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Hydrogen gas and its production from renewable power sources will be an important part of decreasing global reliance on fossil fuels and developing a sustainable energy economy. Efficient electrocatalysis, however, relies on the delivery of both protons and electrons; ideally in a concerted fashion to avoid high energy intermediates, prevent charge build‐up, and circumvent large kinetic barriers. While this can be achieved using ligand design in homogenous molecular transition metal catalysts (specifically incorporating proton shuttles in the secondary coordination sphere), heterogeneous systems are more desirable from an industrial perspective due to their ease of use and enhanced durability. Supporting transition metal catalysts on electrode surfaces is therefore a promising approach for developing next generation electrocatalysts that retain molecular level control in interfacial environments. This review will first cover key design principles from natural systems, such as hydrogenase enzymes, and then survey some representative examples of synthetic homogeneous hydrogen evolution electrocatalysts that incorporate these important features. We will then discuss transition metal species that have been supported on electrode materials, with a focus on recent advances in the field, and the major challenges that remain. [ABSTRACT FROM AUTHOR]

Knölker complexes have been recently used to perform the catalytic C1‐oxidation of unprotected sugars into sugar lactones. This oxidation method remained limited by the stability of the catalyst with the polyhydroxylated substrates. Our objective is now to overcome these limitations and extend this method to more challenging substrates such as disaccharides. We proposed in this paper two original designs of Knölker‐type complexes conceived to promote secondary H‐bond interactions with the OH groups of the substrates to stabilise the system and favour the transformation. In total, 8 novel pre‐catalysts were synthesised, fully characterised and applied in the anomeric oxidation of several sugar derivatives. Two of these new complexes proved to be more efficient than the Knölker complex for the oxidation of disaccharides. Moreover, a preliminary DFT study revealed the presence of H‐bonds interactions between the substrate and the oxygen atom on the ligand arm of the best complexes suggesting a beneficial role of this heteroatom on the catalytic efficiency. [ABSTRACT FROM AUTHOR]

The development of palladium‐catalyzed fluorination with biaryl monophosphine ligands has faced two important problems that limit its application for bromoarenes: the formation of regioisomers and insufficient catalysis for heteroaryl substrates as bromothiophene derivatives. Overcoming these problems requires more ligand design. In this work, reliable theoretical calculations were used to elucidate important ligand features necessary for achieving more rate acceleration and selectivity. These features include increasing the ligand‐substrate repulsion and creating a negative charge in the space around the fluoride ion bonded to the palladium. The investigated L5 ligand presents these features, and the calculations predict that this ligand completely suppresses the regioisomer formation in the difficult case of 4‐bromoanisole. In addition, the free energy barriers are decreased by 2–3 kcal mol−1 in comparison with the catalysis involving the AlPhos ligand. Thus, the present study points out a direction for new developments in palladium‐catalyzed fluorination. [ABSTRACT FROM AUTHOR]

Pd(II)‐catalyzed enantioselective C−H activation has emerged as a versatile platform for constructing point, axial, and planar chirality. Herein, we present an unexpected discovery of a Pd‐catalyzed enantioselective cascade β,γ‐methylene C(sp3)−H diarylation of free carboxylic acids using bidentate chiral mono‐protected amino thioether ligands (MPAThio), enabling one‐step synthesis of a complex chiral 9,10‐dihydrophenanthrene scaffolds with high enantioselectivity. In this process, two methylene C(sp3)−H bonds and three C(sp2)−H bonds were activated, leading to the formation of four C−C bonds and three chiral centers in one pot. A plausible catalytic pathway starts with enantioselective β,γ‐dehydrogenation to form chiral β,γ‐cyclohexene. Intriguingly, this olefin serves as a norbornene‐type reagent (presumably assisted by the carboxyl directing effect), relaying two successive Catellani arylation reactions and a C−H arylation reaction to furnish chiral 9,10‐dihydrophenanthrenes along with meta‐selective homocoupling products of iodoarene. [ABSTRACT FROM AUTHOR]

The introduction of fluorine atom has attracted considerable interest in molecular design owing to the high electronegativity and the resulting polarization of carbon–fluorine bonds. Simultaneously, sterically‐hindered N‐heterocyclic carbenes (NHCs) have received major interest due to high stabilization of the reactive metal centers, which has paved the way for the synthesis of stable and reactive organometallic compounds with broad applications in main group chemistry, inorganic synthesis and transition‐metal‐catalysis. Herein, we report the first class of sterically‐hindered, fluorinated N‐heterocyclic carbenes. These ligands feature variable fluorine substitution at the N‐aromatic wingtip, permitting to rationally vary steric and electronic characteristics of the carbene center imparted by the fluorine atom. An efficient, one‐pot synthesis of fluorinated IPr*F ligands is presented, enabling broad access of academic and industrial researchers to the fluorinated ligands. The evaluation of steric, electron‐donating and π‐accepting properties as well as coordination chemistry to Au(I), Rh(I) and Se is presented. Considering the unique properties of carbon–fluorine bonds, we anticipate that this novel class of fluorinated carbene ligands will find widespread application in stabilizing reactive metal centers. [ABSTRACT FROM AUTHOR]

A three‐component coupling approach toward structurally complex dialkylsulfides is described via the nickel‐catalyzed 1,2‐carbosulfenylation of unactivated alkenes with organoboron nucleophiles and alkylsulfenamide (N−S) electrophiles. Efficient catalytic turnover is facilitated using a tailored N−S electrophile containing an N‐methyl methanesulfonamide leaving group, allowing catalyst loadings as low as 1 mol %. Regioselectivity is controlled by a collection of monodentate, weakly coordinating native directing groups, including sulfonamides, amides, sulfinamides, phosphoramides, and carbamates. Key to the development of this transformation is the identification of quinones as a family of hemilabile and redox‐active ligands that tune the steric and electronic properties of the metal throughout the catalytic cycle. Density functional theory (DFT) results show that the duroquinone (DQ) ligand adopts different coordination modes in different stages of the Ni‐catalyzed 1,2‐carbosulfenylation‐binding as an η6 capping ligand to stabilize the precatalyst/resting state and prevent catalyst decomposition, binding as an X‐type redox‐active durosemiquinone radical anion to promote alkene migratory insertion with a less distorted square planar Ni(II) center, and binding as an L‐type ligand to promote N−S oxidative addition at a relatively more electron‐rich Ni(I) center. [ABSTRACT FROM AUTHOR]

Electrochromism is the process by which a material applies a small electrical signal to change the optical properties (transmittance, reflectance, absorptivity and emissivity) of the material reversibly or permanently through REDOX reactions resulting from ion and electron embedding/ejection. Metal-organic framework (MOF) are advantageous materials for electrochromic application due to their high porosity, large specific surface area and orderly pore structure, that promotes the adsorption of electrolyte ions, ion diffusion and charge transfer. In addition, MOFs possess a variety of ligands and metal centers, allowing for design of composition types and pore structure sizes. This grants them the advantages of both organic electrochromic materials, such as vivid colors and fast color transformation, and inorganic electrochromic materials, like high coloring efficiency and excellent stability. This paper reviews the current research progress of MOF electrochromic materials, including materials design, electrochromic properties, and application.

