Systematic Dissection of an Aminopyrrolic Cage Receptor for β‐Glucopyranosides Reveals the Essentials for Effective Recognition

A set of structures designed for the recognition of glucosides has been obtained by systematically destructuring a tripodal aminopyrrolic cage receptor that selectively recognizes octyl‐β‐D ‐glucopyranoside (OctβGlc). NMR spectroscopy and isothermal titration calorimetry binding measurements showed that cleavage of one pillar of the cage was beneficial to the binding properties of the receptor, as long as two residual amino groups of the cleaved pillar were present. Removal of these two residual amino groups produced a dramatic loss of affinity for OctβGlc of the resulting monocyclic analogue of the parent cage receptor. A significant improvement in the binding ability was achieved by replacing one pillar with two aminopyrrolic hydrogen‐bonding arms, despite the loss of a preorganized structure. In contrast to the cage receptor, recognition of OctβGlc was observed, even in a competitive medium (30 % DMF in chloroform). Structural studies in solution, carried out through NMR spectroscopy and molecular modeling calculations, led to the elucidation of the 3D binding modes of the side‐armed monocyclic receptors; this highlighted the key role of the amino groups and demonstrated the occurrence of a rotaxane‐like complex, which featured the octyl chain of the glucoside threaded through the macrocyclic ring.     

Self‐Assembly of a Highly Organized,Hexameric Supramolecular Architecture: Formation,Structure and Properties

Two derivatives, ³ L and ⁹ L , of a ditopic, multiply hydrogen‐bonding molecule, known for more than a decade, have been found, in the solid state as well as in solvents of low polarity at room temperature, to exist not as monomers, but to undergo a remarkable self‐assembly into a complex supramolecular species. The solid‐state molecular structure of ³ L , determined by single‐crystal X‐ray crystallography, revealed that it forms a highly organized hexameric entity ³ L ₆ with a capsular shape, resulting from the interlocking of two sets of three monomolecular components, linked through hydrogen‐bonding interactions. The complicated ¹H NMR spectra observed in o‐dichlorobenzene (o‐DCB) for ³ L and ⁹ L are consistent with the presence of a hexamer of D₃ symmetry in both cases. DOSY measurements confirm the hexameric constitution in solution. In contrast, in a hydrogen‐bond‐disrupting solvent, such as DMSO, the ¹H NMR spectra are very simple and consistent with the presence of isolated monomers only. Extensive temperature‐dependent ¹H NMR studies in o‐DCB showed that the L ₆ species dissociated progressively into the monomeric unit on increasing th temperature, up to complete dissociation at about 90 °C. The coexistence of the hexamer and the monomer indicated that exchange was slow on the NMR timescale. Remarkably, no species other than hexamer and monomer were detected in the equilibrating mixtures. The relative amounts of each entity showed a reversible sigmoidal variation with temperature, indicating that the assembly proceeded with positive cooperativity. A full thermodynamic analysis has been applied to the data.     

Absolute Stereochemistry of a 4 a‐Hydroxyriboflavin Analogue of the Key Intermediate of the FAD‐Monooxygenase Cycle

The biological action of flavoenzymes, such as flavin adenine dinucleotide (FAD)‐containing monooxygenase, involves the formation of oxygenated flavin derivatives, such as 4 a‐hydroperoxyflavin and 4 a‐hydroxyflavin, in which a new center of chirality is created at the 4 a position during the enzymatic reactions. So far, the absolute configuration of this center of chirality in natural 4 a‐oxygenated flavins has remained unknown in spite of its key importance for the diverse functions of flavoenzymes. Herein, we report the 4 a‐hydroxy adduct 3 of 3‐benzyl‐5‐ethyl‐10‐(tetraacetyl‐D ‐ribityl)flavinium ( 1 ), one of the key intermediates involved in the enantioselective organocatalytic oxidation of sulfides to sulfoxides. The 4 a‐hydroxyflavin diastereomers (+)‐ 3 and (?)‐ 3 , separated by HPLC, were characterized by electronic circular dichroism (CD) spectroscopy. Their absolute configurations at the 4 a position were, for the first time, determined by comparing experimental CD spectra with those calculated by means of time‐dependent density functional theory (TDDFT) on DFT‐optimized structures obtained after an extensive conformation analysis.     

