Cryo-ET of Env on intact HIV virions reveals structural variation and positioning on the Gag lattice.

HIV-1 Env mediates viral entry into host cells and is the sole target for neutralizing antibodies. However, Env structure and organization in its native virion context has eluded detailed characterization. Here, we used cryo-electron tomography to analyze Env in mature and immature HIV-1 particles. Immature particles showed distinct Env positioning relative to the underlying Gag lattice, providing insights into long-standing questions about Env incorporation. A 9.1-Å sub-tomogram-averaged reconstruction of virion-bound Env in conjunction with structural mass spectrometry revealed unexpected features, including a variable central core of the gp41 subunit, heterogeneous glycosylation between protomers, and a flexible stalk that allows Env tilting and variable exposure of neutralizing epitopes. Together, our results provide an integrative understanding of HIV assembly and structural variation in Env antigen presentation.

Long-distance tmFRET using bipyridyl- and phenanthroline-based ligands.

With the great progress on determining protein structures over the last decade comes a renewed appreciation that structures must be combined with dynamics and energetics to understand function. Fluorescence spectroscopy, specifically Förster resonance energy transfer (FRET), provides a great window into dynamics and energetics due to its application at physiological temperatures and ability to measure dynamics on the ångström scale. We have recently advanced transition metal FRET (tmFRET) to study allosteric regulation of maltose binding protein and have reported measurements of maltose-dependent distance changes with an accuracy of ∼1.5 Å. When paired with the noncanonical amino acid Acd as a donor, our previous tmFRET acceptors were useful over a working distance of 10 to 20 Å. Here, we use cysteine-reactive bipyridyl and phenanthroline compounds as chelators for Fe2+ and Ru2+ to produce novel tmFRET acceptors to expand the working distance to as long as 50 Å, while preserving our ability to resolve even small maltose-dependent changes in distance. We compare our measured FRET efficiencies to predictions based on models using rotameric ensembles of the donors and acceptors to demonstrate that steady-state measurements of tmFRET with our new probes have unprecedented ability to measure conformational rearrangements under physiological conditions.

A Molecular Hybrid of the GFP Chromophore and 2,2'-Bipyridine: An Accessible Sensor for Zn2+ Detection with Fluorescence Microscopy.

The few commercially available chemosensors and published probes for in vitro Zn2+ detection in two-photon microscopy are compromised by their flawed spectroscopic properties, causing issues in selectivity or challenging multistep syntheses. Herein, we present the development of an effective small molecular GFP chromophore-based fluorescent chemosensor with a 2,2'-bipyridine chelator moiety (GFZnP BIPY) for Zn2+ detection that has straightforward synthesis and uncompromised properties. Detailed experimental characterizations of the free and the zinc-bound compounds within the physiologically relevant pH range are presented. Excellent photophysical characteristics are reported, including a 53-fold fluorescence enhancement with excitation and emission maxima at 422 nm and 492 nm, respectively. A high two-photon cross section of 3.0 GM at 840 nm as well as excellent metal ion selectivity are reported. In vitro experiments on HEK 293 cell culture were carried out using two-photon microscopy to demonstrate the applicability of the novel sensor for zinc bioimaging.

Imaging of Single Bacteria with Electrochemiluminescence Microscopy.

Rapid and accurate identification of pathogens is crucial for public healthcare and patient treatment. However, the commonly used analytic tools such as molecular diagnostics and mass spectrometry are either expensive or have long turnaround times for sample purification and amplification. Here, we introduce electrochemiluminescence (ECL) microscopy with a high spatiotemporal resolution and a unique chemical contrast to image and identify single bacteria. Direct bacterial counting and classification with an accuracy of up to 90.5% is demonstrated. We further report a novel tunable ECL imaging mode which can switch from the negative contrast ECL imaging without labeling to positive contrast ECL imaging with adsorption of tris(2,2'-bipyridyl) ruthenium(II) for bacterial imaging. With this contrast tuning effect, single-molecule ECL microscopy is employed for imaging the microscopic structures of single bacteria. This work shows that ECL microscopy can offer a powerful quantitative imaging methodology with chemical information for bacterial characterization.

Binding and stabilizating effect of RNA triplex poly(U)⋠poly(A)*poly(U) by enantiomers of ruthenium(II) polypyridyl complex [Ru(bpy)2(dppx)]2.

