Cavity Characterization in Supramolecular Cages.

Confining molecular guests within artificial hosts has provided a major driving force in the rational design of supramolecular cages with tailored properties. Over the last 30 years, a set of design strategies have been developed that enabled the controlled synthesis of a myriad of cages. Recently, there has been a growing interest in involving in silico methods in this toolbox. Cavity shape and size are important parameters that can be easily accessed by inexpensive geometric algorithms. Although these algorithms are well developed for the detection of nonartificial cavities (e.g., enzymes), they are not routinely used for the rational design of supramolecular cages. In order to test the capabilities of this tool, we have evaluated the performance and characteristics of seven different cavity characterization software in the context of 22 analogues of well-known supramolecular cages. Among the tested software, KVFinder project and Fpocket proved to be the most software to characterize supramolecular cavities. With the results of this work, we aim to popularize this underused technique within the supramolecular community.

Ligand-enabled oxidation of gold(i) complexes with o-quinones.

Chelating P^P and hemilabile P^N ligands were found to trigger the oxidation of Au(i) complexes by o-benzoquinones. The ensuing Au(iii) catecholate complexes have been characterized by NMR spectroscopy, single crystal X-ray diffraction and X-ray absorption spectroscopy. They adopt tetracoordinate square-planar structures. Reactivity studies substantiate the reversibility of the transformation. In particular, the addition of competing ligands such as chloride and alkenes gives back Au(i) complexes with concomitant release of the o-quinone. DFT calculations provide insight about the structure and relative stability of the Au(i) o-quinone and Au(iii) catecholate forms, and shed light on the 2-electron transfer from gold to the o-quinone.

Cu-Catalyzed P-C bond formation/cleavage: straightforward synthesis/ring-expansion of strained cyclic phosphoniums.

Upon reaction with copper(i), peri-halo naphthyl phosphines readily form peri-bridged naphthyl phosphonium salts. The reaction works with alkyl, aryl and amino substituents at phosphorus, with iodine, bromine and chlorine as a halogen. It proceeds under mild conditions and is quantitative, despite the strain associated with the resulting 4-membered ring structure and the naphthalene framework. The transformation is amenable to catalysis. Under optimized conditions, the peri-iodo naphthyl phosphine 1-I is converted into the corresponding peri-bridged naphthyl phosphonium salt 2b in only 5 minutes at room temperature using 1 mol% of CuI. Based on DFT calculations, the reaction is proposed to involve a Cu(i)/Cu(iii) cycle made of P-coordination, C-X oxidative addition and P-C reductive elimination. This copper-catalyzed route gives a general and efficient access to peri-bridged naphthyl phosphonium salts for the first time. Reactivity studies could thus be initiated and the possibility to insert gold into the strained P-C bond was demonstrated. It leads to (P,C)-cyclometallated gold(iii) complexes. According to experimental observations and DFT calculations, two mechanistic pathways are operating: (i) direct oxidative addition of the strained P-C bond to gold,(ii) backward-formation of the peri-halo naphthyl phosphine (by C-P oxidative addition to copper followed by C-X reductive elimination), copper to gold exchange and oxidative addition of the C-X bond to gold. Detailed analysis of the reaction profiles computed theoretically gives more insight into the influence of the nature of the solvent and halogen atom, and provides rationale for the very different behaviour of copper and gold in this chemistry.

Gold(III) π-Allyl Complexes.

Gold(III) π-complexes have been authenticated recently with alkenes, alkynes, and arenes. The key importance of PdII π-allyl complexes in organometallic chemistry (Tsuji-Trost reaction) prompted us to explore gold(III) π-allyl complexes, which have remained elusive so far. The (P,C)AuIII (allyl) and (methallyl) complexes 3 and 3' were readily prepared and isolated as thermally and air-stable solids. Spectroscopic and crystallographic analyses combined with detailed DFT calculations support tight quasi-symmetric η3 -coordination of the allyl moiety. The π-allyl gold(III) complexes are activated towards nucleophilic additions, as substantiated with ß-diketo enolates.

Indolino-Oxazolidine Acido- and Photochromic System Investigated by NMR and Density Functional Theory Calculations.

