Breaking Radial Dipole Symmetry in Planar Macrocycles Modulates Edge-to-Edge Packing and Disrupts Cofacial Stacking.

Dipolar interactions are ever-present in supramolecular architectures, though their impact is typically revealed by making dipoles stronger. While it is also possible to assess the role of dipoles by altering their orientations by using synthetic design, doing so without altering the molecular shape is not straightforward. We have now done this by flipping one triazole unit in a rigid macrocycle, tricarb. The macrocycle is composed of three carbazoles (2 Debye) and three triazoles (5 Debye) defining an array of dipoles aligned radially but organized alternately in and out. These dipoles are believed to dictate edge-to-edge tiling and face-to-face stacking. We modified our synthesis to prepare isosteric macrocycles with the orientation of one triazole dipole rotated 40°. The new dipole orientation guides edge-to-edge contacts to reorder the stability of two surface-bound 2D polymorphs. The impact on dipole-enhanced π stacking, however, was unexpected. Our stacking model identified an unchanged set of short-range (3.4 Å) anti-parallel dipole contacts. Despite this situation, the reduction in self-association was attributed to long-range (~6.4 Å) dipolar repulsions between π-stacked macrocycles. This work highlights our ability to control the build-up and symmetry of macrocyclic skeletons by synthetic design, and the work needed to further our understanding of how dipoles control self-assembly.

Solvent Acts as the Referee in a Match-Up Between Charged and Preorganized Receptors.

The prevalence of anion-cation contacts in biomolecular recognition under aqueous conditions suggests that ionic interactions should dominate the binding of anions in solvents across both high and low polarities. Investigations of this idea using titrations in low polarity solvents are impaired by interferences from ion pairing that prevent a clear picture of binding. To address this limitation and test the impact of ion-ion interactions across multiple solvents, we quantified chloride binding to a cationic receptor after accounting for ion pairing. In these studies, we created a chelate receptor using aryl-triazole CH donors and a quinolinium unit that directs its cationic methyl inside the binding pocket. In low-polarity dichloromethane, the 1 : 1 complex (log K1 : 1 ~ 7.3) is more stable than neutral chelates, but fortuitously comparable to a preorganized macrocycle (log K1 : 1 ~ 6.9). Polar acetonitrile and DMSO diminish stabilities of the charged receptor (log K1 : 1 ~ 3.7 and 1.9) but surprisingly 100-fold more than the macrocycle. While both receptors lose stability by dielectric screening of electrostatic stability, the cationic receptor also pays additional costs of organization. Thus even though the charged receptor has stronger binding in apolar solvents, the uncharged receptor has more anion affinity in polar solvents.

Sequence-Defined Macrocycles for Understanding and Controlling the Build-up of Hierarchical Order in Self-Assembled 2D Arrays.

Anfinsen's dogma that sequence dictates structure is fundamental to understanding the activity and assembly of proteins. This idea has been applied to all manner of oligomers but not to the behavior of cyclic oligomers, aka macrocycles. We do this here by providing the first proofs that sequence controls the hierarchical assembly of nonbiological macrocycles, in this case, at graphite surfaces. To design macrocycles with one (AAA), two (AAB), or three (ABC) different carbazole units, we needed to subvert the synthetic preferences for one-pot macrocyclizations. We developed a new stepwise synthesis with sequence-defined targets made in 11, 17, and 22 steps with 25, 10, and 5% yields, respectively. The linear build up of primary sequence (1°) also enabled a thermal Huisgen cycloaddition to proceed regioselectively for the first time using geometric control. The resulting macrocycles are planar (2° structure) and form H-bonded dimers (3°) at surfaces. Primary sequences encoded into the suite of tricarb macrocycles were shown by scanning-tunneling microscopy (STM) to impact the next levels of supramolecular ordering (4°) and 2D crystalline polymorphs (5°) at solution-graphite interfaces. STM imaging of an AAB macrocycle revealed the formation of a new gap phase that was inaccessible using only C3-symmetric macrocycles. STM imaging of two additional sequence-controlled macrocycles (AAD, ABE) allowed us to identify the factors driving the formation of this new polymorph. This demonstration of how sequence controls the hierarchical patterning of macrocycles raises the importance of stepwise syntheses relative to one-pot macrocyclizations to offer new approaches for greater understanding and control of hierarchical assembly.

