Search

We report Pd‐catalyzed cyclotrimerization of (+)‐α‐bromoenone, obtained from monoterpene β‐pinene, into an enantiopure cyclotrimer. This C3 symmetric compound has three bicyclo[3.1.1]heptane rings fused to its central benzene with each ring carrying a carbonyl group. The cyclotrimer undergoes diastereoselective threefold alkynylation with the lithium salts of five terminal alkynes (41–63 %, de=4–83 %). The addition enabled a rapid synthesis of a small library of novel chiral cavitands that, in shape, resemble a tripod stand. These molecular tripods include a tris‐bicycloannelated benzene head attached to three alkyne legs twisted in one direction to form a nonpolar cavity with polar groups as feet. Tripods with methylpyridinium and methylisoquinolinium legs, respectively, form inclusion complexes with anti‐inflammatory and chiral drugs (R)/(S)‐ibuprofen and (R)/(S)‐naproxen. The mode of binding shows drug molecules docked in the cavity of the host through ion‐ion, cation‐π, and C−H−π contacts that, in addition of desolvation, give rise to complexes having millimolar to micromolar stability in water. Our findings open the door to creating a myriad of enantiopure tripods with tunable functions that, in the future, might give novel chemosensors, catalysts or sequestering agents. [ABSTRACT FROM AUTHOR]

Two limiting cases of molecular recognition, induced fit (IF) and conformational selection (CS), play a central role in allosteric regulation of natural systems. The IF paradigm states that a substrate "instructs" the host to change its shape after complexation, while CS asserts that a guest "selects" the optimal fit from an ensemble of preexisting host conformations. With no studies that quantitatively address the interplay of two limiting pathways in abiotic systems, we herein and for the first time describe the way by which twisted capsule M‐1, encompassing two conformers M‐1(+) and M‐1(−), trap CX4 (X=Cl, Br) to give CX4⊂M‐1(+) and CX4⊂M‐1(−), with all four states being in thermal equilibrium. With the assistance of 2D EXSY, we found that CBr4 would, at its lower concentrations, bind M‐1 via a M‐1(+)→M‐1(−)→CBr4⊂M‐1(−) pathway corresponding to conformational selection. For M‐1 complexing CCl4 though, data from 2D EXSY measurements and 1D NMR line‐shape analysis suggested that lower CCl4 concentrations would favor CS while the IF pathway prevailed at higher proportions of the guest. Since CS and IF are not mutually exclusive, we reason that our work sets the stage for characterizing the dynamics of a wide range of already existing hosts to broaden our fundamental understanding of their action. The objective is to master the way in which encapsulation takes place for designing novel and allosteric sequestering agents, catalysts and chemosensors akin to those found in nature. [ABSTRACT FROM AUTHOR]

Covalent capsule 1 was designed to include two molecular baskets linked with three mobile pyridines tucked into its inner space. On the basis of both theory (DFT) and experiments (NMR and X‐ray crystallography), we found that the pyridine "doors" split the chamber (380 Å3) of 1 so that two equally sizeable compartments (190 Å3) became joined through a conformationally flexible aromatic barrier. The compartments of such unique host could be populated with CCl4 (88 Å3; PC=46 %), CBr4 (106 Å3; 56 %) or their combination CCl4/CBr4 (PC=51 %), with thermodynamic stabilities ΔG° tracking the values of packing coefficients (PC). Halogen (C−X⋅⋅⋅π) and hydrogen bonding (C−H⋅⋅⋅X) contacts held the haloalkane guests in the cavities of 1. The consecutive complexations were found to occur in a negative allosteric manner, which we propose to result from the induced‐fit mode of complexation. Newly designed 1 opens a way for probing the effects of inner conformational dynamics on noncovalent interactions, reactivity and intramolecular translation in confined spaces of hollow molecules. [ABSTRACT FROM AUTHOR]

Discovering novel and functional photoresponsive materials is of interest for improving controlled release of molecules and scavenging toxic compounds for cleaning our environment or designing chemosensors. In this study, we report on the photoinduced decarboxylation of basket 16−, containing three glutamic acids at its rim. This concave compound is, in an aqueous environment (30 mm phosphate buffer at pH 7.0), monomeric (1H NMR DOSY, DLS) with glutamic acid residues randomly oriented about its rim (1H NMR and MM‐OPLS3). The irradiation (300 nm) of 16− leads to the exclusive removal of its α‐carboxylates to give amphiphilic 23− possessing γ‐carboxylates. The photochemical transformation is a consecutive reaction with mono‐ and bis‐decarboxylated products observed with 1H NMR spectroscopy and ESI mass spectrometry. Amphiphilic 23− is a preorganized molecule (MM‐OPLS3) that, in water, aggregates into organic nanoparticles (ca. 50–200 nm in diameter; DLS, TEM and cryo‐TEM) having a critical aggregation concentration of 12 μm (UV/Vis). As the transition of monomeric 16− into nanoparticulate 23− is triggered with light, we reasoned that stimuli‐responsive formation of the soft material lends itself to nanotechnology applications such as controlled release or scavenging of targeted compounds. Filling the basket: Photoinduced decarboxylation of molecular baskets functionalized with glutamic acids was found to, in water, give amphiphilic cavitands. These cavitands assemble into organic nanoparticles that could be used for scavenging toxic molecules, promoting chemical reactions or delivering drugs. [ABSTRACT FROM AUTHOR]