Sterically loaded, anionic pyridine has been synthesized and utilized successfully in the stabilization of a isoleptic series of coinage metal complexes. The treatment of [4‐(Ph3B)‐2,6‐Trip2Py]K (Trip=2,4,6‐iPr3C6H2) with CuBr(PPh3), AgCl(PPh3) or AuCl(PPh3) (Py=pyridine) afforded the corresponding [4‐(Ph3B)‐2,6‐Trip2Py]M(PPh3) (M=Au, Ag, Cu) complexes, via salt metathesis, as isolable, crystalline solids. Notably, these reactions avoid the facile single electron transfer chemistry reported with the less bulky ligand systems. The X‐ray structures revealed that they are two‐coordinate metal adducts. The M−N and M−P bond distances are longest in the silver and shortest in the copper adduct among the three group 11 family members. Computational analysis revealed an interesting stability dependence on steric bulk of the anionic pyridine (i. e., pyridyl borate) ligand. A comparison of structures and bonding of [4‐(Ph3B)‐2,6‐Trip2Py]Au(PPh3) to pyridine and m‐terphenyl complexes, {[2,6‐Trip2Py]Au(PPh3)}[SbF6] and [2,6‐Trip2Ph]Au(PPh3) are also provided. The Au(I) isocyanide complex, [4‐(Ph3B)‐2,6‐Trip2Py]Au(CNBut) has been stabilized using the same anionic pyridylborate illustrating that it can support other gold‐ligand moieties as well. [ABSTRACT FROM AUTHOR]

A Cu/Co tandem catalysis protocol was developed to conduct the hydroformylation of olefins using CO2/H2 and PMHS (polymethylhydrosiloxane) as a readily available and environmentally friendly hydride source. This methodology was performed via a two‐step approach consisting of the copper‐catalyzed reduction of CO2 by hydrosilane and subsequent cobalt‐promoted hydroformylation with H2 and the in situ formed CO. The optimized triphos oxide ligand, which presumably facilitates the migratory insertion of CO gives moderate to excellent yields for both terminal and internal alkenes. This earth‐abundant metal catalysis provides a reliable and efficient way to afford useful aldehydes in industry using silicon by‐product PMHS as hydrogen source and renewable CO2 as carbonyl source. [ABSTRACT FROM AUTHOR]

Alkyl chlorides are a class of versatile building blocks widely used to generate C(sp3)‐rich scaffolds through transformation such as nucleophilic substitution, radical addition reactions and metal‐catalyzed cross‐coupling processes. Despite their utility in the synthesis of high‐value functional molecules, distinct methods for the preparation of alkyl chlorides are underrepresented. Here, we report a visible‐light‐mediated dual catalysis strategy for the modular synthesis of highly functionalized and structurally diverse arylated chloroalkanes via the coupling of diaryliodonium salts, alkenes and potassium chloride. A distinctive aspect of this transformation is a ligand‐design‐driven approach for the development of a copper(II)‐based atom‐transfer catalyst that enables the aryl‐chlorination of electron‐poor alkenes, complementing its iron(III)‐based counterpart that accommodates non‐activated aliphatic alkenes and styrene derivatives. The complementarity of the two dual catalytic systems allows the efficient aryl‐chlorination of alkenes bearing different stereo‐electronic properties and a broad range of functional groups, maximizing the structural diversity of the 1‐aryl, 2‐chloroalkane products. [ABSTRACT FROM AUTHOR]

To qualify as competent sorbents for airborne contaminants such as iodine vapor, permanent porosity and chemical stability are key criteria for the selection of candidate metal-organic frameworks (MOFs). To ensure these characteristics, in the present study, an unsymmetrical bifunctional ligand incorporating both carboxylic acid and hydroxamic acid groups was employed for MOF [Zn(CBHA)](DMF) [SUM-13; CPHA = 4-carboxyphenylhydroxamate, DMF = N,N-dimethylformamide] design and synthesis. Though coupled with Zn2+, which does not typically yield kinetically robust MOFs with hard acids, the SUM-13 featuring differentiated coordination modes of chelating, bridging and monodentate bonding exhibited exceptional chemical stability and permanent porosity, with a Brunauer–Emmett–Teller (BET) surface area of 296.9 m2/g and a total pore volume of 0.1196 cm3/g. Additionally, with porosity and open metal sites at the five-coordinate Zn2+ centers, SUM-13 was demonstrated to be an eligible iodine adsorbent, reaching a maximum uptake of 796 mg/g. These findings underscore the validity and potential of the design strategy in constructing stable metal–organic frameworks. [ABSTRACT FROM AUTHOR]

Alternating current (AC) and pulsed electrolysis are gaining traction in electro(organic) synthesis due to their advantageous characteristics. We employed AC electrolysis in electrochemically mediated Atom Transfer Radical Polymerization (eATRP) to facilitate the regeneration of the activator CuI complex on Cu0 electrodes. Additionally, Cu0 served as a slow supplemental activator and reducing agent (SARA ATRP), enabling the activation of alkyl halides and the regeneration of the CuI activator through a comproportionation reaction. We harnessed the distinct properties of Cu0 dual regeneration, both chemical and electrochemical, by employing sinusoidal, triangular, and square‐wave AC electrolysis alongside some of the most active ATRP catalysts available. Compared to linear waveform (DC electrolysis) or SARA ATRP (without electrolysis), pulsed and AC electrolysis facilitated slightly faster and more controlled polymerizations of acrylates. The same AC electrolysis conditions could successfully polymerize eleven different monomers across different mediums, from water to bulk. Moreover, it proved effective across a spectrum of catalyst activity, from low‐activity Cu/2,2‐bipyridine to highly active Cu complexes with substituted tripodal amine ligands. Chain extension experiments confirmed the high chain‐end fidelity of the produced polymers, yielding functional and high molecular‐weight block copolymers. SEM analysis indicated the robustness of the Cu0 electrodes, sustaining at least 15 consecutive polymerizations. [ABSTRACT FROM AUTHOR]

A class of novel chiral‐bridged biphenyl monophosphine ligands with a benzofuran moiety (He‐phos) has been successfully synthesized and reported. These ligands exhibited good performance in the gold‐catalyzed enantioselective cycloaddition reaction of 2‐(1‐alkynyl)‐2‐en‐1‐ones with nitrones, resulting in the successful preparation of a series of polyaryl‐substituted heterocyclic compounds with high enantioselectivities (up to 99% yield, 98% ee). The wide substrate adaptability (53 examples) and mild reaction conditions demonstrate the practicability of He‐phos in this reaction. [ABSTRACT FROM AUTHOR]

