Musculoskeletal imaging of senescence.

Senescent cells play a vital role in the pathogenesis of musculoskeletal (MSK) diseases, such as chronic inflammatory joint disorders, rheumatoid arthritis (RA), and osteoarthritis (OA). Cellular senescence in articular joints represents a response of local cells to persistent stress that leads to cell-cycle arrest and enhanced production of inflammatory cytokines, which in turn perpetuates joint damage and leads to significant morbidities in afflicted patients. It has been recently discovered that clearance of senescent cells by novel "senolytic" therapies can attenuate the chronic inflammatory microenvironment of RA and OA, preventing further disease progression and supporting healing processes. To identify patients who might benefit from these new senolytic therapies and monitor therapy response, there is an unmet need to identify and map senescent cells in articular joints and related musculoskeletal tissues. To fill this gap, new imaging biomarkers are being developed to detect and characterize senescent cells in human joints and musculoskeletal tissues. This review article will provide an overview of these efforts. New imaging biomarkers for senescence cells are expected to significantly improve the specificity of state-of-the-art imaging technologies for diagnosing musculoskeletal disorders.

Molecular Engineering of Self-Immolative Bioresponsive MR Probes.

Real-time detection of bio-event in whole animals provides essential information for understanding biological and therapeutic processes. Magnetic resonance (MR) imaging represents a non-invasive approach to generating three-dimensional anatomic images with high spatial-temporal resolution and unlimited depth penetration. We have developed several self-immolative enzyme-activatable agents that provide excellent in vivo contrast and function as gene expression reporters. Here, we describe a vast improvement in image contrast over our previous generations of these bioresponsive agents based on a new pyridyl-carbamate Gd(III) complex. The pyridyl-carbamate-based agent has a very low MR relaxivity in the "off-state" (r1 = 1.8 mM-1 s-1 at 1.41 T). However, upon enzymatic processing, it generates a significantly higher relaxivity with a Δr1 = 106% versus Δr1 ∼ 20% reported previously. Single X-ray crystal and nuclear magnetic relaxation dispersion analyses offer mechanistic insights regarding MR signal enhancement at the molecular scale. This work demonstrates a pyridyl-carbamate-based self-immolative molecular platform for the construction of enzymatic bio-responsive MR agents, which can be adapted to a wide range of other targets for exploring stimuli-responsive materials and biomedical applications.

Anthracene-Triphenylamine-Based Platinum(II) Metallacages as Synthetic Light-Harvesting Assembly.

Two trigonal prismatic metallacages 1 and 2 bearing triphenylamine and anthracene moieties are designed and synthesized to fabricate artificial light-harvesting systems (LHSs). These two cages are prepared via the coordination-driven self-assembly of two anthracene-triphenylamine-based tripyridyl ligand 3, three dicarboxylates, and six 90° Pt(II) acceptors. The design of the anthracene-triphenylamine chromophore makes possible the tunable excited-state property (like the emissive transition energy and lifetime) as a function of the solvent polarity, temperature, and concentration. The synergistic photophysical footprint of these metallacages, defined by their high absorptivity and emission quantum yield (QY) relative to the free ligand 3, signifies them as a superior light sensitizer component in an LHS. In the presence of the fluorescent dye Nile Red (NR) as an energy acceptor, the metallacages display efficient (>93%) excited energy transfer to NR through an apparent static quenching mechanism in viscous dimethyl sulfoxide solvent.

Dual-Emissive Tris-Heteroleptic Ruthenium Complexes: Tuning the DNA-Triggered Ratiometric Emission Response by Ancillary Ligands.

