Crystal Engineering of Supramolecular 1,4-Benzene Bisamides by Side-Chain Modification – Towards Tuneable Anisotropic Morphologies and Surfaces

Benzene bisamides are promising building blocks for supramolecular nano-objects. Their functionality depends on morphology and surface properties. However, a direct link between surface properties and molecular structure itself is missing for this material class. Here, we investigate this interplay for two series of 1,4-benzene bisamides with symmetric and asymmetric peripheral substitution. We elucidated the crystal structures, determined the nano-object morphologies and derived the wetting behaviour of the preferentially exposed surfaces. The crystal structures were solved by combining single-crystal and powder X-ray diffraction, solid-state NMR spectroscopy and computational modelling. Bulky side groups, here t-butyl groups, serve as a structure-directing motif into a packing pattern, which favours the formation of thin platelets. The use of slim peripheral groups on both sides, in our case linear perfluorinated, alkyl chains, self-assemble the benzene bisamides into a second packing pattern which leads to ribbon-like nano-objects. For both packing types, the preferentially exposed surfaces consist of the ends of the peripheral groups. Asymmetric substitution with bulky and slim groups leads to an ordered alternating arrangement of the groups exposed to the surface. This allows the hydrophobicity of the surfaces to be gradually altered. We thus identified two leitmotifs for molecular packings of benzene bisamides providing the missing link between the molecular structure, the anisotropic morphologies and adjustable surface properties of the supramolecular nano-objects.     

Inclusion of neutral guests by water-soluble macrocyclic hosts – a comparative thermodynamic investigation with cyclodextrins,calixarenes and cucurbiturils

Abstract

The driving forces of association between three different families of macrocycles as hosts, namely cyclodextrins (α-, β-, and γ-), p-sulfonatocalix[n]arenes (n = 4–6) as well as cucurbit[n]urils (n = 6–8), and three different bicyclic azoalkane homologues as guests, namely 2,3-diazabicyclo[2.2.1]hept-2-ene (DBH), 2,3-diazabicyclo[2.2.2]oct-2-ene (DBO) as well as 2,3-diazabicyclo[2.2.3]non-2-ene (DBN), were examined by means of calorimetric titrations, NMR spectroscopy and molecular dynamics simulation, all in aqueous solution. The small, spherical and uncharged guests preferably bind inside the cavities of the medium sized hosts. The inclusion complexation by β-cyclodextrin and p-sulfonatocalix[4]arene shows medium binding affinities (millimolar), while cucurbit[7]uril macrocycle shows very strong binding (micromolar). For all types of macrocycles, the complex formation is enthalpically driven (ΔH° < 0), accompanied by slightly unfavourable entropy changes (ΔS° < 0). The results are discussed in terms of the flexibility of the hosts, the hydrophobic character of their cavities and the release of high-energy water upon binding, and generalised by including two additional guests, the ketones cyclopentanone and (+)-camphor.     

Versatile Inclusion Behaviour of a Dinitrocalix[4]arene Having Two Ester Pendants – Preparation and X-ray Crystal Structures of Complexes

An upper-rim dinitro-substituted calix[4]arene possessing two lower-rim ethyl ester pendant groups (1) has been shown to form solid inclusion compounds with acetone (1:1) (1a), DMF (1:1) (1b), DMSO (1:1) (1c) and n-BuOH (2:1) (1d). X-ray crystal structures of the four complexes 1a–d are reported and comparatively discussed, including isostructurality calculations. Although the solid-state conformation of the dinitrocalix[4]arene moiety, stabilized by two intramolecular O–H…O bonds, is maintained in the four inclusion compounds, and all four co-crystals have similar unit cell dimensions and identical space group symmetries, only three of them (1a–c) are homostructural. Depending on the nature of the guest molecule, either the upper or the lower rim site of the calixarene is involved in the complexation, demonstrating either cavitate- or clathrate-type of supramolecular interactions, respectively. Moreover, due to the different guest recognition modes, the calixarene host in 1d is rotated through a non-crystallographic virtual rotation of 180° within the unit cell, in relation to the host molecules in each of the other three homostructural compounds 1a–c, thus giving rise to supramolecular morphotropism – to our knowledge the first case ever described.     

Micro-electromembrane extraction using multiple free liquid membranes and acceptor solutions – Towards selective extractions of analytes based on their acid-base strength

This work investigated selective micro-electromembrane extractions (μ-EMEs) of the colored indicators metanil yellow and congo red (visual proof-of-principle) and the small drug substances nortriptyline, papaverine, mianserin, and citalopram (model analytes) based on their acid-base strength. With two free liquid membranes (FLMs), the target analytes were extracted from aqueous donor solution, across FLM 1 (1-pentanol, 1-ethyl-2-nitrobenzene (ENB) or 4-nitrocumene (4-NC)), into aqueous acceptor solution 1, further across FLM 2 (1-pentanol, ENB or 4-NC), and finally into aqueous acceptor solution 2. All phases had volumes between 1.0 and 1.5 μL and extractions were promoted by 200–300 V d.c. applied across the five-phase μ-EME system formed in a perfluoroalkoxy capillary tubing. The anode was located in acceptor solution 2 and the cathode was located in donor solution for μ-EMEs of acidic analytes, and locations of the electrodes were vice versa for μ-EMEs of basic analytes. After μ-EME, donor solution and acceptor solution 1 and 2 were analyzed by capillary electrophoresis or liquid chromatography-mass spectrometry. The model analytes migrated efficiently in the proposed μ-EME system, their migration behavior was controlled by pH in aqueous solutions and their selective fractionation into acceptor solution 1 and 2 was demonstrated based on their acid-base strength. Under optimal conditions, acceptor solution 2 contained 60% nortriptyline (pK_a = 10.5) and less than 1% papaverine (pK_a = 6.0) and acceptor solution 1 contained 17% nortriptyline and 27% papaverine after 15 min of μ-EME. The five-phase μ-EME system was also compatible with human plasma samples. Work is in progress to further increase the fractionation capability, and to implement the concept into microfluidic platforms.