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Relaying conformational change over several nanometers is central to the function of allosterically regulated proteins. Replicating this mechanism artificially would provide important communication tools, but requires nanometer-sized molecules that reversibly switch between defined shapes in response to signaling molecules. In this work, 1.8 nm long rigid rod oligo(phenylene-ethynylene)s are scaffolds for switchable multi-squaramide hydrogen-bond relays. Each relay can adopt either a parallel or an antiparallel orientation relative to the scaffold; the preferred orientation is dictated by a director group at one end. An amine director responded to proton signals, with acid-base cycles producing multiple reversible changes in relay orientation that were reported by a terminal NH, which is 1.8 nm distant. Moreover, a chemical fuel acted as a dissipative signal. As the fuel was consumed, the relay reverted to its original orientation, illustrating how information from out-of-equilibrium molecular signals can be communicated to a distant site.

Polyketides are a class of specialised metabolites synthesised by both eukaryotes and prokaryotes. These chemically and structurally diverse molecules are heavily used in the clinic and include frontline antimicrobial and anticancer drugs such as erythromycin and doxorubicin. To replenish the clinicians’ diminishing arsenal of bioactive molecules, a promising strategy aims at transferring polyketide biosynthetic pathways from their native producers into the biotechnologically desirable host Escherichia coli. This approach has been successful for type I modular polyketide synthases (PKSs); however, despite more than 3 decades of research, the large and important group of type II PKSs has until now been elusive in E. coli. Here, we report on a versatile polyketide biosynthesis pipeline, based on identification of E. coli–compatible type II PKSs. We successfully express 5 ketosynthase (KS) and chain length factor (CLF) pairs—e.g., from Photorhabdus luminescens TT01, Streptomyces resistomycificus, Streptoccocus sp. GMD2S, Pseudoalteromonas luteoviolacea, and Ktedonobacter racemifer—as soluble heterodimeric recombinant proteins in E. coli for the first time. We define the anthraquinone minimal PKS components and utilise this biosynthetic system to synthesise anthraquinones, dianthrones, and benzoisochromanequinones (BIQs). Furthermore, we demonstrate the tolerance and promiscuity of the anthraquinone heterologous biosynthetic pathway in E. coli to act as genetically applicable plug-and-play scaffold, showing it to function successfully when combined with enzymes from phylogenetically distant species, endophytic fungi and plants, which resulted in 2 new-to-nature compounds, neomedicamycin and neochaetomycin. This work enables plug-and-play combinatorial biosynthesis of aromatic polyketides using bacterial type II PKSs in E. coli, providing full access to its many advantages in terms of easy and fast genetic manipulation, accessibility for high-throughput robotics, and convenient biotechnological scale-up. Using the synthetic and systems biology toolbox, this plug-and-play biosynthetic platform can serve as an engine for the production of new and diversified bioactive polyketides in an automated, rapid, and versatile fashion.

Direct cation-exchange of a homogeneous organometallic cationic molecular catalyst inside the pores of an anionic MOF is conclusively demonstrated., Metal–Organic Frameworks (MOFs) are porous crystalline materials that have emerged as promising hosts for the heterogenization of homogeneous organometallic catalysts, forming hybrid materials which combine the benefits of both classes of catalysts. Herein, we report the encapsulation of the organometallic cationic Lewis acidic catalyst [CpFe(CO)2(L)]+ ([Fp–L]+, Cp = η5-C5H5, L = weakly bound solvent) inside the pores of the anionic [Et4N]3[In3(BTC)4] MOF (H3BTC = benzenetricarboxylic acid) via a direct one-step cation exchange process. To conclusively validate this methodology, initially [Cp2Co]+ was used as an inert spatial probe to (i) test the stability of the selected host; (ii) monitor the stoichiometry of the cation exchange process and (iii) assess pore dimensions, spatial location of the cationic species and guest-accessible space by single crystal X-ray crystallography. Subsequently, the quasi-isosteric [Fp–L]+ was encapsulated inside the pores via partial cation exchange to form [(Fp–L)0.6(Et4N)2.4][In3(BTC)4]. The latter was rigorously characterized and benchmarked as a heterogeneous catalyst in a simple Diels–Alder reaction, thus verifying the integrity and reactivity of the encapsulated molecular catalyst. These results provide a platform for the development of heterogeneous catalysts with chemically and spatially well-defined catalytic sites by direct exchange of cationic catalysts into anionic MOFs.

In order to develop new porous materials for applications in gas separations such as natural gas upgrading, landfill gas processing and acetylene purification it is vital to gain understanding of host-substrate interactions at a molecular level. Herein we report a series of six isoreticular metal-organic frameworks (MOFs) for selective gas adsorption. These materials do not incorporate open metal sites and thus provide an excellent platform to investigate the effect of the incorporation of ligand functionality via amide and alkyne groups on substrate binding. By reducing the linker length of our previously reported MFM-136, we report much improved CO2/CH4 (50:50) and CO2/N2 (15:85) selectivity values of 20.2 and 65.4, respectively (1 bar and 273 K), in the new amide-decorated MOF, MFM-126. The CO2 separation performance of MFM-126 has been confirmed by dynamic breakthrough experiments. In situ inelastic neutron scattering and synchrotron FT-IR microspectroscopy were employed to elucidate dynamic interactions of adsorbed CO2 molecules within MFM-126. Upon changing the functionality to an alkyne group in MFM-127, the CO2 uptake decreases but the C2H2 uptake increases by 68%, leading to excellent C2H2/CO2 and C2H2/CH4 selectivities of 3.7 and 21.2, respectively. Neutron powder diffraction enabled the direct observation of the preferred binding domains in MFM-126 and MFM-127, and, to the best of our knowledge, we report the first example of acetylene binding to an alkyne moiety in a porous material, with over 50% of the acetylene observed within MFM-127 displaying interactions (less than 4 Å) with the alkyne functionality of the framework.

2-Imidazolines are heterocycles with a wide range of applications in biomedical science, pharmaceuticals, surfactants and catalysis. The 2,4,5-trisubstituted derivatives are conventionally prepared through the reaction of aromatic aldehydes and ammonia, requiring harsh conditions and toxic solvents. Herein, we report a sustainable, one-pot synthetic route to obtain cis or trans diastereomers of 2,4,5-trisubstituted-2-imidazolines. The reaction parameters such as the ammonia source, the substituents of the aromatic aldehydes, the effect of temperature and solvent, were systematically explored. The synthesis was attempted in sixteen different green solvents. Reaction kinetic and quantum mechanical studies (DFT B3LYP/6-31G(d,p)) revealed the elementary steps of the cyclisation and refuted two common speculations. The limitations of the synthesis were explored through varying the p-, o-, and m-substituents on the aldehyde as well as employing heterocyclic and non-aromatic derivatives. Ten out of the twelve products synthesised in this work can be solely purified by crystallisation, without the need for extraction or chromatography. Due to the bulky nature of the products, the applicability of membrane-based purification was demonstrated to further improve the sustainability of the synthesis.