Three tris-heteroleptic mononuclear Ru(II) complexes with dual fluorescence and phosphorescence-[Ru(dpma)(bpy)(phen)]2+ (12+), [Ru(dpma)(bpy)(dppz)]2+ (22+), and [Ru(dpma)(phen)(dppz)]2+ (32+)-have been designed and used as ratiometric light-response probes for DNA, where dpma is di(pyrid-2-yl)(methyl)-amine, bpy is 2,2'-bipyridine, phen is 1,10-phenanthroline, and dppz is dipyridophenazine, respectively. Single crystals of complex 2(PF6)2 have been obtained and studied by X-ray analysis. The interactions of these complexes with different DNAs are investigated by means of spectroscopic methods, viscosity measurements, and molecular modeling. In the presence of calf thymus DNA, complexes 2(PF6)2 and 3(PF6)2 show the emergence of a new lower-energy phosphorescence emission band; meanwhile, the higher-energy fluorescence emission band is essentially unchanged, functioning as an intrinsic internal reference. These two complexes exhibit stronger preference for calf thymus DNA over single-strand DNA (d(A)16 and d(C)16). In contrast, no binding interaction between 1(PF6)2 and calf thymus DNA is observed. The intrinsic binding constants (Kb) of 2(PF6)2 and 3(PF6)2 with calf thymus DNA are determined to be (1.4 ± 0.4) × 105 and (9.5 ± 0.15) × 104 M-1, respectively. In addition, these spectroscopic results are compared with those of the prototype complex [Ru(bpy)2(dppz)]2+ (42+), and density functional theory and time-dependent density functional theory calculations are employed to elucidate these experimental findings.

Capture and Release of Singlet Oxygen in Coordination-Driven Self-Assembled Organoplatinum(II) Metallacycles.

Singlet oxygen (1O2), as an important active reagent, has found wide applications in photodynamic therapy (PDT), synthetic chemistry, and materials science. Organic conjugated aromatics serving as hosts to capture and release singlet oxygen have been systematically investigated over the last decades. Herein, we present a [6 + 6] organoplatinum(II) metallacycle by using ∼180° dipyridylanthracene donor and ∼120° Pt(II) acceptor as the building blocks, which enables the capture and release of singlet oxygen with relatively high photooxygenation and thermolysis rate constants. The photooxygenation of the metallacycle to the corresponding endoperoxide was performed by sensitized irradiation, and the resulting endoperoxide is stable at room temperature and can be stored under ambient condition over months. Upon simple heating of the neat endoperoxide under inert atmosphere at 120 °C for 4 h, the resulting endoperoxide can be reconverted to the corresponding parent form and singlet oxygen. The photooxygenation and thermolysis products were characterized by NMR spectroscopy and electrospray ionization time-of-flight mass spectrometric analysis. Density functional theory calculations were conducted in order to reveal the frontier molecular orbital interactions and reactivity. This work provides a new material platform for singlet oxygen related promising applications.

Spontaneous Supramolecular Polymerization Driven by Discrete Platinum Metallacycle-Based Host-Guest Complexation.

Considerable progress in platinum metallacycle-based supramolecular polymerization has promoted the fabrication and application of supramolecular materials. However, despite recent advances, supramolecular polymers constructed through platinum metallacycle-based host-guest complexation remain rare because of the dynamics of platinum metallacycles. Here, we achieve linear supramolecular polymerization via platinum metallacycle-based host-guest complexation by following the design rule of suppressing the dynamics of the metallacycles. The establishment of the platinum metallacycle-based host-guest system and the realization of this type of supramolecular polymerization are expected to open opportunities for platinum metallacycle-based functional materials.

Spontaneous Formation of a Cross-Linked Supramolecular Polymer Both in the Solid State and in Solution, Driven by Platinum(II) Metallacycle-Based Host-Guest Interactions.

The recent progress in platinum(II) coordination-driven supramolecular polymers has had a substantial effect on the design of functional soft materials. However, the prospect of realizing polymerization induced by platinum(II) metallacycle-based host-guest interactions has received little attention until recently. Here we report the realization of supramolecular polymerization driven by platinum(II) metallacycle-based host-guest interactions both in the solid state and in solution. On the basis of the disclosed polymerization mechanism, we present a new strategy for the preparation of platinum(II) metallacycle-based supramolecular polymers.

Metal-Organic Pt(II) Hexagonal-Prism Macrocycles and Their Photophysical Properties.