Amphiphile self-assembly dynamics at the solution-solid interface reveal asymmetry in head/tail desorption.

Amphiphilic alkoxybenzonitriles (ABNs) of varying chain length are studied at the solution/graphite interface to analyze dynamics of assembly. Competitive self-assembly between ABNs and alkanoic acid solvent is shown by scanning tunneling microscopy (STM) to be controlled by concentration and molecular size. Molecular dynamics (MD) simulations reveal key roles of the sub-nanosecond fundamental steps of desorption, adsorption, and on-surface motion. We discovered asymmetry in desorption-adsorption steps. Desorption starting from alkyl chain detachment from the surface is favored due to dynamic occlusion by neighbouring chains. Even though the nitrile head has a strong solvent affinity, it more frequently re-adsorbs following a detachment event.

Host-Host Interactions Control Self-assembly and Switching of Triple and Double Decker Stacks of Tricarbazole Macrocycles Co-assembled with anti-Electrostatic Bisulfate Dimers.

Hierarchical assembly provides a route to complex architectures when using building blocks with strong and structurally well-defined recognition elements. These rules are traditionally expressed using cationic templates with reliable metal-ligand bonding but use of anions is rare on account of weak anion-host contacts. We investigate an approach that relies on host-host interactions to fortify assemblies formed between bisulfate anion dimers, [HSO4⋅⋅⋅HSO4]2- , and shape-persistent macrocycles called tricarbazole triazolophanes. These macrocycles have significant self-association. In chloroform, they form high fidelity, triple-decker stacks with bisulfate dimers. The strength of host-host interactions allows for preferential formation of the 3:2 tricarb:bisulfate architecture over an ion-paired architecture seen with analogous macrocycles with much weaker self-association. Solvent was expected and found to tune host-host contacts enabling formation of a 2:2 complex and solvent-driven switching between triple- and double-stacked structures. Crystallography of the 2:2:2 complex supports the idea that significant host-host interactions with tricarb arises from dipole-stabilized π-stacking. Computational studies were also conducted further highlighting the importance of host-host interactions in stacked complexes of tricarb. These findings unambiguously verify the importance of host-host interactions in the assembly and stability of discrete, responsive anion-templated architectures.

Multifunctional Tricarbazolo Triazolophane Macrocycles: One-Pot Preparation, Anion Binding, and Hierarchical Self-Organization of Multilayers.

Programming the synthesis and self-assembly of molecules is a compelling strategy for the bottom-up fabrication of ordered materials. To this end, shape-persistent macrocycles were designed with alternating carbazoles and triazoles to program a one-pot synthesis and to bind large anions. The macrocycles bind anions that were once considered too weak to be coordinated, such as PF6 (-) , with surprisingly high affinities (ß2 =10(11) M(-2) in 80:20 chloroform/methanol) and positive cooperativity, α=(4 K2 /K1 )=1200. We also discovered that the macrocycles assemble into ultrathin films of hierarchically ordered tubes on graphite surfaces. The remarkable surface-templated self-assembly properties, as was observed by using scanning tunneling microscopy, are attributed to the complementary pairing of alternating triazoles and carbazoles inscribed into both the co-facial and edge-sharing seams that exist between shape-persistent macrocycles. The multilayer assembly is also consistent with the high degree of molecular self-association observed in solution, with self-association constants of K=300 000 M(-1) (chloroform/methanol 80:20). Scanning tunneling microscopy data also showed that surface assemblies readily sequester iodide anions from solution, modulating their assembly. This multifunctional macrocycle provides a foundation for materials composed of hierarchically organized and nanotubular self-assemblies.