Two chiral ruthenium(II) polypyridyl complexes, Λ-[Ru(bpy)2(dppx)]2+ (bpy = 2,2'-bipyridine, dppx = 7,8-dimethyldipyridophenazine; Λ-1) and Δ-[Ru(bpy)2(dppx)]2+ (Δ-1) have been synthesized and characterized in this work. Interactions of Λ-1 and Δ-1 with the RNA triplex poly(U)⋅poly(A)*poly(U) have been investigated by various biophysical techniques. Spectrophotometric titrations and viscosity measurements suggested that enantiomers Λ-1 and Δ-1 bind with the triplex through intercalation, while the binding strengths of the two enantiomers toward the triplex differed only slightly from each other. Fluorescence titrations showed that although enantiomers Λ-1 and Δ-1 exhibited molecular "light switch" effects toward the triplex, the effect of Δ-1 was more marked. Furthermore, Furthermore, thermal denaturation showed that the two enantiomers have significantly different stabilizing effects on the triplex. The obtained results indicate that the racemic complex [Ru(bpy)2(dppx)]2+ is similar to a non-specific metallointercalator for the triplex investigated in this study, and chiralities of Ru(II) polypyridine complexes have an important influence on the binding and stabilizing effects of enantiomers toward the triplex. Two chiral ruthenium(II) polypyridyl complexes, Λ-[Ru(bpy)2(dppx)]2+ (bpy = 2,2'-bipyridine, dppx = 7,8-dimethyldipyridophenazine; Λ-1) and Δ-[Ru(bpy)2(dppx)]2+ (Δ-1) have been synthesized and characterized in this work. Interactions of Λ-1 and Δ-1 with the RNA triplex poly(U)⋅poly(A)*poly(U) have been investigated by various biophysical techniques. The obtained results indicate that the racemic complex [Ru(bpy)2(dppx)]2+ is similar as a non-specific metallointercalator for the triplex investigated in this study, and chiralities of Ru(II) polypyridine complexes have an important influence on the binding and stabilizing effects of enantiomers toward the triplex.

Cyanine-Functionalized 2,2'-Bipyridine Compounds for Photocatalytic Cancer Therapy.

Recently, interest has been given to developing photocatalytic anticancer drugs. This area of research is dominated by metal complexes. Here, we report the potential of lysosome/mitochondria targeting cyanine appended bipyridine compounds as the organic photocatalytic anticancer agents. The organocatalyst (bpyPCN) not only exhibits light-induced NADH oxidation but also generates intracellular ROS to demonstrate anticancer activity. This is the first example of organic compound induced catalytic NADH photo-oxidation in an aqueous solution and in cancer cells.

Design and Synthesis of Poly(2,2'-Bipyridyl) Ligands for Induction of Cell Death in Cancer Cells: Control of Anticancer Activity by Complexation/Decomplexation with Biorelevant Metal Cations.

Chelation therapy is a medical procedure for removing toxic metals from human organs and tissues and for the treatment of diseases by using metal-chelating agents. For example, iron chelation therapy is designed not only for the treatment of metal poisoning but also for some diseases that are induced by iron overload, cancer chemotherapy, and related diseases. However, the use of such metal chelators needs to be generally carried out very carefully, because of the side effects possibly due to the non-specific complexation with intracellular metal cations. Herein, we report on the preparation and characterization of some new poly(bpy) ligands (bpy: 2,2'-bipyridyl) that contain one-three bpy ligand moieties and their anticancer activity against Jurkat, MOLT-4, U937, HeLa S3, and A549 cell lines. The results of MTT assays revealed that the tris(bpy) and bis(bpy) ligands exhibit potent activity for inducing the cell death in cancer cells. Mechanistic studies suggest that the main pathway responsible for the cell death by these poly(bpy) ligands is apoptotic cell death. It was also found that the anticancer activity of the poly(bpy) ligands could be controlled by the complexation (anticancer activity is turned OFF) and decomplexation (anticancer activity is turned ON) with biorelevant metal cations. In this paper, these results will be described.

Triarylphosphine-Coordinated Bipyridyl Ru(II) Complexes Induce Mitochondrial Dysfunction.