Carbon dioxide (CO2) is a potent greenhouse gas of environmental concern. Seeking to offer a solution to the "CO2‐problem", the chemistry community has turned a focus toward transition metal complexes which can activate, reduce, and convert CO2 into carbon‐based products. The design of such systems involves judicious selection of both metal and accompanying donor ligand; in part, these efforts are motivated by biological metalloenzymes that undertake similar transformations. As a design element, metal‐ligand cooperativity, which leverages intramolecular interactions between a transition metal and an adjacent secondary ligand site, has been acknowledged as a vitally important component by the CO2 activation community. These systems offer a "push‐pull" style of activation where electron density is chaperoned onto CO2 with an accompanying electrophile, such as a Lewis‐acid, playing the role of acceptor. This pairing allows for the stabilization of reactive CxHyOz‐containing intermediates and can bias CO2 product selectivity. In the laboratory, chemists can test hypotheses and ideas, enabling rationalization of why a given pairing of transition metal/Lewis‐acid leads to selective CO2 reduction outcomes. This Concept identifies literature examples and highlights key design properties, allowing interested contributors to design, create, and implement novel systems for productive transformations of a small molecule (CO2) with huge potential impact. [ABSTRACT FROM AUTHOR]

The tau-tubulin kinase 1 (TTBK1) protein is a casein kinase 1 superfamily member located at chromosome 6p21.1. It is expressed explicitly in the brain, particularly in the cytoplasm of cortical and hippocampal neurons. TTBK1 has been implicated in the phosphorylation and aggregation of tau in Alzheimer's disease (AD). Considering its significance in AD, TTBK1 has emerged as a promising target for AD treatment. In the present study, we identified novel TTBK1 inhibitors using various computational techniques. We performed a virtual screening-based docking study followed by E-pharmacophore modeling, cavity-based pharmacophore, and ligand design techniques and found ZINC000095101333, LD7, LD55, and LD75 to be potential novel TTBK1 lead inhibitors. The docking results were complemented by Molecular Mechanics/Generalized Born Surface Area (MMGBSA) calculations. The molecular dynamics (MD) simulation studies at a 500 ns scale were carried out to monitor the behavior of the protein toward the identified ligands. Pharmacological and ADME/T studies were carried out to check the drug-likeness of the compounds. In summary, we identified a new series of compounds that could effectively bind the TTBK1 receptor. The newly designed compounds are promising candidates for developing therapeutics targeting TTBK1 for AD. [ABSTRACT FROM AUTHOR]

A universally applicable synthesis route for the preparation of functionalized diazabicyclononane compounds was elaborated starting from a readily available 1,5‐diphenyl‐3,7‐diazabicyclo[3.3.1] nonan‐9‐ol by alkylation of both secondary amines with modified benzyl residues containing a bromo, trimethylstannyl, trimethylsilyl, and pinacolboranyl residue. High yields (65–88 %) were achieved, supporting the intended purpose of these compounds: efficient mercuration reactions to stably bind Hg2+. Finally, the C‐9 position of two functionalized diazabicyclononanes was further modified by introducing an azide functionality. This enables the conjugation to biomolecules of interest via click chemistry combined with a tracking by the introduced mercury isotopes. [ABSTRACT FROM AUTHOR]

We developed a dinucleating ligand system with two identical tetradentate coordination compartments and varying terminal donors. Here, we report the synthesis of two differently asymmetric dinucleating ligands: the ligand selma (=4,7,10‐trimethyl‐1,1,10‐tris(2‐pyridylmethyl)‐1,4,7,10‐tetraazadecane) with one N3‐ and one N4‐ and the ligand susanH2Me2 ${{^{{\rm H}{_{2}}{\rm Me}{_{2}}}}}$ (=4,7‐dimethyl‐1,1‐bis(6‐methylpyridine‐2‐yl‐methyl)‐10,10‐bis(2‐pyridylmethyl)‐1,4,7,10‐tetraazadecane) with two different N4‐coordination compartments. The initial synthesis of the ligand selma based on extending dipicolylamine with 2‐(methylamino)ethyl units in repeated reductive aminations. Synthesis of 1‐trifluoroacetyl‐4,7‐dimethyl‐1,4,7,10‐tetraazadecane allowed the synthesis of both ligands selma and susanH2Me2 ${{^{{\rm H}{_{2}}{\rm Me}{_{2}}}}}$. To study the influence of the terminal donors, the CuII chloride complexes of selma and susanH2Me2 ${{^{{\rm H}{_{2}}{\rm Me}{_{2}}}}}$ and the two symmetric susan and susan6−Me were synthesized. The introduction of the 6‐methyl substituents on the pyridines increases the bond lengths, reduces the electron donation, and shifts the reduction potentials anodically. The large 6‐methyl substituents enforce a meridional coordination of the dipicolylamine subunits, while it is mainly facial without the 6‐methyl substituents. Analysis of the solid‐state structures and the d‐d transitions in solution demonstrate a flat potential energy surface for the 5‐coordinate polyhedra. Analysis of d‐d transitions and reduction potentials indicate that the properties of the CuIICuII complexes are additive for but cooperative for selma reflecting the difference of these asymmetric dinucleating ligands. [ABSTRACT FROM AUTHOR]

The reaction between bis(1,2,3‐triazol‐1‐yl)methane derivatives and nBuLi and various aldehydes, yielded novel neutral ligand precursors incorporating alcohol functional groups. The resulting compounds exhibited distinct characteristics depending on the steric hindrance of the aldehyde employed. In instances where aromatic aldehydes were utilized, functionalization occurred at the methine group bridging both triazole rings. Conversely, the use of pivalic aldehyde prompted functionalization at the C5 position of the triazole ring. These compounds were subsequently employed as ligand precursors in the synthesis of organometallic aluminum and zinc complexes, yielding dinuclear complexes with high efficiency. The structural elucidation of all compounds was accomplished through spectroscopic methods and validated by X‐ray crystallography. Preliminary catalytic investigations into the coupling reaction of cyclohexene oxide and CO2 revealed that aluminum and zinc complexes catalyzed the selective formation of polyether and polycarbonate materials, respectively. [ABSTRACT FROM AUTHOR]

We report a series of Pd(II)nL2n coordination rings for which nuclearity is controlled by the binding angle of the corresponding bis‐monodentate bridging ligands. Judicious choice of the angle within a family of rather rigid ligands allowed for the first‐time to synthesize a homoleptic five‐membered Pd5L10 ring that does not require any template to form. We demonstrate that control over the ring size is maintained both in the solid‐, solution‐, and gas‐phase. Two X‐ray structures of five‐membered rings from ligands with ideal angles (yielding a perfect pentagonal ring) vs. suboptimal angles (resulting in a highly distorted structure) illustrate the importance of the correct ligand geometry. A mathematical model for estimating the expected ring size based on the ligand angle was derived and DFT computations show that ring‐strain is the major factor determining the assembly outcome. [ABSTRACT FROM AUTHOR]

