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We describe the preparation, dynamic, assembly characteristics of vase-shaped basket 1 3- 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 1 H Nuclear Magnetic Resonance (NMR), 1 H 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 [1 2 ] 6- , to be in equilibrium with monomers 1 (R) 3- (relaxed) and 1 (S) 3- (squeezed). Through simultaneous line-shape analysis of 1 H NMR data, kinetic and thermodynamic parameters characterizing these equilibria were quantified. Basket 1 (R) 3- includes anticancer drug mitoxantrone (MTO 2+ ) in its pocket to give stable binary complex [MTO⊂1] - (K d =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., (© 2023 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

We report Pd-catalyzed cyclotrimerization of (+)-α-bromoenone, obtained from monoterpene β-pinene, into an enantiopure cyclotrimer. This C 3 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., (© 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

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 Å 3 ) of 1 so that two equally sizeable compartments (190 Å 3 ) became joined through a conformationally flexible aromatic barrier. The compartments of such unique host could be populated with CCl 4 (88 Å 3 ; PC=46 %), CBr 4 (106 Å 3 ; 56 %) or their combination CCl 4 /CBr 4 (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., (© 2020 Wiley-VCH GmbH.)

In this work, we report a mechanism by which stereoisomeric and twisted capsules P/M-1 direct their dynamic chirality in the presence of haloalkane guests. The capsule comprises a static, but twisted, cage that is linked to a dynamic tris(2-pyridylmethyl)amine (TPA) lid at its top. From the results of experimental (NMR spectroscopy and X-ray crystallography) and computational (DFT) studies, the TPA lid was shown to assume clockwise (+) and counterclockwise (-) folds with diastereomeric (but racemic) capsules M-1(+) and M-1(-) interconverting at a rapid rate (ΔG ≠ 189K =9.1 kcal mol -1 ). The relative stability of the capsules was found to be a function of guest(s) residing in their interior (243/262 Å 3 ) with small CH 2 Cl 2 (61 Å 3 ) yielding roughly equal population of diastereomeric inclusion complexes. Larger guests, such as CCl 4 (89 Å 3 ) and CBr 4 (108 Å 3 ), however, formed M-1(-)⊂CX 4 at the expense of M-1(+)⊂CX 4 in circa 3:1 ratio. To account for the observation, theory (DFT:M06-2X/6-31+G*) and experiments ( 1 H NMR spectroscopy) were used to deduce that CX 4 guests become localized inside the twisted cage of the capsule by forming a C-X⋅⋅⋅π halogen bond [N c =d/(r H +r X )=0.91-0.92] with the benzene "floor" while encountering electrostatic repulsions with closer naphthalimide boundaries. At last, the TPA lid used its central methylene hydrogens to establish, within the M-1(-)⊂CX 4 , three stabilizing C-H⋅⋅⋅X-C interactions with the guest. The same C-H⋅⋅⋅X-C interactions, however, became weaker (or possibly vanished) after the conformational reorganization of the lid and the formation of less stable M-1(+)⊂CX 4 complex. On individual basis, C-H⋅⋅⋅X-C intermolecular contacts are weak and hardly detectable in the solution phase. In the case of capsule P/M-1, however, these contacts were multivalent and altogether strong enough to direct the host's dynamic chirality., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

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 1 6- , containing three glutamic acids at its rim. This concave compound is, in an aqueous environment (30 mm phosphate buffer at pH 7.0), monomeric ( 1 H NMR DOSY, DLS) with glutamic acid residues randomly oriented about its rim ( 1 H NMR and MM-OPLS3). The irradiation (300 nm) of 1 6- leads to the exclusive removal of its α-carboxylates to give amphiphilic 2 3- possessing γ-carboxylates. The photochemical transformation is a consecutive reaction with mono- and bis-decarboxylated products observed with 1 H NMR spectroscopy and ESI mass spectrometry. Amphiphilic 2 3- 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 1 6- into nanoparticulate 2 3- 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., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)