Conrad Fischer

Fine tuning of crystal architecture by intermolecular interactions: synthon engineering

There has been a long time effort to influence or favourably fine tune structural properties by introduction of substituents or guest molecules of different sizes, shapes and chemical composition to consequently alter physico-chemical properties of the respective crystals. These attempts require the recognition, understanding and application of intermolecular interactions, crystallographic and, in case of occurrence, non-crystallographic symmetries. It brings us to the field of crystal engineering, which aims to produce new substances with required properties based on the knowledge of the structural properties of already characterised solids. A series of calixarene crystal structures are presented where the crystal packing is determined by spatial or by electrostatic effects. A series of laterally substituted calixarenes where both steric requirements and electrostatic forces play a role in the crystal architecture shows how the supramolecular synthon can be engineered.

Conformational behaviour and first crystal structures of a calix[4]arene featuring a laterally positioned carboxylic acid function in unsolvated and solvent-complexed forms

A detailed conformational analysis of a rarely investigated type of compound, a laterally monosubstituted calix[4]arene (1, which has a carboxylic acid function in the lateral position), is reported. 2D solution NMR techniques at various temperatures and in different solvents have been used, showing interesting aggregation behaviour for the different conformers. The first illustrations of crystal structures of this compound type are given, including the unsolvated carboxylic calix[4]arene and two mixed solvent complexes containing EtOH–H2O and EtOH–THF, respectively. Isostructurality calculations have been carried out, allowing detailed comparison of the investigated structures, and an unusual conformational chirality isomerism of the calixarene molecule is demonstrated.

Influence of laterally attached alkyl groups on the conformational behaviour of a basic calix[4]arene: combined NMR, molecular mechanics and X-ray study

Three new calixarenes 3–5 featuring an alkyl residue of different chain lengths attached to one of the central ring methylene groups of the basic calix[4]arene 1 have been prepared. A systematic study that includes also the lower homologous compound 2 showing the effect of the alkyl substitution on the conformational behaviour of the calixarene framework in comparison with the unsubstituted parent compound 1 is reported. The application of special 2D NMR techniques, 2D-EXSY and ROESY methods at various temperatures establishes that calixarenes 2–5 adopt the partial cone conformation of lower symmetry and far less the symmetric cone and 1,2-alternate conformations. In solution, they undergo a fast interconversion with relatively low activation energies of about 15 kcal/mol at room temperature. The conformer distribution is well reproduced by molecular mechanistic calculations (MMFF94), indicating the present conformers to assume the lowest steric energies. A single-crystal X-ray structure of the lateral ethyl derivative 2 corroborates these results, showing the molecule in a sterically favourable partial cone conformation.

Upper rim site lipophilic calix[4]arenes as receptors for natural terpenes and functionally related solvent molecules: combined crystal structure and QMB sensor study

Three upper rim site lipophilic calix[4]arenes 1–3 featuring different para-alkanoyl substituents at the phenolic moieties, i.e.n-hexanoyl, n-octanoyl and 3-cyclohexylpropanoyl groups, are reported to complex, aside from the common solvent molecule n-butanol, different keto and hydroxylic terpene guest molecules such as (−)-menthone, (−)-menthol or (+)-carvone in the solid state. Although for all six inclusion compounds described here, a strict 1 : 1 host : guest stoichiometry is observed, complementary size and polarity relationships between the cone shaped calixarene cavity and the guest molecule emerge from single crystal X-ray structural study. Dependent on the structure of the guest molecule, the calixarenes are arranged in a head-to-head or head-to-tail orientation in the crystalline packing, giving rise to capsular or otherwise deeply enclosed inclusion mode of the guest molecules, respectively. Furthermore, the O-acyl atoms of the calixarenes were found to be directly involved in host–guest interaction. In order to estimate the degree of isostructurality of the host frameworks and to examine the influence of the guest molecules on the solid-state conformation of these calixarene molecules, isostructurality comparison, cell similarity and molecular isometricity calculations were carried out revealing a rare case of supramolecular morphotropism for the pair of (−)-menthone and (−)-menthol inclusions of the n-hexanoyl substituted calixarene. Structure–inclusion property relationship was examined by QMB measurements of thin layers of the calixarenes. Vapor studies with different terpenes and common organic solvents show an increased affinity towards guest molecules with polar functionalities, whereas small solvent molecules like acetone are bound considerably better than the more bulky terpene molecules.

