, which influences the conformation of the monomer within the supramolecular polymer. The solvent affects the dihedral angle (θ) between the CO group and the benzene central core of the BTA molecule. These findings help to increase a molecular-level understanding of how the solvent controls the conformation of repeating units in a supramolecular system.

How far can we push polymer architectures

We here report the synthesis and characterization of a complex polymeric architecture based on a block copolymer with a cylindrical brush block and a single-chain polymeric nanoparticle block folded due to strong intramolecular hydrogen-bonds. The self-assembly of these constructs on mica surfaces was studied with atomic force microscopy, corroborating the distinct presence of block copolymer architectures.

Dynamic Supramolecular Polymers Based on Benzene-1,3,5-tricarboxamides: The Influence of Amide Connectivity on Aggregate Stability and Amplification of Chirality

N-Centred benzene-1,3,5-tricarboxamides (N-BTAs) composed of chiral and achiral alkyl substituents were synthesised and their solid-state behaviour and self-assembly in dilute alkane solutions were investigated. A combination of differential scanning calorimetry (DSC), polarisation optical microscopy (POM) and X-ray diffraction revealed that the chiral N-BTA derivatives with branched 3,7-dimethyloctanoyl chains were liquid crystalline and the mesophase was assigned as Col(ho). In contrast, N-BTA derivatives with linear tetradecanoyl or octanoyl chains lacked a mesophase and were obtained as crystalline compounds. Variable-temperature infrared spectroscopy showed the presence of threefold, intermolecular hydrogen bonding between neighbouring molecules in the mesophase of the chiral N-BTAs. In the crystalline state at room temperature a more complicated packing between the molecules was observed. Ultraviolet and circular dichroism spectroscopy on dilute solutions of N-BTAs revealed a cooperative self-assembly behaviour of the N-BTA molecules into supramolecular polymers with preferred helicity when chiral alkyl chains were present. Both the sergeants-and-soldiers as well as the majority-rules principles were operative in stacks of N-BTAs. In fact, the self-assembly of N-BTAs resembles closely that of their carbonyl (C=O)-centred counterparts, with the exception that aggregation is weaker and amplification of chirality is less pronounced. The differences in the self-assembly of N- and C=O-BTAs were analysed by density functional theory (DFT) calculations. These reveal a substantially lower interaction energy between the monomeric units in the supramolecular polymers of N-BTAs. The lower interaction energy is due to the higher energy penalty for rotation around the Ph--NH bond compared to the Ph--CO bond and the diminished magnitude of dipole-dipole interactions. Finally, we observed that mixed stacks are formed in dilute solution when mixing N-BTAs and C=O BTAs.

Hydrogen Bonding Directed Supramolecular Polymerisation of Oligo(Phenylene‐Ethynylene)s: Cooperative Mechanism, Core Symmetry Effect and Chiral Amplification

The design of supramolecular motifs with tuneable stability and adjustable supramolecular polymerisation mechanisms is of crucial importance to precisely control the properties of supramolecular assemblies. This report focuses on constructing π-conjugated oligo(phenylene ethynylene) (OPE)-based one-dimensional helical supramolecular polymers that show a cooperative growth mechanism. Thus, a novel set of discotic molecules comprising a rigid OPE core, three amide groups, and peripheral solubilising wedge groups featuring C(3) and C(2) core symmetry was designed and synthesised. All of the discotic molecules are crystalline compounds and lack a columnar mesophase in the solid state. In dilute methylcyclohexane solution, one-dimensional supramolecular polymers are formed stabilised by threefold intermolecular hydrogen bonding and π-π interactions, as evidenced by (1)H NMR measurements. Small-angle X-ray and light scattering measurements reveal significant size differences between the columnar aggregates of C(3)- and C(2)-symmetrical discotics, that is, the core symmetry strongly influences the nature of the supramolecular polymerisation process. Temperature-dependent CD measurements show a highly cooperative polymerisation process for the C(3)-symmetrical discotics. In contrast, the self-assembly of C(2)-symmetrical discotics shows a smaller enthalpy release upon aggregation and decreased cooperativity. In all cases, the peripheral stereogenic centres induce a preferred handedness in the columnar helical aggregates. Moreover, one stereogenic centre suffices to fully bias the helicity in the C(2)-symmetrical discotics. Finally, chiral amplification studies with the C(3)-symmetrical discotics were performed by mixing chiral and achiral discotics (sergeants-and-soldiers experiment) and discotics of opposite chirality (majority-rules experiment). The results demonstrate a very strong sergeants-and-soldiers effect and a rather weak majority-rules effect.

Symmetry Breaking in the Self‐Assembly of Partially Fluorinated Benzene‐1,3,5‐tricarboxamides

The interplay of two subsequent aggregation processes results in a symmetry-breaking phenomenon in an achiral self-assembling system. Partially fluorinated benzene-1,3,5-tricarboxamide molecules self-assemble into a racemic mixture of one-dimensional P- and M-helical aggregates, followed by bundling into optically active higher-order aggregates or fibers.