Herein, multiple types of chiral Os(II) complexes have been designed to address the appealing yet challenging asymmetric C(sp3)−H functionalization, among which the Os(II)/Salox species is found to be the most efficient for precise stereocontrol in realizing the asymmetric C(sp3)−H amidation. As exemplified by the enantioenriched pyrrolidinone synthesis, such tailored Os(II)/Salox catalyst efficiently enables an intramolecular site‐/enantioselective C(sp3)−H amidation in the γ‐position of dioxazolone substrates, in which benzyl, propargyl and allyl groups bearing various substituted forms are well compatible, affording the corresponding chiral γ‐lactam products with good er values (up to 99 : 1) and diverse functionality (>35 examples). The unique performance advantage of the developed chiral Os(II)/Salox system in terms of the catalytic energy profile and the chiral induction has been further clarified by integrated experimental and computational studies. [ABSTRACT FROM AUTHOR]

We disclose the development of a Cu‐catalyzed C−O coupling method utilizing a new N1,N2‐diarylbenzene‐1,2‐diamine ligand, L8. Under optimized reaction conditions, structurally diverse aryl and heteroaryl bromides underwent efficient coupling with a variety of alcohols at room temperature using an L8‐based catalyst. Notably, the L8‐derived catalyst exhibited enhanced activity when compared to the L4‐based system previously disclosed for C−N coupling, namely the ability to functionalize aryl bromides containing acidic functional groups. Mechanistic studies demonstrate that C−O coupling utilizing L8 ⋅ Cu involves rate‐limiting alkoxide transmetallation, resulting in a mechanism of C−O bond formation that is distinct from previously described Pd‐, Cu‐, or Ni‐based systems. This lower energy pathway leads to rapid C−O bond formation; a 7‐fold increase relative to what is seen with other ligands. The results presented in this report overcome limitations in previously described C−O coupling methods and introduce a new ligand that we anticipate may be useful in other Cu‐catalyzed C‐heteroatom bond‐forming reactions. [ABSTRACT FROM AUTHOR]

Over the years, phosphate ester hydrolysis catalyzed by coordination compounds has attracted extensive research on developing new bioinspired compounds. However, the literature lacks sufficient examples displaying activity toward phosphate triesters specifically, limiting the understanding of efficient strategies for the hydrolysis of this compound hydrolysis. Herein, we report preparing and characterizing three mononuclear iron(III) complexes (1, 2, and 3) and their hydrolase‐like activity. Complexes 2 and 3 have benzimidazole (BIMZ) moieties and were strategically designed to separate the BIMZ moiety from the first coordination sphere, and complex 1 (without BIMZ) was used as a reference. Several techniques provided structural information, including spectrophotometry, spectrometry, electrochemistry, elemental analysis, and 57Fe Mossbauer. Density functional theory (DFT) revealed distorted octahedral geometries due to the presence of the BIMZ groups. These groups also directly affected the protonation equilibria and catalytic activity. The phosphate triester diethyl‐2,4‐dinitrophenylphosphate (DEDNPP) hydrolysis was enhanced at least 27 times compared to the uncatalyzed reaction, with complexes 2 and 3, thus showing higher catalytic rates (kcat). Moreover, a longer carbon chain led to a higher hydrolysis rate but less interaction with substrate. These findings provide background for further investigations and the development of efficient catalysts for agrochemical degradation. [ABSTRACT FROM AUTHOR]

Trinuclear metallacyclic oxidovanadium(V) complexes, [{VO(L3+2R)}3] (1–3) with asymmetric multidentate linking ligands (H3L3+2R: R = H, Me, Br), were synthesized. The molecular structure of 1 is characterized as a tripod structure, with each V(V) ion coordinated by ONO-atoms from a tridentate Schiff base site and ON-atoms from a bidentate benzoxazole site of two respective H3L3+2H ligands. The intramolecular V⋯V distances range from 8.0683 to 8.1791 Å. Complex 4 is a mononuclear dioxidovanadium(V) complex, (Et3NH)[VO2(HL3+2H)]. Cyclic voltammograms of 1−3 in DMF revealed redox couples attributed to three single-electron transfer processes. [ABSTRACT FROM AUTHOR]

The development of the catalytic regio- and enantioselective hydrofunctionalization of 1,3-dienes remains a challenge and requires deep insight into the reaction mechanisms. We herein thoroughly studied the reaction mechanism of the Ni-catalyzed hydroalkylation of 1,3-dienes with ketones by density functional theory (DFT) calculations. It reveals that the reaction is initiated by stepwise oxidative addition of EtO-H followed by 1,3-diene migratory insertion to generate the alkylnickel(II) intermediate, rather than the experimentally proposed ligand-to-ligand hydrogen transfer (LLHT) mechanism. In addition, we rationalized the role of tBuOK in the subsequent addition of enolate of ketone and transmetalation process. Based on the whole catalysis, the C C reductive elimination step, turns out to be the rate- and enantioselectivity-determining step. Furthermore, we disclosed the origins of the regio- and enantioselectivity of the product, and found that the 1,2-selectivity lies in the combination effects of the ligand-substrate electrostatic interactions, orbital interactions and Pauli repulsions, while the enantioselectivity mainly arises from substrate-ligand steric repulsions. Based on mechanistic study, new biaryl bisphosphine ligands affording higher enantioselectivity were designed, which will help to improve current catalytic systems and develop new transition-metal-catalyzed hydroalkylations. [ABSTRACT FROM AUTHOR]

Neutral three‐coordinate iron alkylidenes of the form PN−Fe=CHR have been proposed as viable candidates for alkene metathesis. Indeed, during the final stages of preparing this current study, a separate report disclosed that dearomatized PN−Fe‐alkyl complexes are active precatalysts for ring‐opening metathesis polymerization (ROMP) of norbornene implicating PN−Fe=CHR species as possible intermediates. In yet another separate report, we prepared Zn analogues of PN−Fe‐alkyl complexes and herein provide an account for the synthesis, characterization, and reactivity of some new iron complexes with the same tBu substituted PN platform. [ABSTRACT FROM AUTHOR]

