Fragment-Guided Genome Mining of Octacyclic Cyclophane Alkaloids from Fungi.

Nature uses compact but functionalized biosynthetic fragments as building blocks to generate complex natural products. To leverage this strategy for the discovery of natural products with new scaffolds, we performed genome mining to identify biosynthetic gene clusters (BGCs) in fungi that embed genes that can synthesize targeted fragments. The three-enzyme pathway that biosynthesizes the strained dityrosine cyclophane in the herquline A pathway was used to identify a large number of potential BGCs that may use the cyclophane as a fragment. Characterization of a conserved BGC from fungal strains led to the isolation of octacyclin A, an octacyclic natural product with an unprecedented structure, including two hetero-[3.3.1]bicycles and a combination of fused, bridged, and macrocyclic rings. Biosynthetic steps leading to octacyclin A were fully elucidated using pathway reconstitution and enzymatic assays, unveiling intriguing chemical logic and new enzymatic reactions in building the octacyclic core. Our work demonstrates the potential utility of fragment-guided genome mining in expanding natural product chemical space.

Toward liquid cell quantum sensing: Ytterbium complexes with ultranarrow absorption.

The energetic disorder induced by fluctuating liquid environments acts in opposition to the precise control required for coherence-based sensing. Overcoming fluctuations requires a protected quantum subspace that only weakly interacts with the local environment. We report a ytterbium complex that exhibited an ultranarrow absorption linewidth in solution at room temperature with a full width at half maximum of 0.625 milli-electron volts. Using spectral hole burning, we measured an even narrower linewidth of 410 pico-electron volts at 77 kelvin. Narrow linewidths allowed low-field magnetic circular dichroism at room temperature, used to sense Earth-scale magnetic fields. These results demonstrated that ligand protection in lanthanide complexes could substantially diminish electronic state fluctuations. We have termed this system an "atomlike molecular sensor" (ALMS) and proposed approaches to improve its performance.

Atomically precise inorganic helices with a programmable irrational twist.

Helicity in solids often arises from the precise ordering of cooperative intra- and intermolecular interactions unique to natural, organic or molecular systems. This exclusivity limited the realization of helicity and its ensuing properties in dense inorganic solids. Here we report that Ga atoms in GaSeI, a representative III-VI-VII one-dimensional (1D) van der Waals crystal, manifest the rare Boerdijk-Coxeter helix motif. This motif is a non-repeating geometric pattern characterized by 1D face-sharing tetrahedra whose adjacent vertices are rotated by an irrational angle. Using InSeI and GaSeI, we show that the modularity of 1D van der Waals lattices accommodates the systematic twisting of a periodic tetrahelix with a 41 screw axis in InSeI to an infinitely extending Boerdijk-Coxeter helix in GaSeI. GaSeI crystals are non-centrosymmetric, optically active and exfoliable to a single chain. These results present a materials platform towards understanding the origin and physical manifestation of aperiodic helicity in low-dimensional solids.

Ultrafast Au(III)-Mediated Arylation of Cysteine.

Through mechanistic work and rational design, we have developed the fastest organometallic abiotic Cys bioconjugation. As a result, the developed organometallic Au(III) bioconjugation reagents enable selective labeling of Cys moieties down to picomolar concentrations and allow for the rapid construction of complex heterostructures from peptides, proteins, and oligonucleotides. This work showcases how organometallic chemistry can be interfaced with biomolecules and lead to a range of reactivities that are largely unmatched by classical organic chemistry tools.

Charge and Solvent Effects on the Redox Behavior of Vanadyl Salen-Crown Complexes.

The incorporation of charged groups proximal to a redox active transition metal center can impact the local electric field, altering redox behavior and enhancing catalysis. Vanadyl salen (salen = N,N'-ethylenebis(salicylideneaminato)) complexes functionalized with a crown ether containing a nonredox active metal cation (V-Na, V-K, V-Ba, V-La, V-Ce, and V-Nd) were synthesized. The electrochemical behavior of this series of complexes was investigated by cyclic voltammetry in solvents with varying polarity and dielectric constant (ε) (acetonitrile, ε = 37.5; N,N-dimethylformamide, ε = 36.7; and dichloromethane, ε = 8.93). The vanadium(V/IV) reduction potential shifted anodically with increasing cation charge compared to a complex lacking a proximal cation (ΔE1/2 > 900 mV in acetonitrile and >700 mV in dichloromethane). In contrast, the reduction potential for all vanadyl salen-crown complexes measured in N,N-dimethylformamide was insensitive to the magnitude of the cationic charge, regardless of the electrolyte or counteranion used. Titration studies of N,N-dimethylformamide into acetonitrile resulted in cathodic shifting of the vanadium(V/IV) reduction potential with increasing concentration of N,N-dimethylformamide. Binding constants of N,N-dimethylformamide (log(KDMF)) for the series of crown complexes show increased binding affinity in the order of V-La > V-Ba > V-K > (salen)V(O), indicating an enhancement of Lewis acid/base interaction with increasing cationic charge. The redox behavior of (salen)V(O) and (salen-OMe)V(O) (salen-OMe = N,N'-ethylenebis(3-methoxysalicylideneamine) was also investigated and compared to the crown-containing complexes. For (salen-OMe)V(O), a weak association of triflate salt at the vanadium(IV) oxidation state was observed through cyclic voltammetry titration experiments, and cation dissociation upon oxidation to vanadium(V) was identified. These studies demonstrate the noninnocent role of solvent coordination and cation/anion effects on redox behavior and, by extension, the local electric field.

