Virtual Conference on Molecular Capsules: from Design to Application

Invited Speakers:

25 minute presentations by each speaker, followed by 5 minutes of questions

ABSTRACTS

 Joost Reek

University of Amsterdam

Transition Metal Catalysis in Confined Spaces

The interface between supramolecular chemistry and transition metal catalysis has received surprisingly little attention in contrast to the individual disciplines. It provides, however, novel and elegant strategies that lead to new tools for the search of effective catalysts, and as such this has been an important research theme in our laboratories. In this presentation I will focus on supramolecular strategies to put transition meta catalysts in confined spaces, thereby controlling crucial properties as activity, selectivity and stability. As the strategy is fundamentally different from the traditional ligand approach, unusual properties can be achieved. More recently, we also explored the use of large nanospheres that have the size of small peptides. With these cages we perform catalysis at high local concentration of the components, just like in enzymes, leading to rate acceleration for several different reactions. These nanospheres can also be used for electrochemical events and as such for proton reduction and water oxidation catalysis, and those decorated with peptides are perfect enzyme mimics.

 

Amnon Bar Shir

Weizmann Institute of Science

Guest Exchange Saturation Transfer (GEST): Quantifying Exchange in Host-Guest Systems and Applying to Molecular MR Imaging

Dynamic processes in host–guest systems, such as the exchange between bound and free guests, can endow such systems with unique properties and function. However, both the dynamic exchange and the relatively low concentration of a studied complex reduce the sensitivity and limit the efficiency of the currently available analytical tools to explore such processes. Here, we present an NMR approach based on saturation transfer, termed GEST – Guest Exchange Saturation Transfer. This technique can be used to detect micromolar concentrations of complexes with the sensitivity of millimolar concentrations, thus offering the ability to amplify otherwise undetected signals in NMR spectra. In addition, by performing the GEST experiment and fitting the data using computational simulations, the exchange rate of free and bound guest and the fractional occupancy of the host can be extracted. We further present several examples of how GEST can be employed to extract important information from host–guest systems. This method can expand the NMR toolbox available to study dynamic host–guest systems in solution without any special expertise or dedicated hardware and can assist in developing more advanced host–guest systems that can be used for many applications, including in molecular and cellular MRI. Specific examples of the use of 19F-GEST to study systems composed of octa-acid, cucurbit[n]urils, bambusurils, and cyclodextrins are discussed.

 

Giovanni Pavan

Department of Appliced Science and Technology, Politecnico di Torino, Turin, Italy & Department of Innovative Technologies, University of Applied Sciences ad Arts of Southern Switzerland, Lugano, Switzerland

Learning How to Control Azobenzene Isomerizazion in Confined Volumes and Supramolecular Cavities by Using Molecular Models

Azobenzene is a well-known light-responsive compound, widely used for its photoswitchable behavior. This can be efficiently and reversibly switched between trans and cis isomers upon exposure to light irradiation, which made of azobenzene derivatives key ingredients for the development of light-powered molecular machines and active materials. While the isomerization of azobenzene free in solution is fast and efficient, it is has been shown that this can be slowed down or even impeded under confinement or in crowded environments such as, for example, inside ordered assemblies or inside supramolecular cages. Obtaining useful molecular informations on how to control the rate/efficiency of azobenzene isomerization by rationally controlling its confinement would be extremely interesting, but at the same time this also difficult. Molecular simulations can help to achieve this goal. Recently, we combined multiscale molecular modeling and advanced simulation methods to study the isomerization of azobenzene inside selfassembled tubes, filaments and in the cavity of supramolecular cages. Our computational approaches allowed to characterize the mechanism and kinetics of azobenzene isomerization in the confined environments, highlighting the relationship between the isomerization rate/efficiency and the volume of the cavities. This opens new possibilities, where multiscale models can be used to learn how to rationally design porous supramolecular structures where isomerization events occur with tunable kinetics as confined in their internal cavities, or of self-assembled materials that can react in a controllable dynamic way to light stimuli.