The balance between intramolecular hydrogen bonding, polymer solubility and rigidity in single-chain polymeric nanoparticles

A library of copolymers with pendant, protected ureido-pyrimidinone (UPy) groups was prepared applying controlled polymerization techniques. The polymer backbones were based on polyacrylate, polymethacrylate, polystyrene and polynorbornene and differ in stiffness, molecular weight and the linking moiety between the backbone and the UPy group. In all cases, the percentage of protected UPy groups was kept constant. The effect of solvent on the behaviour of the polymers before and after removal of the protecting groups was evaluated in, among others, chloroform and tetrahydrofuran (THF). After deprotection of the UPy protecting group, the UPys dimerize via four-fold H-bonding in THF, inducing a collapse into single-chain polymeric nanoparticles (SCPNs), as evidenced by a combination of 1H-NMR spectroscopy, size-exclusion chromatography and dynamic light scattering. In chloroform, on the other hand, dimerization of the UPy groups is present but interchain interactions occur as well, resulting in less-defined SCPNs. Remarkably, the flexibility of the polymer backbone, the polymer molecular weight and the nature of the linker unit all do not affect SCPN formation. In contrast, the interaction between solvent and the UPy moiety is a critical parameter for SCPN formation. For example, strong intramolecular dimerization of the UPys is observed in THF while interparticle interactions are suppressed. From this investigation we conclude that a wide variety of polymer backbones are suitable for polymer collapse via supramolecular interactions and thus allow for the formation of SCPNs but that the solvent choice is crucial to enhance intramolecular H-bonding and, at the same time, to suppress interparticle interactions.

The influence of oligo(ethylene glycol) side chains on the self-assembly of benzene-1,3,5-tricarboxamides in the solid state and in solution

Substituted benzene-1,3,5-tricarboxamides (BTAs) 1–4 comprising polar tetraethyleneglycol (tetraEG) and/or apolar (R)-3,7-dimethyloctyl side chains were synthesised and their self-assembly in the solid state and in solution was investigated. While BTA 1 (comprising 3 apolar side chains) shows helical columnar packing via threefold α-helical type intermolecular hydrogen bonding in the solid state and up to high dilutions in alkane solution (10−5 M), helical columnar order is only preserved for asymmetric BTA 2 (comprising 1 polar and 2 apolar side chains) in the solid state and in a concentrated alkane solution (10−2 M). The association constant Kass is reduced by a factor of 107 by introducing one polar tetraEG chain into the BTA. A further increase in the number of polar tetraEG chains attached to BTA core results in the complete loss of intermolecular hydrogen bond formation in the solid state and in solution. Moreover, for the polar BTAs 3–4, comprising 2 or 3 polar tetraEG chains, no self-assembly in water occurs because of the lack of hydrophobic shielding. We propose that tetraEG side chains interfere with the intermolecular hydrogen bonds, weakening the stacking behaviour of these asymmetric derivatives and drastically lowering the association constant due to competing intramolecular hydrogen bonding interactions. In contrast, one methoxyethyl unit does not affect the stability of the aggregation of BTAs (Kass = 3 × 107 M−1) showing that more than one EG unit is required to disrupt the self-assembly of BTAs.

Unusual Analyte-Matrix Adduct Ions and Mechanism of Their Formation in MALDI TOF MS of Benzene-1,3,5-Tricarboxamide and Urea Compounds

AbstractAnalyte-matrix adducts are normally absent under typical matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI TOF MS) conditions. Interestingly, though, in the analysis of several types of organic compounds synthesized in our laboratory, analyte-matrix adduct ion peaks were always recorded when common MALDI matrices such as 4-hydroxy-α-cyanocinnamic acid (CHCA) were used. These compounds are mainly those with a benzene-1,3,5-tricarboxamide (BTA) or urea moiety, which are important building blocks to make new functional supramolecular materials. The possible mechanism of the adduct formation was investigated. A shared feature of the compounds studied is that they can form intermolecular hydrogen bonding with matrices like CHCA. The intermolecular hydrogen bonding will make the association between analyte ions and matrix molecules stronger. As a result, the analyte ions and matrix molecules in MALDI clusters will become more difficult to be separated from each other. Furthermore, it was found that analyte ions were mainly adducted with matrix salts, which is probably due to the much lower volatility of the salts compared with that of their corresponding matrix acids. It seems that the analyte-matrix adduct formation for our compounds are caused by the incomplete evaporation of matrix molecules from the MALDI clusters because of the combined effects of enhanced intermolecular interaction between analyte-matrix and of the low volatility of matrix salts. Based on these findings, strategies to suppress the analyte-matrix adduction are briefly discussed. In return, the positive results of using these strategies support the proposed mechanism of the analyte-matrix adduct formation. ᅟ