We report the room temperature dimerization of carbon monoxide mediated by C4/C5‐vicinal anionic dicarbenes Li(ADC) (ADC = ArC{(Dipp)NC}2; Dipp = 2,6‐iPr2C6H3; Ar = Ph, DMP (4‐Me2NC6H4), Bp (4‐PhC6H4)) to yield (E)‐ethene‐1,2‐bis(olate) (i.e. −O−C=C−O− = COen) bridged mesoionic carbene (iMIC) lithium compounds COen‐[(iMIC)Li]2 (COen‐[iMIC]2 = [ArC{(Dipp)NC}2(CO)]2) in quantitative yields. COen‐[(iMIC)Li]2 are highly colored stable solids, exhibit a strikingly small HOMO–LUMO energy gap, and readily undergo 2e‐oxidations with selenium, CuCl (or CuCl2), and AgCl to afford the dinuclear compounds COon‐[(iMIC)E]2 (E = Se, CuCl, AgCl) featuring a 1,2‐dione bridged neutral bis‐iMIC (i.e. COon‐[iMIC]2 = [ArC{(Dipp)NC}2(C=O)]2). COen‐[(iMIC)Li]2 undergo redox‐neutral salt metathesis reactions with LiAlH4 and (Et2O)2BeBr2 and afford COen‐[(iMIC)AlH2]2 and COen‐[(iMIC)BeBr]2, in which the dianionic COen‐moiety remains intact. All compounds have been characterized by NMR spectroscopy, mass spectrometry, and X‐ray diffraction. Stereoelectronic properties of COon‐[iMIC]2 are quantified by experimental and theoretical methods. [ABSTRACT FROM AUTHOR]

The novel bidentate PP and PN ligands o‐(Ph2P)−C6H4−C≡C−PPh2 (LPP) and o‐(Ph2P)−C6H4−4−(C5H9N−Me) (LPN), respectively, have been designed as long‐range "cis‐spanning" ligands for the stabilization of heterodinuclear complexes containing two metal atoms in close proximity. The synthesis of heterodinuclear, formal AuIPtII complexes with the ligand LPP is straightforward. In the course of a one‐pot reaction, a surprisingly high selectivity for the coordination of AuCl and Pt(CNC) (CNC=2,6‐diphenylpyridine‐o,o'‐diate) to the phenyl‐bound and the alkyne‐bound PPh2 sites of LPP is observed, respectively. Chloride abstraction from the resulting heterodinuclear complex [(ClAu)(o‐Ph2P)−C6H4−C≡C−PPh2(Pt{CNC})] with Ag[SbF6] causes metal–metal bond formation and the generation of the cationic complex [LPPAuPt(CNC)][SbF6]. The high site selectivity for the coordination of the two metals to LPP was investigated by stoichiometric reactions of the ligand with one equivalent of the corresponding precursors. While analogous complexation experiments with LPN have not been successful, the synthesis of the heterodinuclear complex [(ClAu)(o‐Ph2P)−C6H4−4‐(C5H9N−Me)(PtCl2{dmso})] and of [LPN(AuCl)2] confirm the ability of LPN to serve as a ditopic ligand. In this context, it is noteworthy that [LPN(AuCl)2] constitutes the first amine–AuCl complex featuring a tertiary amine. [ABSTRACT FROM AUTHOR]

Development of new chiral ligands is essentially important in the field of asymmetric metal catalysis. Bispidines, steming from natural alkaloids, represent an intriguing yet underexplored class of chiral ligands. In this article, we developed a series of bispidine‐based chiral ligands with chirality locked in the side chain, and explore their properties by applying in the palladium‐catalyzed asymmetric addition of arylboric acids to cyclic N‐sulfonyl ketimines. A S,N‐bispidine ligand was found especially efficient, affording a series of chiral benzosultams with a quaternary chiral center in excellent yields with excellent ee values. Density functional theory (DFT) calculations and crystal structure of catalyst helped to propose a reasonable mechanism including a possible transition state model to explain the origin of stereoselectivity. [ABSTRACT FROM AUTHOR]

In main group chemistry, the BDI ligand ([HC(C(Me)N(R))2]), more commonly known as NacNac, has proved indispensable over the last two decades. Within this work, we are introducing the hybrid NacNac‐akin ligand 3,3‐dimethyl‐2‐[2‐methyl‐2‐(2,6‐diisopropyl‐aniline)ethenyl]‐3H‐indolenine (DNI). On the basis of this novel ligand, alkali metal complexes [DNI(M1)] [M1=Li (3(OEt2)), Na (4(THF)3), and K (5(THF)3)] have been synthesized by facile deprotonation of the ligand's backbone. The reaction of DNI with AlH3 ⋅ NMe2Et led to the aluminium dihydride compound [DNI‐AlH2] (6) in excellent yield (90 %). Further synthesis of [DNI‐AlI2] (7), which is seen as a potential precursor for the aluminium(I) complex, was realized in the presence of 1.0 equiv. iodine with 6. All products 2–7 were completely characterized by 2D‐NMR, mass spectrometry, elemental analysis and SC‐XRD. Density functional theory calculations were performed to provide better understanding of their bonding characteristics and electronic structures. [ABSTRACT FROM AUTHOR]

Tethered N‐heterocyclic carbenes (NHCs) are an emerging class of ligand, as they feature all the desirable aspects of NHCs (ease of synthesis, high tunabilty) but also enable metal‐ligand cooperativity when combined with Lewis acidic metal centres due to the donor‐acceptor nature of the complexes formed. Herein we report a simple ethoxy‐tethered NHC for the stabilisation of Al(III) hydrides, resulting in the unexpected formation of a bicyclic N‐heterocyclic aminal (1). Compound 1 behaves as a metal hydride, capable of reducing benzophenone and carbodiimide to yield compounds 2 and 3, respectively. Furthermore, we show that 1 behaves as an efficient catalyst in the dehydrocoupling of amine‐boranes due to the hemi‐labile nature of the supporting ligand. [ABSTRACT FROM AUTHOR]

IMes (IMes=1,3‐bis(2,4,6‐trimethylphenyl)imidazol‐2‐ylidene) and IPr (IPr=1,3‐ bis(2,6‐diisopropylphenyl)imidazol‐2‐ylidene) represent by far the most frequently used N‐heterocyclic carbene ligands in homogeneous catalysis, however, despite numerous advantages, these ligands are limited by the lack of steric flexibility of catalytic pockets. We report a new class of unique unsymmetrical N‐heterocyclic carbene ligands that are characterized by freely‐rotatable N‐aromatic wingtips in the imidazol‐2‐ylidene architecture. The combination of rotatable N−CH2Ar bond with conformationally‐fixed N−Ar linkage results in a highly modular ligand topology, entering the range of geometries inaccessible to IMes and IPr. These ligands are highly reactive in Cu(I)‐catalyzed β‐hydroboration, an archetypal borylcupration process that has had a transformative impact on the synthesis of boron‐containing compounds. The most reactive Cu(I)‐NHC in this class has been commercialized in collaboration with MilliporeSigma to enable broad access of the synthetic chemistry community. The ligands gradually cover %Vbur geometries ranging from 37.3 % to 52.7 %, with the latter representing the largest %Vbur described for an IPr analogue, while retaining full flexibility of N‐wingtip. Considering the modular access to novel geometrical space in N‐heterocyclic carbene catalysis, we anticipate that this concept will enable new opportunities in organic synthesis, drug discovery and stabilization of reactive metal centers. [ABSTRACT FROM AUTHOR]