Three addressable indolino-oxazolidine units connected through an isomerizable double bond to a substituted thiophene represent a smart example of a multiaddressable system whose reversible responses could be selectively activated on demand. Experimental and theoretical approaches to push forward the understanding of the system mechanism and set pathways to design optimized compounds for suitable application are here presented. NMR and UV-visible spectroscopies are used for structural and kinetic studies, while density functional theory (DFT) calculations pave the way to highlight energetic and electronic processes that are involved. Substitution and solvent effects toward the reactivity of the compounds are experimentally studied and combined with theoretical calculations. The most efficient and selective stimuli to travel between the four possible states resulting from the ring-opening of indolino[2,1- b]oxazolidine (generally referenced as BOX) derivatives and the trans-cis isomerization of the ethylenic junction are elucidated.

Redox-Driven Transformation of a Discrete Molecular Cage into an Infinite 3D Coordination Polymer.

Two M12 L6 redox-active self-assembled cages constructed from an electron-rich ligand based on the extended tetrathiafulvalene framework (exTTF) and metal complexes with a linear geometry (PdII and AgI ) are depicted. Remarkably, based on a combination of specific structural and electronic features, the polycationic self-assembled AgI coordination cage undergoes a supramolecular transformation upon oxidation into a three-dimensional coordination polymer, that is characterized by X-ray crystallography. This redox-controlled change of the molecular organization results from the drastic conformational modifications accompanying oxidation of the exTTF moiety.

Controlling the Host-Guest Interaction Mode through a Redox Stimulus.

A proof-of-concept related to the redox-control of the binding/releasing process in a host-guest system is achieved by designing a neutral and robust Pt-based redox-active metallacage involving two extended-tetrathiafulvalene (exTTF) ligands. When neutral, the cage is able to bind a planar polyaromatic guest (coronene). Remarkably, the chemical or electrochemical oxidation of the host-guest complex leads to the reversible expulsion of the guest outside the cavity, which is assigned to a drastic change of the host-guest interaction mode, illustrating the key role of counteranions along the exchange process. The reversible process is supported by various experimental data (1 H NMR spectroscopy, ESI-FTICR, and spectroelectrochemistry) as well as by in-depth theoretical calculations performed at the density functional theory (DFT) level.

Reversible C60 Ejection from a Metallocage through the Redox-Dependent Binding of a Competitive Guest.

The reversible encapsulation of a tetrapyridyl extended-tetrathiafulvalene (exTTF)-based ligand (m-Py)exTTF by a tetragonal Zn-porphyrin-based prismatic nanocage (1) is described. The reversible uptake and release of the (m-Py)exTTF guest proceeds through drastic electronic and conformational changes occurring upon oxidation of the latter. This reversible system has been explored in a guest-exchange process, by addition of (m-Py)exTTF to the host-guest complex [C60 ⊂1], leading to fullerene C60 ejection from the host cavity. Remarkably, the subsequent redox-triggered ejection of (m-Py)exTTF, leads to the recovery of the empty cage 1, which remains available for further C60 encapsulation. The C60 ejection is justified by the preferable coordination of the pyridine anchors of (m-Py)exTTF to the two Zn-porphyrin units of 1. This approach, based on the use of a switchable competitive guest, offers a promising new strategy for guest-delivery control.

Neutral versus polycationic coordination cages: a comparison regarding neutral guest inclusion.

A neutral self-assembled container synthesized from a concave π-extended tetrathiafulvalene (exTTF) ligand and the cis-Pd(dctfb)2(cod) complex (dctfb = 3,5-dichloro-2,4,6-trifluorobenzene; cod = 1,5-cyclooctadiene) is described. This molecular host exhibits a good binding ability for fused polyaromatic substrates. The corresponding inclusion properties are compared with those of a previously described analogous octacationic cage, offering therefore the opportunity to address the effect of the cavity charge state over the binding of neutral molecules.

Reversible Guest Uptake/Release by Redox-Controlled Assembly/Disassembly of a Coordination Cage.

Controlling the guest expulsion process from a receptor is of critical importance in various fields. Several coordination cages have been recently designed for this purpose, based on various types of stimuli to induce the guest release. Herein, we report the first example of a redox-triggered process from a coordination cage. The latter integrates a cavity, the panels of which are based on the extended tetrathiafulvalene unit (exTTF). The unique combination of electronic and conformational features of this framework (i.e. high π-donating properties and drastic conformational changes upon oxidation) allows the reversible disassembly/reassembly of the redox-active cavity upon chemical oxidation/reduction, respectively. This cage is able to bind the three-dimensional B12 F12 (2-) anion in a 1:2 host/guest stoichiometry. The reversible redox-triggered disassembly of the cage could also be demonstrated in the case of the host-guest complex, offering a new option for guest-delivering control.