While cancer cells rely heavily upon glycolysis to meet their energetic needs, reducing the importance of mitochondrial oxidative respiration processes, more recent studies have shown that their mitochondria still play an active role in the bioenergetics of metastases. This feature, in combination with the regulatory role of mitochondria in cell death, has made this organelle an attractive anticancer target. Here, we report the synthesis and biological characterization of triarylphosphine-containing bipyridyl ruthenium (Ru(II)) compounds and found distinct differences as a function of the substituents on the bipyridine and phosphine ligands. 4,4'-Dimethylbipyridyl-substituted compound 3 exhibited especially high depolarizing capabilities, and this depolarization was selective for the mitochondrial membrane and occurred within minutes of treatment in cancer cells. The Ru(II) complex 3 exhibited an 8-fold increase in depolarized mitochondrial membranes, as determined by flow cytometry, which compares favorably to the 2-fold increase observed by carbonyl cyanide chlorophenylhydrazone (CCCP), a proton ionophore that shuttles protons across membranes, depositing them into the mitochondrial matrix. Fluorination of the triphenylphosphine ligand provided a scaffold that maintained potency against a range of cancer cells but avoided inducing toxicity in zebrafish embryos at higher concentrations, displaying the potential of these Ru(II) compounds for anticancer applications. This study provides essential information regarding the role of ancillary ligands for the anticancer activity of Ru(II) coordination compounds that induce mitochondrial dysfunction.

[AuIII(N

A series of new complexes of general formula [AuIII(N^N)Br2](PF6) (N^N = 2,2'-bipyridine and 1,10-phenanthroline derivatives) were prepared and characterized by spectroscopic, electrochemical, and diffractometric techniques and tested against Gram-positive and Gram-negative bacterial strains (Staphylococcus aureus, Streptococcus intermedius, Pseudomonas aeruginosa, and Escherichia coli), showing promising antibacterial and antibiofilm properties.

Liquid-assisted mechanochemical synthesis, crystallographic, theoretical and molecular docking study on HIV instasome of novel copper complexes: (µ-acetato)-bis(2,2'-bipyridine)-copper and bromidotetrakis(2-methyl-1H-imidazole)-copper bromide.

In the present work the two new Cu(II) complexes, (µ-acetato)-bis(2,2'-bipyridine)-copper [Cu(bpy)2(CH3CO2)] and bromidotetrakis(2-methyl-1H-imidazole)-copper bromide [Cu(2-methylimid)4Br]Br have been synthesized by liquid assisted mechanochemical method. The [Cu(bpy)2(CH3CO2)] complex (1) and [Cu(2-methylimid)4Br]Br complex (2) characterised by IR and UV-visible spectroscopy and the structure are confirmed by XRD diffraction studies. Complex (1) crystallized in the Monoclinic with the space group of C2/c where a = 24.312(5) Å, b = 8.5892(18) Å, c = 14.559(3) Å, α = 90°, ß = 106.177(7)° and γ = 90° and Complex (2) crystallized in the Tetragonal with the space group of P4nc, a = 9.9259(2) Å, b = 9.9259(2) Å, c = 10.9357(2) Å, α = 90°, ß = 90° and γ = 90°. The complex (1) has distorted octahedral geometry where the acetate ligand showed bidentate bridging with the central metal ion and complex (2) has slightly deformed square pyramidal geometry. The HOMO-LUMO energy gap value and the low chemical potential showed that the complex (2) is stable and difficult to polarize compare to complex (1). The molecular docking study of complexes with the HIV instasome nucleoprotein showed the binding energy values - 7.1 and - 5.3 kcal/mol for complex (1) and complex (2) respectively. The negative binding energy values showed the complexes have affinity to bind with HIV instasome nucleoproteins. The in-silico pharmacokinetic study of the complex (1) and complex (2) showed non AMES toxicity, non-carcinogens and low honey Bee toxicity but weakly inhibit Human Ether-a-go-go-related gene.

Orellanine: From Fungal Origin to a Potential Future Cancer Treatment.

Fungal metabolites represent an underutilized resource in the development of novel anticancer drugs. This review will focus on the promising fungal nephrotoxin orellanine, found in mushrooms including Cortinarius orellanus (Fools webcap). Emphasis will be placed on its historical significance, structural features, and associated toxicomechanics. Chromatographic methods for analysis of the compound and its metabolites, its synthesis, and chemotherapeutic potential are also discussed. Although orellanine's exceptional selectivity for proximal tubular cells is well documented, the mechanics of its toxicity in kidney tissue remains disputed. Here, the most commonly proposed hypotheses are detailed in the context of the molecule's structure, the symptoms seen following ingestion, and its characteristic prolonged latency period. Chromatographic analysis of orellanine and its related substances remains challenging, while biological evaluation of the compound is complicated by uncertainty regarding the role of active metabolites. This has limited efforts to structurally refine the molecule; despite numerous established methods for its synthesis, there is minimal published material on how orellanine's structure might be optimized for therapeutic use. Despite these obstacles, orellanine has generated promising data in preclinical studies of metastatic clear cell renal cell carcinoma, leading to the early 2022 announcement of phase I/II trials in humans.

