Solvation rules: aromatic interactions outcompete cation-π interactions in synthetic host-guest complexes in water.

Chemical double mutant cycles were used to measure the interaction of a -methyl pyridinium cation with a π-box in a calix[4]pyrrole receptor. Although the cation-π interaction is attractive (-11 kJ mol), it is 7 kJ mol less favourable than the corresponding aromatic interaction with the isosteric but uncharged tolyl group.

Aromatic interactions with heterocycles in water.

Conformationally well-defined supramolecular complexes that can be studied in different solvents provide a platform for separating and quantifying free energy contributions due to functional group interactions and desolvation. Here 1:1 complexes formed between four different calix[4]pyrrole receptors and eleven different pyridine -oxide guests have been used to dissect the factors that govern aromatic interactions with heterocycles in water and in chloroform solution. H NMR spectroscopy shows that the three-dimensional structures of the complexes are fixed by four H-bonding interactions between the pyrrole donors at the bottom of the receptor and the -oxide acceptor on the guest, locking the geometrical arrangement of interacting functional groups in the binding pocket at the other end of the receptor.

Substituent effects on aromatic interactions in water.

Molecular recognition in water involves contributions due to polar functional group interactions, partial desolvation of polar and non-polar surfaces and changes in conformational flexibility, presenting a challenge for rational design and interpretation of supramolecular behaviour. Conformationally well-defined supramolecular complexes that can be studied in both water and non-polar solvents provide a platform for disentangling these contributions. Here 1 : 1 complexes formed between four different calix[4]pyrrole receptors and thirteen different pyridine -oxide guests have been used to dissect the factors that govern substituent effects on aromatic interactions in water.

What has achieved in its first few years?

It has been a pleasure and a privilege to serve as the first Editor-in-Chief of for the past 6 years. I step down at the end of December 2021, having completed two 3-year terms, and am taking the opportunity here to reflect on some of the successes and challenges that the journal has experienced and the innovations that we have introduced. When I was first approached back in 2015, the breadth of the journal, covering the whole of science, resonated with my own interests: my research career has ranged across the entire landscape of chemistry, while my leadership roles have embraced all of science, technology and medicine.

Using Solid Catalysts in Disulfide-Based Dynamic Combinatorial Solution- and Mechanochemistry.

It was shown for the first time that solid amines can act as catalysts for disulfide-based dynamic combinatorial chemistry (DCC) by ball mill grinding. The mechanochemical equilibrium for the two disulfide reactions studied was reached within 1-3 h using ten different amine catalysts. This contrasts with the weeks to months to achieve solution equilibrium for most solid amine catalysts at 2 %mol mol concentration in a 2 mMolar disulfide dynamic combinatorial library in a suitable solvent.

Changing the game of time resolved X-ray diffraction on the mechanochemistry playground by downsizing.

Time resolved in situ (TRIS) monitoring has revolutionised the study of mechanochemical transformations but has been limited by available data quality. Here we report how a combination of miniaturised grinding jars together with innovations in X-ray powder diffraction data collection and state-of-the-art analysis strategies transform the power of TRIS synchrotron mechanochemical experiments. Accurate phase compositions, comparable to those obtained by ex situ measurements, can be obtained with small sample loadings.

Understanding the unexpected effect of frequency on the kinetics of a covalent reaction under ball-milling conditions.

We here explore how ball-mill-grinding frequency affects the kinetics of a disulfide exchange reaction. Our kinetic data show that the reaction progress is similar at all the frequencies studied (15-30 Hz), including a significant induction time before the nucleation and growth process starts. This indicates that to start the reaction an initial energy accumulation is necessary.

Understanding the Influence of Surface Solvation and Structure on Polymorph Stability: A Combined Mechanochemical and Theoretical Approach.

We explore the effect of solvent concentration on the thermodynamic stability of two polymorphs of a 1:1 cocrystal of theophylline and benzamide subjected to ball-mill liquid assisted grinding (LAG) and we investigate how this can be related to surface solvent solvation phenomena. In this system, most stable bulk polymorph form II converts to metastable bulk polymorph form I upon neat grinding (NG), while form I can fully or partially transform into form II under LAG conditions, depending on the amount of solvent used. Careful and strict experimental procedures were designed to achieve polymorph equilibrium under ball-mill LAG conditions for 16 different solvents.

Editorial for 'New talent' collection: introducing New Talent in chemistry and material science.

We introduce 14 articles published as part of the 'New talent' special collection of invited articles to showcase some of the exciting work being funded by the Royal Society. As Royal Society University Research Fellows or Dorothy Hodgkin Fellowship holders, the contributors to this collection are rising stars in their areas of research. This collection also illustrates the close collaboration between and the Royal Society of Chemistry.