Huge electro-/photo-/acidoinduced second-order nonlinear contrasts from multiaddressable indolinooxazolodine.

In this work, linear and nonlinear optical properties of electro-/acido-/photoswitchable indolino[2,1-b]oxazolidine derivatives were investigated. The linear optical properties of the closed and open forms have been characterized by UV-visible and IR spectroscopies associated with DFT calculations. Nonlinear optical properties of the compounds have been obtained by ex situ and in situ hyper-Rayleigh experiments in solution. We show that protonated, oxidized, and irradiated open forms exhibit the same visible absorption and NLO features. In particular, the closed and open forms exhibit a huge contrast of the first hyperpolarizability with an enhancement factor of 40-45. Additionally, we have designed an original electrochemical cell that allows to monitor in situ the hyper-Rayleigh response upon electrical stimulus. We report notably a partial but good and reversible NLO contrast in situ during oxidation/reduction cycles. Thereby, indolinooxazolidine moieties are versatile trimodal switchable units which are very promising for applications in devices.

Silica-mediated synthesis of indolinooxazolidine-based molecular switches.

A novel and convenient method for the synthesis of photochromic compounds is reported here. It is based on the use of commercially available untreated silica, as an efficient catalyst to perform the condensation between indolinooxazolidine derivatives and aromatic aldehydes under solvent-free conditions. The scope and limitations of this transformation were investigated and several novel photochromic indolinooxazolidines were synthesized. This methodology can also be applied to the synthesis of other photoactive compounds such as spiropyrans or spirooxazines. According to our working protocol the reaction did not require any solvent or additional reagents and gave the products within 10 min in isolated yields of up to 90%.

Indolinooxazolidine: a versatile switchable unit.

The design of multiresponsive systems continues to arouse a lot of interest. In such multistate/multifunctional systems, it is possible to isomerize a molecular system from one metastable state to another by application of different stimulation such as light, heat, proton, or electron. In this context, some researches deal with the design of multimode switch where a same interconversion between two states could be induced by using indifferently two or more different kind of stimuli. Herein, we demonstrate that the association of an indolinooxazolidine moiety with a bithiophene unit allows the development of a new trimode switch. A reversible conversion between a colorless closed form and a colorful open form can be equally performed by light, proton, or electrical stimulation. In addition, the oxidation of this system allows the generation of a third metastable state.

Design and synthesis of 21-alkynylaryl pregnenolone derivatives and evaluation of their anticancer activity.

A series of novel C21-alkynylaryl derivatives of pregnenolone were synthesized and screened for anticancer activity against a panel of seven human cancer cell lines (LNCaP, A549, MCF7, HeLa, A431, HepG2, HT29). The data revealed that these compounds can be potential antitumour agents against the specific cell models. Compound 6f bearing a 2-trifluoromethylphenyl group displayed improved cytotoxicity towards all cancer cell lines used. A431 cells were the most sensitive with derivatives 6e-6h bearing electron withdrawing substituents exhibiting high potency with IC50 values ranging between 2.18 and 0.54µM and drastic inhibition of the prosurvival PI3K-Akt/PKB pathway.

A simple molecule-based octastate switch.

Dithienylethene oxazolidine hybrid system connected through an isomerizable double bond exists under eight molecular states on demand. Combinations of electrocyclization of dithienylethene, Z/E isomerization and acid-base oxazolidine change cause selective addressabilities. Two intricate gated photochromic performances allow the execution of an 8-step molecular switch, which renders this molecular system the most complex known up to date.

Synthesis of symmetrical and nonsymmetrical bisthienylcyclopentenes.

Diarylethenes possess unique structural properties, which enabled them to find widespread applications in the field of photochromism. Nowadays, bisthienylcyclopentenes (BTCs) present the most popular subfamily of these compounds, which are widely used as P-type chromophores. This minireview summarises the main strategies for the synthesis of symmetrical and nonsymmetrical BTCs. In addition, attention is drawn to desymmetrisations achieved by monosubstitutions, which is not frequently utilised, although it can be highly advantageous. This is supported with some of the authors' latest results.