Determination of pioglitazone hydrochloride by flow injection chemiluminescence tris(2,2'-bipyridyl)ruthenium(II)-silver(III) complex system.

A novel flow injection-chemiluminescence (FI-CL) approach is proposed for the assay of pioglitazone hydrochloride (PG-HCl) based on its enhancing influence on the tris(2,2'-bipyridyl)ruthenium(II)-silver(III) complex (Ru(bipy)3 2+ -DPA) CL system in sulfuric acid medium. The possible CL reaction mechanism is discussed with CL and ultraviolet (UV) spectra. The optimum experimental conditions were found as: Ru(bipy)3 2+ , 5.0 × 10-5  M; sulfuric acid, 1.0 × 10-3  M; diperiodatoargentate(III) (DPA), 1.0 × 10-4  M; potassium hydroxide, 1.0 × 10-3  M; flow rate 4.0 ml min-1 for each flow stream and sample loop volume, 180 µl. The CL intensity of PG-HCl was linear in the range of 1.0 × 10-3 to 5.0 mg L-1 (R2 = 0.9998, n = 10) with limit of detection [LOD, signal-to-noise ratio (S/N) = 3] of 2.2 × 10-4  mg L-1 , limit of quantification (LOQ, S/N = 10) of 6.7 × 10-4  mg L-1 , relative standard deviation (RSD) of 1.0 to 3.3% and sampling rate of 106 h-1 . The methodology was satisfactorily used to quantify PG-HCl in pharmaceutical tablets with recoveries ranging from 93.17 to 102.77 and RSD from 1.9 to 2.8%.

Ruthenium polypyridine complexes containing prenyl groups as antibacterial agents against Staphylococcus aureus through a membrane-disruption mechanism.

Four new ruthenium polypyridyl complexes with prenyl groups, [Ru(bpy)2 (MHIP)](PF6 )2 (Ru(II)-1), [Ru(dtb)2 (MHIP)](PF6 )2 (Ru(II)-2), [Ru(dmb)2 (MHIP)](PF6 )2 (Ru(II)-3), and [Ru(dmob)2 (MHIP)](PF6 )2 (Ru(II)-4) (bpy = 2,2'-bipyridine, dtb = 4,4'-di-tert-butyl-2,2'-bipyridine, dmb = 4,4'-dimethyl-2,2'-bipyridine, dmob = 4,4'-dimethoxy-2,2'-bipyridine, and MHIP = 2-(2,6-dimethylhepta-1,5-dien-1-yl)-1H-imidazo[4,f][1,10]phenanthroline), were synthesized and characterized. Their antibacterial activities against Staphylococcus aureus were assessed, and the minimum inhibition concentration (MIC) value of Ru(II)-2 against S. aureus was only 0.5 µg/mL, showing the best antibacterial activity among them. S. aureus could be quickly killed by Ru(II)-2 in 30 min and Ru(II)-2 displayed an obvious inhibitive effect on the formation of a biofilm, which was essential to avoid the development of drug-resistance. Meanwhile, Ru(II)-2 exhibited a stable MIC value against antibiotic-resistant bacteria. The antibacterial mechanism of Ru(II)-2 was probably related to depolarization of the cell membrane, and a change of permeability was associated with the formation of reactive oxygen species, leading to leakage of nucleic acid and bacterial death. Furthermore, Ru(II)-2 hardly showed toxicity to mammalian cells and the Galleria mellonella worm. Finally, murine infection studies also illustrated that Ru(II)-2 was highly effective against S. aureus in vivo.

Weak, Broken, but Working-Intramolecular Hydrogen Bond in 2,2'-bipyridine.

From an academic and practical point of view, it is desirable to be able to assess the possibility of the proton exchange of a given molecular system just by knowing the positions of the proton acceptor and the proton donor. This study addresses the difference between intramolecular hydrogen bonds in 2,2'-bipyridinium and 1,10-phenanthrolinium. Solid-state 15N NMR and model calculations show that these hydrogen bonds are weak; their energies are 25 kJ/mol and 15 kJ/mol, respectively. Neither these hydrogen bonds nor N-H stretches can be responsible for the fast reversible proton transfer observed for 2,2'-bipyridinium in a polar solvent down to 115 K. This process must have been caused by an external force, which was a fluctuating electric field present in the solution. However, these hydrogen bonds are the grain that tips the scales precisely because they are an integral part of a large system of interactions, including both intramolecular interactions and environmental influence.