 

Anna McConnell

Otto Diels Institute of Organic Chemistry, Kiel University

 Paramagnetic NMR Spectroscopy for the Characterisation of Metal-Organic Cages

NMR spectroscopy is an invaluable tool for the structural characterisation of metal-organic cages in solution but its application to the characterisation of paramagnetic cages has a number of challenges; the paramagnetic centres shorten the relaxation times so that structural information in the form of J-coupling is not observable due to broad linewidths and signal loss during acquisition from relaxation makes many standard pulse programs unsuitable. We present a toolbox of paramagnetic NMR methods for the characterisation of paramagnetic cages complementary to the standard suite of NMR methods for diamagnetic compounds.

 

Carmelo Sgarlata

University of Catania, Italy

Solution Thermodynamics of Guest-Templated Capsules and Aggregates

Weak, non-covalent interactions are key tools employed in supramolecular chemistry to handle molecular recognition and self-assembly processes for the design and synthesis of novel structures such as molecular capsules, cages, flasks and containers. By mimicking the active sites and pockets of enzymes, capsular assemblies are able to isolate suitable guest molecules from the surrounding media and promote chemical reactions in a controlled fashion. Supramolecular chemistry is conveniently moving towards the aqueous domain in order to involve biochemistry or stimulate new paths in green chemistry related areas. The dramatic differences between the bulk water and the inner space within a molecular container provide the thermodynamic drive to guest complexation which, in this peculiar solvent, cannot be induced only by structural complementarity/fitting between host and guest. Consequently, the determination of thermodynamic parameters and forces driving molecular recognition processes and/or the formation of self-assembled capsular entities in water is a crucial step for the rational design of efficient supramolecular containers. Our recent work on the molecular recognition of charged guests by clusters, calixarene receptors bearing sulphonato or ammonium functionalities as well as on the formation of anion-templated capsules and compartments or host-guest based supra-amphiphiles and aggregates in aqueous solution will be presented. A combination of different techniques, such as NMR, UV-vis and isothermal titration calorimetry (ITC) allowed for the deconvolution of the host-guest equilibria and the determination of the species forming in solution. In particular, ITC data allowed for splitting the Gibbs free energy term into the ΔH° and ΔS° components thus unveiling the driving forces for both guest recognition and self-assembly phenomena. Results suggest new strategies towards the construction of guest-templated molecular containers which may be employed as nano-shuttles for drug-delivery or reaction nano-chambers in highly competitive media like water.

 

Stuart James

Queen’s University Belfast

Porous Liquids - a new playing ground for molecular hosts

Porosity is a fundamentally important property of materials that leads to a number of applications. It is normally only associated with the solid state. However, recently we showed that through careful design of the components, porous liquids can be prepared.[1-3] Porous Liquids (PLs) are liquids that contain permanent, well-defined, empty cavities of molecular dimensions. Unlike conventional solvents, they are able to dissolve very large amounts of gas in a size- and shape-selective manner. This talk will focus on the synthesis of porous liquids from molecular cages including the various design considerations and will tell the story of our various efforts over the years that led up to the examples we have published. If time permits some of our most recent work on diversifying and engineering porous liquids towards applications will be included.[4]

N. O’Reilly et al. Chem. Eur. J. 2007, 13, 3020.

Melaugh et al. PCCP, 2014, 16, 9422.

