Dariush Ajami

Synthesis of a Möbius aromatic hydrocarbon.

The defining feature of aromatic hydrocarbon compounds is a cyclic molecular structure stabilized by the delocalization of π electrons that, according to the Hückel rule, need to total 4n + 2 (n = 1,2,…); cyclic compounds with 4n π electrons are antiaromatic and unstable. But in 1964, Heilbronner predicted on purely theoretical grounds that cyclic molecules with the topology of a Möbius band—a ring constructed by joining the ends of a rectangular strip after having given one end half a twist—should be aromatic if they contain 4n, rather than 4n + 2, π electrons. The prediction stimulated attempts to synthesize Möbius aromatic hydrocarbons, but twisted cyclic molecules are destabilized by large ring strains, with the twist also suppressing overlap of the p orbitals involved in electron delocalization and stabilization. In larger cyclic molecules, ring strain is less pronounced but the structures are very flexible and flip back to the less-strained Hückel topology. Although transition-state species, an unstable intermediate and a non-conjugated cyclic molecule, all with a Möbius topology, have been documented, a stable aromatic Möbius system has not yet been realized. Here we report that combining a ‘normal’ aromatic structure (with p orbitals orthogonal to the ring plane) and a ‘belt-like’ aromatic structure (with p orbitals within the ring plane) yields a Möbius compound stabilized by its extended π system.

More Chemistry in Small Spaces

This Account is about coaxing molecules into spaces barely big enough to contain them: encapsulation complexes. In capsules, synthetic modules assemble to fold around their molecular targets, isolate them from the medium for relatively long times, place them in a hydrophobic environment, and present them with functional groups. These arrangements also exist in the interior spaces of biology, and the consequences include the familiar features of enzymes: rapid reactions, stabilization of reactive intermediates, and catalysis. But inside capsules there are phenomena unknown to biology or historical chemistry, including new structures, new stereochemical relationships, and new reaction pathways. In encapsulation complexes, as in architecture, the space that is created by a structure determines what goes on inside. There are constant interactions between the container and contained molecules: encounters are not left to chance; they are prearranged, prolonged, and intense. Unlike architecture, these reversibly formed containers emerge only when a suitable guest is present. The components exist, but they cannot assemble without anything inside. Modifications of the capsule components give rise to the results of the present Account. The focus will be on how seemingly small changes in the encapsulation complexes, exchanging a C═S for a C═O, reducing an angle here and there, or replacing a hydrogen with a methyl, can lead to unexpectedly large differences in behavior.

Compressed alkanes in reversible encapsulation complexes

Simple alkanes feature fully extended conformations as their lowest-energy shapes but can assume coiled, compressed conformations in small spaces. A series of normal alkanes, C(16) to C(19), were encapsulated in self-assembled, hydrogen-bonded complexes. Coiling of the longer alkanes was observed by NMR spectroscopy. The coiling exerts pressure on the interior; the hydrogen bonding seams are loosened, and rotation of the capsules components occurs on the NMR timescale. The rotation results in interconversion of mirror-image capsule assemblies (racemization). The racemization rates were determined and shown to increase with the length of the alkane, the longer alkanes exerting more pressure. Free energies of activation for racemization were determined at the coalescence temperatures, and were ΔG‡ = 15.7, 16.7 and 17.2 kcal mol(-1) for C(19), C(18) and C(17), respectively. The shorter C(16) was encapsulated in its fully extended conformation, and does not seem to exert pressure inside the capsule.

A convenient oxidative deprotection of tetrahydropyranyl ethers with iron(III) nitrate and clay under microwave irradiation in solvent free conditions

Abstract The efficient and environmentally benign oxidative deprotection of tetrahydropyranyl ethers using montmorillonite supported iron(III) nitrate under microwave irradiation under solvent free conditions is described.

“Too Small, Too Big, and Just Right” − Optical Sensing of Molecular Conformations in Self-Assembled Capsules

Irradiation of dimethylbenzil within a cylindrical capsule gives bright green phosphorescence, while irradiation of benzil and dimethoxybenzil in the same capsule results in high energy blue fluorescence. This difference is likely due to the geometric restrictions imposed by the capsules space on its excited guests, forcing a trans-planar conformation in some cases and cis-skewed in others.

Reaction of carboxylic acids and isonitriles in small spaces.

Reversible encapsulation complexes are applied to the reaction of isonitriles with carboxylic acids. Encapsulation facilitates these reactions by amplifying the concentration of reactants, arranging the acid and isonitrile in the appropriate orientations, isolating intermediates from bulk solution, and providing an organized solvent cage.

Disproportionation and self-sorting in molecular encapsulation

Self-assembled capsules are nanoscale structures made up of multiple synthetic subunits held together by weak intermolecular forces. They act as host structures that can completely surround small molecule guests of the appropriate size, shape and chemical surface. Like their biological counterparts, multimeric enzymes and receptors, the subunits of the capsules are generally identical, and lead to homomeric assemblies of high symmetry. In both biological and synthetic systems small variations in structures are tolerated and lead to heteromeric assemblies with slightly different recognition properties. The synthetic capsules are dynamic, with lifetimes from milliseconds to hours, and allow the direct spectroscopic observation of smaller molecules inside, under ambient conditions at equilibrium in solution. We report here the assembly of hybrid capsules made up of 2 very different structures, both capable of forming their own homomeric capsules through hydrogen bonding. These hybrids exhibit host properties that differ markedly from the parent capsules, and suggest that other capsules may emerge from seemingly unrelated modules that have curved surfaces and are rich in hydrogen bonding capabilities.

Adaptations of guest and host in expanded self-assembled capsules

Reversible encapsulation complexes create spaces where two or more molecules can be temporarily isolated. When the mobility of encapsulated molecules is restricted, different arrangements in space are possible, and new forms of isomerism (“social isomerism”) are created: the orientation of one encapsulated molecule influences that of the other in the confined space. Expansion of a capsules length is possible through addition of small-molecule spacer elements. The expanded capsules have dimensions that permit the observation of social isomerism of two identical guests, and they adopt arrangements that properly fill the hosts space. The host also can adapt to longer guests by incorporating additional spacers, much as protein modules are added to a viral capsid in response to larger genomes. Arachidonic and related fatty acid derivatives act in this way to induce the assembly of further extended capsules having sufficient length to accommodate them.

Amplified Halogen Bonding in a Small Space

Weak, intermolecular forces are difficult to observe in solution because the molecular encounters are random, short-lived, and overwhelmed by the solvent. In confined spaces such as capsules and the active sites of enzymes or receptors, the encounters are prolonged, prearranged, and isolated from the medium. We report here the application of encapsulation techniques to directly observe halogen bonding. The small volume of the capsule amplifies the concentrations of both donor and acceptor, while the shape of the space permits their proper alignment. The extended lifetime of the encapsulation complex allows the weak interaction to be observed and characterized by conventional NMR methods under conditions in which the interaction would be negligible in bulk solvent.

Bent Alkanes in a New Thiourea-Containing Capsule

The synthesis of a cavitand featuring thiourea hydrogen bonding sites and its dimerization in the presence of suitable guests are reported. Dimerization creates a capsule host wider than the corresponding urea or imide structures, and longer alkanes can be accommodated. Specifically, n-C(15)H(32) is encapsulated, but this guest appears folded inside as deduced from NMR studies. Apparently, the plasticity of hydrogen bonds between thiourea groups allows a stable encapsulation complex to persist in solution even though the guest is contorted.