A family of dinuclear complexes was rationally designed to bind to two neighboring phosphate diesters of DNA by molecular recognition. Although these complexes bind strongly and irreversibly to DNA and induce apoptosis in cancer cells, a direct proof of the intended binding mode is missing. To mimic two neighboring phosphate diesters of DNA, we use here the dicarboxylate glutarate as a difunctional ligand. Starting from the acetate‐bound CuII2 complex, protonation results in the de‐coordination of acetate and allows the synthesis of the glutarate‐bound complex. Instead of bridging two CuII ions of one dinuclear complex, two glutarates bridge two dinuclear complexes resulting in a tetranuclear metallo‐macrocycle. The molecular structures of two different salts differ in the square‐pyramidal coordination to the CuII ions. The carboxylate stretching modes, the d‐d and the CT transtitions are not sensitive enough to resolve these differences. The exchange coupling is weakly antiferromagnetic between the CuII ions in the dinuclear subunits and negligible between the subunits via the glutarates. The consequences for suited ligands to model the binding to two neighboring phosphate diesters in the DNA backbone is discussed. [ABSTRACT FROM AUTHOR]

The preparations, photophysical and electrochemical properties of a series of fac‐[Re(CO)3(diimine)Br] complexes are presented. The bipyridine (bpy) based diimine ligands feature symmetrical and asymmetrical 3,3'‐diamino‐2,2'‐bipyridine substitution patterns. Photophysical and electrochemical properties of these complexes are tunable, depending on their organic diimine framework. Introduction of a distal urea bridge via the 3,3'‐substitution pattern led to prolonged phosphorescence lifetimes without a significant change in absorbance and phosphorescence emission wavelengths. Reversible electrochemical bipyridine reduction remained largely unchanged by this derivatization. [ABSTRACT FROM AUTHOR]

Aromatic amines are ubiquitous moieties in organic molecules and their direct functionalization is of great interest in many research areas due to their prevalence in pharmaceuticals and organic electronics. While several synthetic tools exist for the ortho‐ and para‐functionalization of anilines, the functionalization of the less reactive meta‐position is not easy to achieve with current methods. To date, the meta‐C−H arylation of aniline derivatives has been restricted to either the use of directing groups & templates, or their transformation into anilides & quaternary anilinium salts. Herein, we report the first general and efficient meta‐C−H‐arylation of non‐directed aniline derivatives via cooperative catalysis with a palladium–S,O‐ligand–norbornene system. The reaction proceeds under mild conditions with a wide range of aniline derivatives and aryl iodides, while being operationally simple and scalable. Our preliminary mechanistic investigation–including the isolation of several palladium complexes and deuterium experiments–reveal useful insights into the substituent‐effects of both the aniline‐substrate and the norbornene‐mediator during the meta‐C−H activation step. [ABSTRACT FROM AUTHOR]

While still rare, cationic ligands offer much promise as tunable electron‐withdrawing ligands for π‐acid catalysis. Recently, we introduced pincer‐type sulfonium cations into the list of available strongly π‐acidic ancillary ligands. However, the M−S bond in sulfonium complexes of these ligands was found highly labile, precluding their catalytic applications. Herein we demonstrate that this obstacle can be overcome by increasing the rigidity of the sulfonium pincer scaffold. X‐ray analyses confirm that despite bearing a formal positive charge, the sulfur atom of this newly designed sulfonium ligand maintains its coordination to the Pt(II)‐center, while DFT calculations indicate that by doing so it strongly enhances the electrophilic character of the metal. Kinetic studies carried out on three model cycloisomerization reactions prove that such a tris‐cationic sulfonium‐Pt(II) complex is highly reactive, compared to its thioether‐based analogue. This proof‐of‐concept study presents the first example of employing sulfonium‐based ligands in homogeneous catalysis. [ABSTRACT FROM AUTHOR]

The physical and electrochemical properties of a series of Cu complexes bearing redox‐active ligands were investigated. The effect of the geometry and electronic structure on the redox potentials of the CuI/II and ligand‐based oxidation was investigated, in both MeCN and aqueous solutions. Here we found that the formation of a delocalized ligand radical is essential to obtain catalytic activity for water oxidation. Furthermore, we found that ligand‐based oxidation can be controlled by electronic effects of substituent methoxy groups on various positions on the ligand. This allows us to propose design principles for ligands employed in water oxidation catalysts that operate via a SET‐HA mechanism: 1) The redox‐active ligand should contain a negative charge of at least −1 or have the ability to oxidize the ligand via PCET whereby a proton is removed from the ligand. 2) The oxidation potential of the redox‐active ligands can be controlled by introduction of substituents. To decrease this potential, the electron density should be directed at the position of the ligand where oxidation occurs. 3) Stabilization of the oxidized ligand by electronic or delocalization effects decreases the oxidation potential. [ABSTRACT FROM AUTHOR]

The ligand precursor HNacNac‐dibenzofuran‐Br, LH, was synthesized by the condensation of 6‐bromo‐4‐dibenzofuranamine and 4‐(N‐(mesityl)amino)pent‐3‐en‐2‐one with the aim of preparing heterodinuclear nickel/zinc complexes in two successive steps. Reacting LH with Zn(HMDS)2, Zn(C6F5)2 and Zn(C2H5)2 led to the respective X‐Zn‐NacNac‐dibenzofuran‐Br complexes (X=HMDS (2), C6F5 (3), Et (4)). However, in case of 2 and 3 the subsequent treatment with Ni(COD)2/TMEDA did not lead to any conversion, probably as the steric bulk imposed by the NacNac‐Zn‐X entities was too high. 4 did react with Ni(COD)2/TMEDA, likely in the envisaged manner, but apparently the targeted product complex Et‐Zn‐NacNac‐dibenzofuran‐Ni(TMEDA)Br, once formed, immediately reacts further via a Negishi coupling reaction, so that Br‐Zn‐NacNac‐dibenzofuran‐Et (5) is formed. The reaction of 4 with triethylammonium bromide led to the formation of the Br‐Zn‐NacNac‐dibenzofuran‐Br (6) complex that could be reacted with Ni(COD)2/TMEDA successfully. All attempts to purify the product led to Zn(NacNac‐dibenzofuran‐Ni(TMEDA)Br)2, which is insoluble in THF and thus drives a dismutation reaction. [ABSTRACT FROM AUTHOR]

The C═N bond is a critical structural piece of many N-donor ligand scaffolds and is central to the properties and reactivity of important coordination complexes. For example, C═N units play a key role in the "redox non-innocence" of α-diimine complexes and in making charge-transfer excited-state character available to complexes of N-heterocyclic ligands such as bipyridine. In N-heterocycles like pyridine, benzannulation can be used to extend the conjugated C═N-containing π-system to quinoline (2,3-benzopyridine) to acridine (2,3-benzoquinoline). This stabilizes the lowest unoccupied molecular orbital of the molecule and boosts its electron-accepting properties, but the position of the benzannulation matters. For example, phenanthridine (3,4-benzoquinoline), an asymmetric isomer of acridine, bears a similarly electronically accessible extended π-system but with a more chemically isolated "imine-like" C═N moiety. This award paper presents an overview of our work investigating the impact of such site-selective benzannulation on the chemistry and properties of phenanthridine as a molecule and ligand. [ABSTRACT FROM AUTHOR]