Highly effective acyclic carbohydrate receptors consisting of aminopyridine, imidazole, and indole recognition units

Neutral imidazole/aminopyridine- and indole/aminopyridine-based receptors, 1 and 2, have been established as highly effective and selective carbohydrate receptors. These receptors effectively recognise neutral carbohydrates through multiple interactions, including neutral hydrogen bonds and CH...pi interactions between the sugar CH groups and the aromatic rings of the receptors. The design of these receptors was inspired by the binding motifs observed in the crystal structures of protein-carbohydrate complexes. The formation of very strong complexes with beta-glucopyranoside 5, beta-maltoside 8, and alpha-maltoside 9 in organic media has been characterised by 1H NMR spectroscopy and confirmed by a second, independent technique, namely fluorescence spectroscopy. The syntheses, molecular-modelling studies, binding properties of the receptors 1 and 2 toward selected mono- and disaccharides as well as comparative binding studies with receptors 3 and 4 are described.     

Parent,Unsubstituted Hemiporphycene: Synthesis and Properties

Among seven possible nitrogen‐in constitutional isomers of porphyrin only one, porphycene, has been obtained so far in the free, unsubstituted form. Herein, the synthesis of another isomer, parent hemiporphycene ( HPc ), and its thorough structural, spectral, photophysical, electrochemical, and theoretical characterization are reported. Most of the properties of HPc are intermediate between those of porphyrin and porphycene, as evidenced by the values of inner‐cavity dimensions, orbital‐energy splittings, absorption coefficients, magnetic circular dichroism parameters, NH‐stretching frequencies, fluorescence quantum yields, tautomerization rates, and redox potentials. The largest differences arise with respect to tautomerism, due to the low symmetry of HPc and inequivalence of the four nitrogen atoms that define the inner cavity. Two trans tautomers are observed, separated in energy by about 1 kcal mol^?1. Tautomerization from the higher‐ to the lower‐energy form is detected in the lowest‐excited singlet state and occurs at a rate that is about four orders of magnitude lower than that observed for porphycene. Hemiporphycene is a very good model for the investigation of inequivalent intramolecular H‐bonds present in one molecule; two such bonds in HPc reveal unusual characteristics, and the bond strength results from the interplay between the N ??? N distance and the N?H?N angle.     

Highly Energetic,Low Sensitivity Aromatic Peroxy Acids

The synthesis, structure, and energetic materials properties of a series of aromatic peroxy acid compounds are described. Benzene‐1,3,5‐tris(carboperoxoic) acid is a highly sensitive primary energetic material, with impact and friction sensitivities similar to those of triacetone triperoxide. By contrast, benzene‐1,4‐bis(carboperoxoic) acid, 4‐nitrobenzoperoxoic acid, and 3,5‐dinitrobenzoperoxoic acid are much less sensitive, with impact and friction sensitivities close to those of the secondary energetic material 2,4,6‐trinitrotoluene. Additionally, the calculated detonation velocities of 3,5‐dinitrobenzoperoxoic acid and 2,4,6‐trinitrobenzoperoxoic acid exceed that of 2,4,6‐trinitrotoluene. The solid‐state structure of 3,5‐dinitrobenzoperoxoic acid contains intermolecular O‐H???O hydrogen bonds and numerous N???O, C???O, and O???O close contacts. These attractive lattice interactions may account for the less sensitive nature of 3,5‐dinitrobenzoperoxoic acid.     