Fine-tuning of packing architecture: symmetrically bridge-disubstituted tetramethoxycalix[4]arenes

Three acetonitrile solvates of tetramethoxycalix[4]arenes equally substituted on opposite methylene bridges are described with respect to their conformation and packing behaviour. All of the host molecules adopt a 1,2-alternate conformation, their packing architecture seems to be affected by the spatial demand of the bridge substituents only. This results in the synthetically implemented fine-tuning of the molecular arrangement. The engineering of the relevant packing motif, the “synthon” may be discussed most appropriate by the term “synthon engineering” following the expression of crystal engineering.

Structural conditions required for the bridge lithiation and substitution of a basic calix[4]arene

Summary Lithiation and subsequent reaction with CO2 was applied to calix[4]arenes with different, equal or mixed, ether functions at the lower-rim site as well as tert-butylated or non-tert-butylated upper-rim positions. Whereas this reaction fails for symmetric calix[4]arene ethers with alkoxy residues greater than methoxy, the carboxylation of mixed methoxy-propoxy calixarene ethers is possible. In connection with this, several new monobridge-substituted calix[4]arenes were characterized with respect to their conformational behaviour in solution and the X-ray crystal structure of one key intermediate is taken into consideration.

5,11,17,23-Tetra-tert-butyl-25,26,27,28-tetra­methoxy­calix[4]arene dichloro­methane hemisolvate

In the title compound, C48H64O4·0.5CH2Cl2, both crystallographically independent calixarene molecules display a partial cone conformation. Their crystal packing is stabilized by C—H⋯π contacts involving the methoxy groups. The solvent molecule is located interstitially between two calixarene units with C—H⋯Cl contacts to methoxy and tert-butyl groups. One tert-butyl residue of each calixarene molecule is disordered over two positions (occupancies 0.60/0.40 and 0.63/0.37), resulting in bond distances that deviate from ideal values. The tetramer calixarene molecules present models with approximate non-crystallographic Cs symmetry.

Bis-calix[4]arene-based podants using the bridge position as a constructive mode of subunit connection

Synthetic pathways for a bridge type connection of two calixarenes by a flexible alkylene chain or a more rigid bistriazole modified connection element of different length are presented. NMR measurements as well as MM calculations point to rather flexible conjugates showing suitable requirements for a potential formation of inclusion complexes with neutral and anionic guests of appropriate size.Graphical Abstract

Crystal structures of benzil monoximes controlled through configurational isomerism, molecular substitution and external complexation

Crystal structures of the configurational isomers of benzil monoxime (1 and 2), a p-methoxy derivative (3) and its solvated species with triethylamine (3a) are reported showing specific influences of the molecular configuration, substitution and solvation on the conformational property and packing behaviour of the molecules. Based on the observed interdependences, in particular involving modes of interaction, potential utilization of the 1,2-dione monoxime functional unit for the purpose of crystal engineering seems promising.

Fluorescent chemosensors based on a new type of lower rim-dansylated and bridge-substituted calix[4]arenes

The synthesis, structural and chemosensing properties of several lower rim-dansylated calix[4]arenes bearing different methylene bridge substituents are described. Compared to bridge-unsubstituted pendants neither the conformational nor the fluorescence characteristics of the calixarene core are perceptibly influenced by the bridge substituent. X-ray structure as well as NMR measurements indicates the lower rim-propoxylated and-dansylated calixarenes to adopt the cone conformation capable of the complexation of Cu2+ ions at micromolar level. Fluorescent measurements point to selective 1:2 calixarene: Cu2+ complex formation with sensing parameters being of a suitable level to make the use as a potentially immobilisable chemosensor for the detection of Cu2+ ions promising.