N. Giri et al. Nature, 2015, 527, 216.

 Jeanne Bolliger

Oklahoma State University

Coordination Cages: Host Guest Chemistry and Applications in Supramolecular Catalysis

Solvent-dependent host-guest chemistry, favoring of otherwise disfavored conformations of large guests, and catalytic degradation of the insecticide dichlorvos has been achieved with self-assembled coordination cages. A water-soluble tetrahedral Fe4L6 capsule was shown to self-assemble enantioselectively from an enantiopure diamine and 2-formylpyridine in the presence of an iron(II) salt. These versatile water-soluble capsules are capable of binding a wide range of organic guests in their large hydrophobic cavities. Among these guests is the neurotoxic insecticide dichlorvos, for which the coordination capsule serves as a competent supramolecular catalyst for its hydrolysis. A self-assembled face-capped tetrahedral Fe4L4 coordination cage: Depending on the counter ion, this face-capped tetrahedral capsule is either soluble in water or in organic solvents and shows a solvent-dependent preference for encapsulation of certain classes of guest molecules. Due to the flexible subcomponents, this Fe4L4 cage is capable of adapting its shape to the encapsulated guest, thereby ensuring strong binding of both small and large guests. Upon encapsulation, large symmetric guest molecules show significantly lower symmetry and adopt conformations which are not thermodynamically favored in their free state. In addition, restricted motion about single bonds leads to diastereotopic protons on CH2 groups of encapsulated guests.

 

Jack Clegg

University of Queensland

Untangling the [M2L3] ↔ [M4L6] Equilibrium: Using Sterics to Control Cage Geometry

We have prepared a series of phenyl-spaced quaterpridine ligands with a varying degrees of steric bulk situated on the ligand core. The self-assmebly of these ligands with first-row transition metals to form metallo-supramolecular tetrahedra has also been performed. Depending on the identity of the metal and bulky substitutent employed, the [M2L3] helicate ↔ [M4L6] tetrahedron equilibrium sits in different places, ranging from pure helicate to pure tetrahedron. Employing comparatively inert metal-ions has allowed for the kinetics and mechanism of helicate ↔ tetrahedron interconversion to be established.

 

Mike Ward

University of Warwick

Chemical Catalytic Properties and Photophysical Properties of a Coordination Cage Host

An octanuclear cubic coordination cage host has been investigated for (i) its ability to catalyse reactions of bound substrates; and (ii) to effect photoinduced energy- or electron-transfer from the array of chromophores in the cage superstructure to bound guests. Chemical catalysis is based on the ability of the cationic (16+) cage to accumulate anions around its surface which brings them into close proximity to hydrophobic guests which bind in the central cavity in water. Several different substrates undergo reactions promoted by hydroxide ions including an E2 elimination reaction (Kemp elimination), phosphotriester hydrolysis, nucleophilic attack on dinitrofluorobenzene, and an aldol condensation of indane-dione. Whilst some of the catalysed reactions are associated with strong binding of the substrate in the cage cavity, in other cases blocking the cavity with an inert inhibitor makes no difference to catalysis which we believe to be associated with the exterior surface of the cage. In addition isostructural examples of this cage type can be prepared containing photophysically-active units in the cage: these are either phosphorescent Os(II) complex units at the cage vertices, or fluorescent naphthyl units incorporated into the ligands. Bound guests are therefore surrounded by a large number of chromophores in close proximity, and in several cases we have observed fast photoinduced electron transfer to the guests generating short-lived charge-separated states (host radical cation, guest radical anion) as a precursor to possible photo-redox catalysis in the cage cavity.

 

Jonathan Nitschke

University of Cambridge

Many Forms and Functions of Coordination Cages

Dipolar, quadrupolar, and steric effects can be combined with metal coordination and templation to generate higher-order structures that incorporate different structural subunits. This talk will describe the design and uses of some of these three-dimensional architectures, as well as the means by which different subunits may communicate stereochemically with each other.

 

Paul Lusby

University of Edinburgh

New Opportunities in Capsule Catalysis

Substrate pre-​organization remains the paradigm for bio-​inspired catalytic strategies using supramol. capsule systems. This method has revealed limitations, most obviously product inhibition. We have recently developed an alternative approach that maximizes interactions between the substrate and the capsule's polar inner surface, thereby negating the need to rely on entropic effects. Initial results have shown highly efficient Diels-​Alder catalysis that combines activity comparable to catalytic antibodies with facile turnover. We will now show that this enthalpic approach to capsule catalysis is applicable to a broad scope of reactions. We will also describe how bulk-​phase catalysis can be triggered using the host-​guest induced release of highly reactive species.