Synthesis, structural studies, and redox chemistry of bimetallic [Mn(CO)3] and [Re(CO)3] complexes.

Manganese ([Mn(CO)3]) and rhenium tricarbonyl ([Re(CO)3]) complexes represent a workhorse family of compounds with applications in a variety of fields. Here, the coordination, structural, and electrochemical properties of a family of mono- and bimetallic [Mn(CO)3] and [Re(CO)3] complexes are explored. In particular, a novel heterobimetallic complex featuring both [Mn(CO)3] and [Re(CO)3] units supported by 2,2'-bipyrimidine (bpm) has been synthesized, structurally characterized, and compared to the analogous monomeric and homobimetallic complexes. To enable a comprehensive structural analysis for the series of complexes, we have carried out new single crystal X-ray diffraction studies of seven compounds: Re(CO)3Cl(bpm), anti-[{Re(CO3)Cl}2(bpm)], Mn(CO)3Br(bpz) (bpz = 2,2'-bipyrazine), Mn(CO)3Br(bpm), syn- and anti-[{Mn(CO3)Br}2(bpm)], and syn-[Mn(CO3)Br(bpm)Re(CO)3Br]. Electrochemical studies reveal that the bimetallic complexes are reduced at much more positive potentials (ΔE≥ 380 mV) compared to their monometallic analogues. This redox behavior is consistent with introduction of the second tricarbonyl unit which inductively withdraws electron density from the bridging, redox-active bpm ligand, resulting in more positive reduction potentials. [Re(CO3)Cl]2(bpm) was reduced with cobaltocene; the electron paramagnetic resonance spectrum of the product exhibits an isotropic signal (near g = 2) characteristic of a ligand-centered bpm radical. Our findings highlight the facile synthesis as well as the structural characteristics and unique electrochemical behavior of this family of complexes.

Reducing CO2 to HCO2- at Mild Potentials: Lessons from Formate Dehydrogenase.

The catalytic reduction of CO2 to HCO2- requires a formal transfer of a hydride (two electrons, one proton). Synthetic approaches for inorganic molecular catalysts have exclusively relied on classic metal hydrides, where the proton and electrons originate from the metal (via heterolytic cleavage of an M-H bond). An analysis of the scaling relationships that exist in classic metal hydrides reveal that hydride donors sufficiently hydridic to perform CO2 reduction are only accessible at very reducing electrochemical potentials, which is consistent with known synthetic electrocatalysts. By comparison, the formate dehydrogenase enzymes operate at relatively mild potentials. In contrast to reported synthetic catalysts, none of the major mechanistic proposals for hydride transfer in formate dehydrogenase proceed through a classic metal hydride. Instead, they invoke formal hydride transfer from an orthogonal or bidirectional mechanism, where the proton and electrons are not colocated. We discuss the thermodynamic advantages of this approach for favoring CO2 reduction at mild potentials, along with guidelines for replicating this strategy in synthetic systems.

Intensified Electrocatalytic CO2 Conversion in Pressure-Tunable CO2 -Expanded Electrolytes.

Multimolar CO2 concentrations are achieved in acetonitrile solutions containing supporting electrolyte at relatively mild CO2 pressures (<5 MPa) and ambient temperature. Such CO2 -rich, electrolyte-containing solutions are termed as CO2 -eXpanded Electrolytes (CXEs) because significant volumetric expansion of the liquid phase accompanies CO2 dissolution. Cathodic polarization of a model polycrystalline gold electrode-catalyst in CXE media enhances CO2 to CO conversion rates by up to an order of magnitude compared with those attainable at near-ambient pressures, without loss of selectivity. The observed catalytic process intensification stems primarily from markedly increased CO2 availability. However, a non-monotonic correlation between the dissolved CO2 concentration and catalytic activity is observed, with an optimum occurring at approximately 5 m CO2 concentration. At the highest applied CO2 pressures, catalysis is significantly attenuated despite higher CO2 concentrations and improved mass-transport characteristics, attributed in part to increased solution resistance. These results reveal that pressure-tunable CXE media can significantly intensify CO2 reduction rates over known electrocatalysts by alleviating substrate starvation, with CO2 pressure as a crucial variable for optimizing the efficiency of electrocatalytic CO2 conversion.