Electron density-based GPT for optimization and suggestion of host–guest binders

Here we present a machine learning model trained on electron density for the production of host–guest binders. These are read out as simplified molecular-input line-entry system (SMILES) format with >98% accuracy, enabling a complete characterization of the molecules in two dimensions. Our model generates three-dimensional representations of the electron density and electrostatic potentials of host–guest systems using a variational autoencoder, and then utilizes these representations to optimize the generation of guests via gradient descent. Finally the guests are converted to SMILES using a transformer. The successful practical application of our model to established molecular host systems, cucurbit[n]uril and metal–organic cages, resulted in the discovery of 9 previously validated guests for CB[6] and 7 unreported guests (with association constant Ka ranging from 13.5 M−1 to 5,470 M−1) and the discovery of 4 unreported guests for [Pd214]4+ (with Ka ranging from 44 M−1 to 529 M−1)

Triple Self-Sorting in Constitutional Dynamic Networks: Parallel Generation of Cu(I), Fe(II) and Zn(II) Imine-Based Metal Complexes

Three imine-based metal complexes, having no overlap in terms of their compositions, have been simultaneously generated from the self-sorting of a constitutional dynamic library (CDL) containing three amines, three aldehydes and three metal salts. The hierarchical ordering of the stability of three metal complexes assembled and the leveraging of the antagonistic and agonistic relationships existing between the constituents within the constitutional dynamic network corresponding to the CDL were pivotal in achieving the desired sorting. The mechanism and the driving forces underlying the self-sorting process have been studied by NMR. The self-sorting of the Fe(II) and Zn(II) complexes was found to depend on an interplay between the thermodynamic driving forces and a kinetic trap involved in their assembling. These results also exemplify the concept of “simplexity” –the fact that the output of a self-assembling system may be simplified by increasing its initial compositional complexity—as the two complexes could self-sort only in the presence of the third pair of organic components, those of the Cu(I) complex.<br /

Simultaneous Generation of a [2×2] Grid-like Complex and a Linear Double Helicate: A Three-Level Self-Sorting Process

Two constitutional dynamic libraries (CDLs)—each containing two amines, two dialdehydes and two metal salts—have been found to self-sort, generating two pairs of imine-based metallosupramolecular architectures sharing no component, a [2×2] grid-like complex and a linear double helicate. These CDLs provided unique examples of a three-level self-sorting process, as only two imine-based ligand constituents, two metal complexes and two architectures were selected during their assembling out of all the possible combinations of their initial components. The metallosupramolecular architectures assembled were characterized by NMR, mass spectroscopy, and X-ray crystallography.</div

Dissipative self-assembly of metal-organic complexes

Implementing dissipative processes in networks of dynamic molecules holds great promise for developing new functional behaviours. Here we report the use of trichloroacetic acid as a chemical fuel to temporarily push networks of dynamic imine-based metal complexes far from thermodynamic equilibrium, forcing them to express high free-energy complexes otherwise unfavourable under equilibrium conditions. Basic design principles were determined for the creation of such networks. Where a complex distribution of products was obtained at equilibrium, the fuel-induced rearrangement temporarily yielded a simplified output, forcing a more structured high-energy distribution of products. Where a single complex was obtained at equilibrium, the fuel-induced rearrangement temporarily modified the properties of this complex. By doing so, the mechanical properties of an helical macrocyclic complex could be temporarily altered by rearranging it into a [2]catenane

The self-sorting behavior of circular helicates and molecular knots and links

We report on multicomponent self-sorting to form open circular helicates of different sizes from a primary monoamine, Fe ions, and dialdehyde ligand strands that differ in length and structure by only two oxygen atoms. The corresponding closed circular helicates that are formed from a diamine-a molecular Solomon link and a pentafoil knot-also self-sort, but up to two of the Solomon-link-forming ligand strands can be accommodated within the pentafoil knot structure and are either incorporated or omitted depending on the stage that the components are mixed. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Lanthanide template synthesis of a molecular trefoil knot

Molecular knots1 and entanglements are featured in cyclic DNA2 and some proteins3 and are thought to play an important role in the chemical and physical properties of both natural and synthetic polymers.4 Sauvage and co-workers prepared the first synthetic molecular trefoil knot by connecting the end-groups of a linear two-metal-ion double helicate.5 However, the earliest published idea for a template synthesis of a trefoil knot is Sokolov’s proposal6 for assembling three ligands around a metal center to generate the three crossings necessary7 in the cyclized product. Several groups have attempted to prepare trefoil knots using this strategy thus far without achieving the ultimate goal,8 although Hunter has succeeded in synthesizing a trefoil knot by folding a single ligand strand around a transition metal ion,9 and Siegel has made a ‘trefoil knotted cyclophane’ 10 using a related triskelion approach featuring a covalently bonded scaffold.1