 

Jacopo Tessarolo

TU Dortmund

Self-Assembly Strategies for Multifunctional and Stimuli-Responsive Coordination Cages

Metal-mediated self-assembly of supramolecular assemblies has been proven to be an efficient tool for developing new materials with well-defined shapes and geometries. Among this, banana-shaped bis-monodentate ligands react with Pd(II) cations to a broad range of topologies from small Pd2L4 cages, their interpenetrated dimers, rings of various size up to large Pd24L48 spheres. We embed functions into supramolecular cages, for example allosteric guest binding or light-responsive behaviour. However, most of the reported examples are highly symmetric structures carrying only one functionality. Previously we included two different functionalities, donor and acceptor moieties that undergo light-induced charge separation, within interpenetrated double cages. However, this system suffers from a lack of control over stoichiometry and stereochemistry. Recently we started to develop rational design strategies to assemble heteroleptic cages in a non-statistical fashion. We successfully used donor site engineering, geometric shape complementarity, and ring-embedded-metal approaches to obtain integrative self-sorting of multicomponent cages. Currently we are studying emerging properties based on the interactions of at least two functionalities.

 

Scott Cockroft

University of Edinburgh

Perturbing Equilibria: Nanopore Interrogation of Cage Complexes

Transmembrane nanopores provide a platform for sensing the dynamics of single molecules under perturbed and non-equilibrium conditions. This talk will outline how protein nanopores can be used for the enantiodiscrimination of metallosupramolecular complexes,[1] to observe the perturbing effects of applied electric fields on host-guest complexation,[2] and even to drive the nanomechanical chiral inversion of cage complexes.[3] Finally, the talk will outline methods for the synthetic modification of biological nanopores, which may pave the way for the development of membrane-spanning bio-synthetic supramolecular systems.[4][5] References: [1] J. A. Cooper, S. Borsley, P. J. Lusby, S. L. Cockroft, Chem. Sci., 8, 5005-09 (2017). [2] S. Borsley, J. A. Cooper, P. J. Lusby, S. L. Cockroft, Chem. Eur. J., 24, 4542 (2018). [3] S. Borsley, M. M. Haugland, S. Oldknow, J. A. Cooper, M. J. Burke, A. Scott, W. Grantham, J. Vallejo, E. K. Brechin, P. J. Lusby, S. L. Cockroft. Chem (Cell Press), 5, 1275-1292 (2019). [4] S. Borsley, S. L. Cockroft, ACS Nano, 12, 786 (2018). [5] M. M. Haugland, S. Borsley, D. F. Cairns-Gibson, A. Elmi, S. L. Cockroft. ACS Nano, 13, 4101 (2019).

 

Petr Kral

University of Illinois at Chicago

Atomistic Modeling of Nanoparticles Self-Assembling into Porous Superstructures

First, we discuss our modeling of nanoparticles (NPs) self-assembled into hollow clusters, with the goal to reveal their stabilization mechanisms. These hollow clusters have been observed to form by CdS NPs, depending on the pH of the solution. Our modeling reveals that local attractive interactions between the NPs ligands stabilize the clusters against repulsive Coulombic forces acting between the charged NPs. Next, we present our modeling of nanoflasks (cavities) formed by NPs with photo-switchable ligands. With the help of our modeling we can describe stabilization of poorly soluble molecules in these NPs cavities, as observed experimentally. We also show the chiral dependence of this stabilization and examine why the stabilized molecules have reaction rates different from bulk solutions. We also discuss modeling of other molecular carriers based on various types of micelles and functionalized NPs.