Enantioselective reactions that install functional groups at the positions of unactivated C-H bonds can be envisioned to produce intermediates for the synthesis of the active ingredients in pharmaceuticals and agrochemicals directly from simple feedstocks. Among these C-H bond functionalization reactions, those that form carbon-silicon (C-Si) and carbon-boron (C-B) bonds have been pursued because the products of these reactions can be converted to those containing a wide range of functional groups and because compounds containing silicon and boron possess unique properties that can be valuable for medicinal and materials chemistry. Although the silylation and borylation of C-H bonds have undergone extensive development during the past two decades, enantioselective versions of these reactions were not known until a few years ago. In this Minireview, we present the rapid development of enantioselective silylation and borylation of C-H bonds, with an emphasis on the design and development of the types of chiral ligands needed to achieve these reactions and an intention to inspire an expansion of these types of transformations.

To qualify as competent sorbents for airborne contaminants such as iodine vapor, permanent porosity and chemical stability are key criteria for the selection of candidate metal-organic frameworks (MOFs). To ensure these characteristics, in the present study, an unsymmetrical bifunctional ligand incorporating both carboxylic acid and hydroxamic acid groups was employed for MOF [Zn(CBHA)](DMF) [SUM-13; CPHA = 4-carboxyphenylhydroxamate, DMF = N,N-dimethylformamide] design and synthesis. Though coupled with Zn2+, which does not typically yield kinetically robust MOFs with hard acids, the SUM-13 featuring differentiated coordination modes of chelating, bridging and monodentate bonding exhibited exceptional chemical stability and permanent porosity, with a Brunauer–Emmett–Teller (BET) surface area of 296.9 m2/g and a total pore volume of 0.1196 cm3/g. Additionally, with porosity and open metal sites at the five-coordinate Zn2+ centers, SUM-13 was demonstrated to be an eligible iodine adsorbent, reaching a maximum uptake of 796 mg/g. These findings underscore the validity and potential of the design strategy in constructing stable metal–organic frameworks.

The tau-tubulin kinase 1 (TTBK1) protein is a casein kinase 1 superfamily member located at chromosome 6p21.1. It is expressed explicitly in the brain, particularly in the cytoplasm of cortical and hippocampal neurons. TTBK1 has been implicated in the phosphorylation and aggregation of tau in Alzheimer’s disease (AD). Considering its significance in AD, TTBK1 has emerged as a promising target for AD treatment. In the present study, we identified novel TTBK1 inhibitors using various computational techniques. We performed a virtual screening-based docking study followed by E-pharmacophore modeling, cavity-based pharmacophore, and ligand design techniques and found ZINC000095101333, LD7, LD55, and LD75 to be potential novel TTBK1 lead inhibitors. The docking results were complemented by Molecular Mechanics/Generalized Born Surface Area (MMGBSA) calculations. The molecular dynamics (MD) simulation studies at a 500 ns scale were carried out to monitor the behavior of the protein toward the identified ligands. Pharmacological and ADME/T studies were carried out to check the drug-likeness of the compounds. In summary, we identified a new series of compounds that could effectively bind the TTBK1 receptor. The newly designed compounds are promising candidates for developing therapeutics targeting TTBK1 for AD.

Incorporating design elements from homogeneous catalysts to construct well defined active sites on electrode surfaces is a promising approach for developing next generation electrocatalysts for energy conversion reactions. Furthermore, if functionalities that control the electrode microenvironment could be integrated into these active sites it would be particularly appealing. In this context, a square planar nickel calixpyrrole complex, Ni(DPMDA) (DPMDA=2,2′‐((diphenylmethylene)bis(1H‐pyrrole‐5,2‐diyl))bis(methaneylylidene))bis(azaneylylidene))dianiline) with pendant amine groups is reported that forms a heterogeneous hydrogen evolution catalyst using anilinium tetrafluoroborate as the proton source. The supported Ni(DPMDA) catalyst was surprisingly stable and displayed fast reaction kinetics with turnover frequencies (TOF) up to 25,900 s−1 or 366,000 s−1 cm−2. Kinetic isotope effect (KIE) studies revealed a KIE of 5.7, and this data, combined with Tafel slope analysis, suggested that a proton‐coupled electron transfer (PCET) process involving the pendant amine groups was rate‐limiting. While evidence of an outer‐sphere reduction of the Ni(DPMDA) catalyst was observed, it is hypothesized that the control over the secondary coordination sphere provided by the pendant amines facilitated such high TOFs and enabled the PCET mechanism. The results reported herein provide insight into heterogeneous catalyst design and approaches for controlling the secondary coordination sphere on electrode surfaces. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: The design and synthesis of spirochroman‐2‐on‐4,1'‐indan‐7'‐ol (SCIOL) and its application for synthesizing chiral monophosphinite ligands are reported. The synthesis features a tandem double Friedel‐Crafts reaction/lactonization to construct the spiro framework and the desired racemic SCIOL was obtained via 6 steps with a total yield of 44.5%. Using an inclusion resolution with N‐benzylcinchonidinium chloride, the optical SCIOL could be obtained in good yields on a gram scale. The preliminary studies indicated that the corresponding chiral spiro monophosphinite ligands exhibit high catalytic activity and enantioselectivity (up to 94% ee) in the rhodium‐catalyzed asymmetric hydrogenation of N‐acetyl dehydroamino esters. These outcomes highlight the significant potential of SCIOL as a useful framework for the development of chiral spiro ligands. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: The design and synthesis of spirochroman‐2‐on‐4,1'‐indan‐7'‐ol (SCIOL) and its application for synthesizing chiral monophosphinite ligands are reported. The synthesis features a tandem double Friedel‐Crafts reaction/lactonization to construct the spiro framework and the desired racemic SCIOL was obtained via 6 steps with a total yield of 44.5%. Using an inclusion resolution with N‐benzylcinchonidinium chloride, the optical SCIOL could be obtained in good yields on a gram scale. The preliminary studies indicated that the corresponding chiral spiro monophosphinite ligands exhibit high catalytic activity and enantioselectivity (up to 94% ee) in the rhodium‐catalyzed asymmetric hydrogenation of N‐acetyl dehydroamino esters. These outcomes highlight the significant potential of SCIOL as a useful framework for the development of chiral spiro ligands. [ABSTRACT FROM AUTHOR]