Effective and Selective Ru(II)-Arene Complexes Containing 4,4'-Substituted 2,2' Bipyridine Ligands Targeting Human Urinary Bladder Cancer Cells.

Cisplatin-based chemotherapy is a common regimen for bladder cancer, a life-threatening cancer with more than 500,000 new cases worldwide annually. Like many other metallodrugs, cisplatin causes severe side effects for its general toxicity. Organoruthenium is known for its structural stability, good anticancer activity, and possible low general toxicity. Here, we have prepared and characterized a series of water-soluble ruthenium-arene complexes with N,N'-chelating ligands: [Ru(II)-η6-arene-(4,4'-(X)2-2,2'-bipyridine)Cl]Cl (arene = p-cymene, X = C4H9 (1), COOH (2), COOCH3 (3), COOC2H5 (4); arene = benzene, X = C4H9 (5), COOCH3 (6), COOC2H5 (7)). These complexes are carefully characterized using single-crystal X-ray diffraction, UV-vis, IR, 1H NMR, and MALDI-TOF MS spectroscopy. Their DFT-calculated structural and thermodynamic properties are consistent with the experimental observations. Biophysicochemical studies of complex interaction with CTDNA and BSA supported by molecular docking simulations reveal suitable properties of 1-7 as anticancer agents. Cytotoxicities of 1-7 are evaluated on healthy human MCF-10a-breast epithelial and African green monkey Vero cells, and carcinoma human HepG-2-hepatic, T24-bladder, and EAhy-926-endothelial cells. All complexes exhibit much higher cytotoxicity for T24 than cisplatin. Particularly, 1 and 2 are also highly selective toward T24. Fluorescence imaging and flow cytometry demonstrate that 1 and 2 penetrate T24 cell membrane and induce early apoptosis at their respective IC50 concentrations, which ultimately lead to cell death. Statistical analysis suggests that the order of importance for T24 cell antiproliferation is protein binding, Log p, Ru-Cl bond length, while DNA binding is the least important. This study is the first to report the anti-bladder cancer efficacy of Ru-arene-2,2'-bipyridine complexes, and may provide insights for rational design of organoruthenium drugs in the enduring search for new chemotherapeutic agents.

Dichloro(2,2'-bipyridine)copper/MAO: An Active and Stereospecific Catalyst for 1,3-Diene Polymerization.

Dichloro(2,2'-bipyridine)copper was synthesized by reacting copper dichloride with bypyridine, and its behavior, in combination with methylaluminoxane (MAO), in the polymerization of butadiene, isoprene, 2,3-dimethyl-1,3 butadiene, and 3-methyl-1,3-pentadiene was examined. The purpose of this study is to find catalytic systems that are more sustainable than those currently used for the polymerization of butadiene and isoprene (e.g., Co and Ni), but that are comparable in terms of catalytic activity and selectivity. Predominantly, syndiotactic 1,2 polybutadiene, crystalline syndiotactic 3,4 polyisoprene, crystalline syndiotactic 1,2 poly(3-methyl-1,3-pentadiene), and crystalline cis-1,4 poly(2,3-dimethyl-1,3-butadiene) were obtained in a manner similar to that observed with the analogous iron complex. As far as we know, the investigated catalytic system represents the first example of a copper-based catalyst in the field of stereospecific polymerization. Given the great availability of copper, its extremely low toxicity (and therefore high sustainability), and the similarity of its behavior to that of iron, the result obtained seems to us of considerable interest and worthy of further investigation.

Rhenium(I) Block Copolymers Based on Polyvinylpyrrolidone: A Successful Strategy to Water-Solubility and Biocompatibility.

