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We describe the preparation, dynamic, assembly characteristics of vase‐shaped basket 13− along with its ability to form an inclusion complex with anticancer drug mitoxantrone in abiotic and biotic systems. This novel cavitand has a deep nonpolar pocket consisting of three naphthalimide sides fused to a bicyclic platform at the bottom while carrying polar glycines at the top. The results of 1H Nuclear Magnetic Resonance (NMR), 1H NMR Chemical Exchange Saturation Transfer (CEST), Calorimetry, Hybrid Replica Exchange Molecular Dynamics (REMD), and Microcrystal Electron Diffraction (MicroED) measurements are in line with 1 forming dimer [12]6−, to be in equilibrium with monomers 1(R)3− (relaxed) and 1(S)3− (squeezed). Through simultaneous line‐shape analysis of 1H NMR data, kinetic and thermodynamic parameters characterizing these equilibria were quantified. Basket 1(R)3− includes anticancer drug mitoxantrone (MTO2+) in its pocket to give stable binary complex [MTO⊂1]− (Kd=2.1 μM) that can be precipitated in vitro with UV light or pH as stimuli. Both in vitro and in vivo studies showed that the basket is nontoxic, while at a higher proportion with respect to MTO it reduced its cytotoxicity in vitro. With well‐characterized internal dynamics and dimerization, the ability to include mitoxantrone, and biocompatibility, the stage is set to develop sequestering agents from deep‐cavity baskets. [ABSTRACT FROM AUTHOR]

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]

The precise positioning of functional groups about the inner space of abiotic hosts is a challenging task and of interest for developing more effective receptors and catalysts akin to those found in nature. To address it, we herein report a synthetic methodology for preparing basket‐like cavitands comprised of three different aromatics as side arms with orthogonal esters at the rim for further functionalization. First, enantioenriched A (borochloronorbornene), B (iodobromonorbornene), and C (boronorbornene) building blocks were obtained by stereoselective syntheses. Second, consecutive A‐to‐B and then AB‐to‐C Suzuki–Miyaura (SM) couplings were optimized to give enantioenriched ABC cavitand as the principal product. The robust synthetic protocol allowed us to prepare (a) an enantioenriched basket with three benzene sides and each holding either tBu, Et, or Me esters, (b) both enantiomers of a so‐called "spiral staircase" basket with benzene, naphthalene, and anthracene groups surrounding the inner space, and (c) a photo‐responsive basket bearing one anthracene and two benzene arms. [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]