With the aim of constructing hydrogen‐bonding networks in synthetic complexes, two new ligands derived from cis,cis‐1,3,5‐triaminocyclohexane (TACH) have been prepared that feature pendant pyrrole or indole rings as outer‐sphere H‐bond donors. The TACH framework offers a facial arrangement of three N‐donors, thereby mimicking common coordination motifs in the active sites of nonheme Fe and Cu enzymes. X‐ray structural characterization of a series of CuI‐X complexes (X=F, Cl, Br, NCS) revealed that these neutral ligands (H3LR, R=pyrrole or indole) coordinate in the intended facial N3 manner, yielding four‐coordinate complexes with idealized C3 symmetry. The N−H units of the outer‐sphere heterocycles form a hydrogen‐bonding cavity around the axial (pseudo)halide ligand, as verified by crystallographic, spectroscopic, and computational analyses. Treatment of H3Lpyrrole and H3Lindole with divalent transition metal chlorides (MIICl2, M=Fe, Cu, Zn) causes one heterocycle to deprotonate and coordinate to the M(II) center, giving rise to tetradentate ligands with two remaining outer‐sphere H‐bond donors. Further ligand deprotonation is observed upon reaction with Ni(II) and Cu(II) salts with weakly coordinating counteranions. The reported complexes highlight the versatility of TACH‐based ligands with pendant H‐bond donors, as the resulting scaffolds can support multiple protonation states, coordination geometries, and H‐bonding interactions. [ABSTRACT FROM AUTHOR]

Herein, a copper(I)‐catalyzed asymmetric hydrophosphination of 3,3‐disubstituted cyclopropenes is reported. It provides a series of phosphine derivatives in high to excellent diastereo‐ and enantioselectivities. The methodology enjoys broad substrate scope on both 3,3‐disubstituted cyclopropenes and diarylphosphines. The high stereoselectivity is attributed to both the high stability of the Cu(I)‐(R,R)‐QUINOXP* complex in the presence of stoichiometric HPPh2 and the produced phosphines, and the high‐performance asymmetric induction of the Cu(I)‐(R,R)‐QUINOXP* complex. Finally, the method is used for the synthesis of new chiral phosphine‐olefin compounds built on a cyclopropane skeleton, one of which serves as a wonderful ligand in Rh‐catalyzed asymmetric conjugate addition of phenylboronic acid to various α,β‐unsaturated compounds. [ABSTRACT FROM AUTHOR]

When designing peptide ligands based on the structure of a protein receptor, it can be very useful to narrow down the possible binding positions and bound conformations of the ligand without the need to choose its amino acid sequence in advance. Here, we construct and benchmark a tool for this purpose based on a recently reported statistical energy model named SCUBA (Sidechain-Unknown Backbone Arrangement) for designing protein backbones without considering specific amino acid sequences. With this tool, backbone fragments of different local conformation types are generated and optimized with SCUBA-driven stochastic simulations and simulated annealing, and then ranked and clustered to obtain representative backbone fragment poses of strong SCUBA interaction energies with the receptor. We computationally benchmarked the tool on 111 known protein-peptide complex structures. When the bound ligands are in the strand conformation, the method is able to generate backbone fragments of both low SCUBA energies and low root mean square deviations from experimental structures of peptide ligands. When the bound ligands are helices or coils, low-energy backbone fragments with binding poses similar to experimental structures have been generated for approximately 50% of benchmark cases. We have examined a number of predicted ligand-receptor complexes by atomistic molecular dynamics simulations, in which the peptide ligands have been found to stay at the predicted binding sites and to maintain their local conformations. These results suggest that promising backbone structures of peptides bound to protein receptors can be designed by identifying outstanding minima on the SCUBA-modeled backbone energy landscape. [ABSTRACT FROM AUTHOR]

A Au‐catalyzed protocol for the enantioselective synthesis of molecular architectures containing an internal [5]helicene and two peripherical axial stereogenic elements is described. While the diasteroselectivity of the double alkyne hydroarylation sequence is not optimal, and mixtures that contain similar amounts of two of the four possible diasteromeric products are obtained (one C2 and one non‐symmetric), the assembly of the C2‐symmetric isomer often occurs with high enantioselectivity (up to 98 % ee). The absolute configurations of the products obtained were determined by X‐ray crystallography. Studies on the thermal racemization of the internal [5]helicene moiety in the C2‐symmetric isomers determined the half‐life of this element to be approximately 3 h at 50 °C. [ABSTRACT FROM AUTHOR]

The outbreak of coronavirus disease 2019 (COVID-19) has sparked an urgent demand for advanced diagnosis and vaccination worldwide. The discovery of high-affinity ligands is of great significance for vaccine and diagnostic reagent manufacturing. Targeting the receptor binding domain (RBD) from the spike protein of severe acute respiratory syndrome-coronavirus 2, an interface at the outer surface of helices on the Z domain from protein A was introduced to construct a virtual library for the screening of ZRBD affibody ligands. Molecular docking was performed using HADDOCK software, and three potential ZRBD affibodies, ZRBD-02, ZRBD-04, and ZRBD-07, were obtained. Molecular dynamics (MD) simulation verified that the binding of ZRBD affibodies to RBD was driven by electrostatic interactions. Per-residue free energy decomposition analysis further substantiated that four residues with negative-charge characteristics on helix α1 of the Z domain participated in this process. Binding affinity analysis by microscale thermophoresis showed that ZRBD affibodies had high affinity for RBD binding, and the lowest dissociation constant was 36.3 nmol/L for ZRBD-07 among the three potential ZRBD affibodies. Herein, ZRBD-02 and ZRBD-07 affibodies were selected for chromatographic verifications after being coupled to thiol-activated Sepharose 6 Fast Flow (SepFF) gel. Chromatographic experiments showed that RBD could bind on both ZRBD SepFF gels and was eluted by 0.1 mol/L NaOH. Moreover, the ZRBD-07 SepFF gel had a higher affinity for RBD. This research provided a new idea for the design of affibody ligands and validated the potential of affibody ligands in the application of RBD purification from complex feedstock. [ABSTRACT FROM AUTHOR]

[Display omitted] Incorporating copper (Cu) ions into polymeric particles can be a straightforward strategy for mimicking copper enzymes, but it is challenging to simultaneously control the structure of the nanozyme and of the active sites. In this report, we present a novel bis-ligand (L 2) containing bipyridine groups connected by a tetra-ethylene oxide (4EO) spacer. In phosphate buffer the Cu-L 2 mixture forms coordination complexes that (at proper composition) can bind polyacrylic acid (PAA) to produce catalytically active polymeric nanoparticles with well-defined structure and size, which we refer to as 'nanozymes'. Manipulating the L 2 /Cu mixing ratio and using phosphate as a co-binding motif, cooperative copper centres are realized that exhibit promoted oxidation activity. The structure and activity of the so-designed nanozymes remain stable upon increasing temperature and over multiple cycles of application. Increasing ionic strength causes enhanced activity, a response also seen for natural tyrosinase. By means of our rational design we obtain nanozymes with optimized structure and active sites that in several respects outperform natural enzymes. This approach therefore demonstrates a novel strategy for developing functional nanozymes, which may well stimulate the application of this class of catalysts. [ABSTRACT FROM AUTHOR]