Reliable Mechanochemistry: Protocols for Reproducible Outcomes of Neat and Liquid Assisted Ball-mill Grinding Experiments.

The equilibrium outcomes of ball mill grinding can dramatically change as a function of even tiny variations in the experimental conditions such as the presence of very small amounts of added solvent. To reproducibly and accurately capture this sensitivity, the experimentalist needs to carefully consider every single factor that can affect the ball mill grinding reaction under investigation, from ensuring the grinding jars are clean and dry before use, to accurately adding the stoichiometry of the starting materials, to validating that the delivery of solvent volume is accurate, to ensuring that the interaction between the solvent and the powder is well understood and, if necessary, a specific soaking time is added to the procedure. Preliminary kinetic studies are essential to determine the necessary milling time to achieve equilibrium.

Selective C encapsulation by a robust octameric nanospheroid held together by 48 cooperative hydrogen bonds.

Self-assembly of multiple building blocks via hydrogen bonds into well-defined nanoconstructs with selective binding function remains one of the foremost challenges in supramolecular chemistry. Here, we report the discovery of a enantiopure nanocapsule that is formed through the self-assembly of eight amino acid functionalised molecules in nonpolar solvents through 48 hydrogen bonds. The nanocapsule is remarkably robust, being stable at low and high temperatures, and in the presence of base, presumably due to the co-operative geometry of the hydrogen bonding motif.

Catenation and encapsulation induce distinct reconstitutions within a dynamic library of mixed-ligand ZnL cages.

Two new ZnL cages composed of diamine subcomponents containing either naphthalene diimide (NDI) or porphyrin moieties are described. Their structural differences allow these cages to exhibit distinct interactions with different chemical stimuli, yielding different supramolecular products. The electron-poor NDI subunits of the first cage were observed to thread through electron-rich aromatic crown-ether macrocycles, forming mechanically-interlocked species up to a [3]catenane, whereas the porphyrin ligands of the second cage interacted favourably with C, causing it to be bound as a guest.

Guest-induced transformation of a porphyrin-edged Fe(II)4L6 capsule into a Cu(I)Fe(II)2L4 fullerene receptor.

The combination of a bent diamino(nickel(II) porphyrin) with 2-formylpyridine and Fe(II) yielded an Fe(II) 4 L6 cage. Upon treatment with the fullerenes C60 or C70 , this cage was found to transform into a new host-guest complex incorporating three Fe(II) centers and four porphyrin ligands, in an arrangement that is hypothesized to maximize π interactions between the porphyrin units of the host and the fullerene guest bound within its central cavity. The new complex shows coordinative unsaturation at one of the Fe(II) centers as the result of the incommensurate metal-to-ligand ratio, which enabled the preparation of a heterometallic cone-shaped Cu(I) Fe(II) 2 L4 adduct of C60 or C70 .

Molecular motion of donor-acceptor catenanes in water.

In this article, we use (1)H NMR spectroscopy to study the spontaneous molecular motion of donor-acceptor [2]catenanes in water. Our data supports the hypothesis that conformational motion dominantly occurs through a pirouetting mechanism, which involves less exposure of hydrophobic surfaces than in a rotation mechanism. Motion is controlled by the size of the catenane rings and the arrangement of the electron-deficient and electron-rich aromatic units.

Direct observation of intermediates in a thermodynamically controlled solid-state dynamic covalent reaction.

We present the first polymorph interconversion study that uses solid-state dynamic covalent chemistry (DCC). This system exhibits unexpected and rich behavior, including the observation that under appropriate conditions the polymorph interconversion of a heterodimer proceeds through reversible covalent chemistry intermediates, and this route is facilitated by one of the two disulfide homodimers involved in the reaction. Furthermore, we demonstrate experimentally that in all cases a dynamic equilibrium is reached, meaning that changing the milling conditions affects the free energy difference between the two polymorphs and thus their relative stability.

Homochiral and meso figure eight knots and a Solomon link.

A homochiral naphthalenediimide-based building block forms in water a disulfide library of macrocycles containing topological isomers. We attempted to identify each of these isomers, and explored the mechanisms leading to their formation. The two most abundant species of the library were assigned as a topologically chiral Solomon link (60% of the library, as measured by high-performance liquid chromatography (HPLC)) and a topologically achiral figure eight knot (18% by HPLC), competing products with formally different geometries but remarkably similar 4-fold symmetries.

Disulfide exchange: exposing supramolecular reactivity through dynamic covalent chemistry.

A Tutorial Review of the subtle supramolecular interactions influencing the outcomes of equilibrating systems, focusing on the dynamic covalent chemistry (DCC) of disulfide exchange reactions, is presented. We discuss the topics of cation-π interactions (2.1), hydrophobic effects (2.