A series of diphosphine Re(I) complexes Re1-Re4 have been designed via decoration of the archetypal core {Re(CO)2(N^N)} through the installations of the phosphines P0 and P1 bearing the terminal double bond, where N^N = 2,2'-bipyridine (N^N1), 4,4'-di-tert-butyl-2,2'-bipyridine (N^N2) or 2,9-dimethyl-1,10-phenanthroline (N^N3) and P0 = diphenylvinylphosphine, and P1 = 4-(diphenylphosphino)styrene. These complexes were copolymerized with the corresponding N-vinylpyrrolidone-based Macro-RAFT agents of different polymer chain lengths to give water-soluble copolymers of low-molecular p(VP-l-Re) and high-molecular p(VP-h-Re) block-copolymers containing rhenium complexes. Compounds Re1-Re4, as well as the copolymers p(VP-l-Re) and p(VP-h-Re), demonstrate phosphorescence from a 3MLCT excited state typical for this type of chromophores. The copolymers p(VP-l-Re#) and p(VP-h-Re#) display weak sensitivity to molecular oxygen in aqueous and buffered media, which becomes almost negligible in the model physiological media. In cell experiments with CHO-K1 cell line, p(VP-l-Re2) and p(VP-h-Re2) displayed significantly reduced toxicity compared to the initial Re2 complex and internalized into cells presumably by endocytic pathways, being eventually accumulated in endosomes. The sensitivity of the copolymers to oxygen examined in CHO-K1 cells via phosphorescence lifetime imaging microscopy (PLIM) proved to be inessential.

Electrochemiluminescence Distance and Reactivity of Coreactants Determine the Sensitivity of Bead-Based Immunoassays.

Herein we report the study of electrochemiluminescence (ECL) generation by tris(2,2'-bipyridyl)ruthenium (Ru(bpy)3 2+ ) and five tertiary amine coreactants. The ECL distance and lifetime of coreactant radical cations were measured by ECL self-interference spectroscopy. And the reactivity of coreactants was quantitatively evaluated in terms of integrated ECL intensity. By statistical analysis of ECL images of single Ru(bpy)3 2+ -labeled microbeads, we propose that ECL distance and reactivity of coreactant codetermine the emission intensity and thus the sensitivity of immunoassay. 2,2-bis(hydroxymethyl)-2,2',2''-nitrilotriethanol (BIS-TRIS) can well balance ECL distance-reactivity trade-off and enhance the sensitivity by 236 % compared with tri-n-propylamine (TPrA) in the bead-based immunoassay of carcinoembryonic antigen. The study brings an insightful understanding of ECL generation in bead-based immunoassay and a way of maximizing the analytical sensitivity from the aspect of coreactant.

Correlating Thermodynamic and Kinetic Hydricities of Rhenium Hydrides.

The kinetics of hydride transfer from Re(Rbpy)(CO)3H (bpy = 4,4'-R-2,2'-bipyridine; R = OMe, tBu, Me, H, Br, COOMe, CF3) to CO2 and seven different cationic N-heterocycles were determined. Additionally, the thermodynamic hydricities of complexes of the type Re(Rbpy)(CO)3H were established primarily using computational methods. Linear free-energy relationships (LFERs) derived by correlating thermodynamic and kinetic hydricities indicate that, in general, the rate of hydride transfer increases as the thermodynamic driving force for the reaction increases. Kinetic isotope effects range from inverse for hydride transfer reactions with a small driving force to normal for reactions with a large driving force. Hammett analysis indicates that hydride transfer reactions with greater thermodynamic driving force are less sensitive to changes in the electronic properties of the metal hydride, presumably because there is less buildup of charge in the increasingly early transition state. Bronsted α values were obtained for a range of hydride transfer reactions and along with DFT calculations suggest the reactions are concerted, which enables the use of Marcus theory to analyze hydride transfer reactions involving transition metal hydrides. It is notable, however, that even slight perturbations in the steric properties of the Re hydride or the hydride acceptor result in large deviations in the predicted rate of hydride transfer based on thermodynamic driving forces. This indicates that thermodynamic considerations alone cannot be used to predict the rate of hydride transfer, which has implications for catalyst design.

Taming Tris(bipyridine)ruthenium(II) and Its Reactions in Water by Capture/Release with Shape-Switchable Symmetry-Matched Cyclophanes.

Electron/proton transfers in water proceeding from ground/excited states are the elementary reactions of chemistry. These reactions of an iconic class of molecules─polypyridineRu(II)─are now controlled by capturing or releasing three of them with hosts that are shape-switchable. Reversible erection or collapse of the host walls allows such switchability. Some reaction rates are suppressed by factors of up to 120 by inclusive binding of the metal complexes. This puts nanometric coordination chemistry in a box that can be open or shut as necessary. Such second-sphere complexation can allow considerable control to be exerted on photocatalysis, electrocatalysis, and luminescent sensing involving polypyridineRu(II) compounds. The capturing states of hosts are symmetry-matched to guests for selective binding and display submicromolar affinities. A perching complex, which is an intermediate state between capturing and releasing states, is also demonstrated.