Cation–Cation Pairing by NCH⋅⋅⋅O Hydrogen Bonds

The pairing of ions of opposite charge is a fundamental principle in chemistry, and is widely applied in synthesis and catalysis. In contrast, cation–cation association remains an elusive concept, lacking in supporting experimental evidence. While studying the structure and properties of 4‐oxopiperidinium salts [OC₅H₈NH₂]X for a series of anions X^? of decreasing basicity, we observed a gradual self‐association of the cations, concluding in the formation of an isolated dicationic pair. In 4‐oxopiperidinium bis(trifluoromethylsulfonyl)amide, the cations are linked by N? H???O?C hydrogen bonds to form chains, flanked by hydrogen bonds to the anions. In the tetra(perfluoro‐tert‐butoxy)aluminate salt, the anions are fully separated from the cations, and the cations associate pairwise by N? C? H???O?C hydrogen bonds. The compounds represent the first genuine examples of self‐association of simple organic cations based merely on hydrogen bonding as evidenced by X‐ray structure analysis, and provide a paradigm for an extension of this class of compounds.     

Pulsed gradient spin echo (PGSE) diffusion measurements as a tool for the elucidation of a new type of hydrogen-bonded bicapsular aggregate

Compounds formed by linking two tris(ureidobenzyl)amine modules with a hexamethylene tether are described. These compounds self-assemble to form bicapsular aggregates featuring two rings of six hydrogen-bonded ureas. (1)H and (1)H/(1)H ROESY NMR spectroscopy, together with pulsed gradient spin echo (PGSE) NMR diffusion measurements, have been used to characterize the dimers in solution. The results have been compared with energy-minimized structures. The new compounds are kinetically stable on the NMR timescale, and their thermodynamic stabilities are comparable to other capsular aggregates derived from tris(ureidobenzyl)amines.     

Synthesis, Crystal Structure and Spectrometry Study of Chiral N-Ethyl-N''''-(2'''',3'''',4'''',6''''-tetra-O-acetyl-β-D-glycosyl)-thiocarbamide

1INTRODUCTIONManynomadicsugarsperformimportantbio-logicalfunctions[1].Theycancontrolvariousgeneexpressionstoadjusttheupgrowth,developmentandreactionoforgans[2].Glycosylisothiocyanateshavebeenwidelyusedasvaluableintermediatesinthesynthesisofglycosylderivatives[3].Theiso-thiocyanatesandglycosylisothiocyanateshavebeenthefocusofsyntheticattentionduringrecentyearsbecauseoftheirpotentialpharmacologicalproperties[4].Theyhavealsoattractedconsiderableinterestduetotheanti-HIVactivityshownby1-deoxy…     

Directing Foldamer Self-Assembly with a Cyclopropanoyl Cap

The rational design of self-assembling organic materials is extremely challenging due to the difficulty in precisely predicting solid-state architectures from first principles, especially if synthons are conformationally flexible. A tractable model system to study self-assembly was constructed by appending cyclopropanoyl caps to the N termini of helical α/β-peptide foldamers, designed to form both N−H⋅⋅⋅O and C^α−H⋅⋅⋅O hydrogen bonds, which then rapidly self-assembled to form foldectures (foldamer architectures). Through a combined analytical and computational investigation, cyclopropanoyl capping was observed to markedly enhance self-assembly in recalcitrant substrates and direct the formation of a single intermolecular N−H⋅⋅⋅O/C^α−H⋅⋅⋅O bonding motif in single crystals, regardless of peptide sequence or foldamer conformation. In contrast to previous studies, foldamer constituents of single crystals and foldectures assumed different secondary structures and different molecular packing modes, despite a conserved N−H⋅⋅⋅O/C^α−H⋅⋅⋅O bonding motif. DFT calculations validated the experimental results by showing that the N−H⋅⋅⋅O/C^α−H⋅⋅⋅O interaction created by the cap was sufficiently attractive to influence self-assembly. This versatile strategy to harness secondary noncovalent interactions in the rational design of self-assembling organic materials will allow for the exploration of new substrates and speed up the development of novel applications within this increasingly important class of materials.