In this work, we present the formation of two open-ended hexagonal-prism tubular macrocycles by the [6 + 12] self-assembly of the symmetric ∼120° organic ligand donor with ∼90° Pt(II) acceptor in a 1:2 ratio. The assembled structures were characterized by multinuclear NMR (1H NMR, 31P{1H} NMR, and 1H-1H COSY NMR), electrospray ionization mass spectrometry (ESI-TOF-MS), traveling wave ion mobility-mass spectrometry (TWIM-MS), and transmission electron microscopy. Molecular modeling was further conducted to get insight into their structured characteristics. We also examined their photophysical properties.

Molecular Quadripod as a Noncovalent Interfacial Coupling Reagent for Forming Immobilized Coordination Assemblies.

A pyrene-cored molecular quadripod 1,3,6,8-tetra(di( p-pyrid-4-ylphenyl)amino)pyrene (TAPyr) is presented as a noncovalent interfacial coupling reagent for the immobilization of coordination assemblies. This bench-stable molecule is readily available and has a quadripod shape with four pyridine legs and four pyridine handles on the top exterior. By a simple and short dipping procedure under ambient conditions, TAPyr is firmly immobilized on electrode surfaces in an upright fashion as probed by electrochemical, absorption spectral, atomic force microscopy, and scanning tunneling microscopy analysis. Using Pd(PhCN)2Cl2 as a metallolinker, 4-ferrocenylpyridine, a pyridine-terminated monoruthenium complex 1, and a diruthenium complex 2 with two pyridine ends have been grafted onto the ITO/TAPyr surface. The obtained thin films exhibit good electrochemical stability that is comparable or superior to those prepared by the state-of-the-art Si-O-Sn covalent functionalization. Appealing electrochromism is demonstrated with the thin films of ruthenium complexes on ITO.

Temperature-Responsive Fluorescent Organoplatinum(II) Metallacycles.

The synthesis, characterization, and temperature-responsive properties of two fluorescent organoplatinum(II) metallacycles are reported. Metallacycles M1 and M2 were prepared via the coordination-driven self-assembly of a 120° triarylamine ligand L1 and a 120° diplatinum(II) acceptor Pt-1 or 180° diplatinum(II) acceptor Pt-2, respectively. M1 and M2 are hexagonal metallacycles, comprising of three or six freely rotating anthracene pendants on their periphery, respectively. In response to the temperature variation between -20 and 60 °C, the ligand displays irregular emission changes, whereas both metallacycles show reversible absorption and emission spectral changes in THF. The changes in their green emission intensity also exhibit a linear correlation with the temperature variation, with an average sensitivity of -0.67% and -0.77% per °C for M1 and M2, respectively. Furthermore, in coordinating solvents, such as DMF and CH3CN, M1 and M2 show different behaviors: in the lower temperature range, i.e., below 30 °C, their spectral changes are similar to those observed in THF; however, at a higher temperature the metallacycles were presumably destroyed by the solvents and displayed ratiometric fluorescent responses, including a cyan emission of the ligand L1.

Transition from a Metal-Localized Mixed-Valence Compound to a Fully Delocalized and Bridge-Biased Electrophore in a Ruthenium-Amine-Ruthenium Tricenter System.

A series of cyclometalated diruthenium complexes with a redox-active amine bridge were synthesized. Depending on the terminal ligands of the ruthenium components and the substituent on the amine unit, the one-electron-oxidized state can be either in the form of a weakly or strongly coupled mixed-valence diruthenium complex, a fully charge-delocalized three-center system, or a bridge-biased electrophore. This transition among different electronic forms was supported by electrochemistry, near-infrared absorption, electron paramagnetic resonance, and density functional theory analysis.

Ruthenium-Amine Conjugated Organometallic Materials for Multistate Near-IR Electrochromism and Information Storage.

Monometallic and dimetallic complexes with the ruthenium-amine conjugated structural unit have been prepared. These complexes display consecutive redox waves with low potentials and rich and intense absorptions in the near-infrared region. The electrochemical and spectroscopic properties can be modulated using substituents or auxiliary ligands with different electronic natures. Through simple functionalization, electropolymerized or monolayer thin films of these complexes have been prepared. These films display multistate near-infrared electrochromism with good contrast ratios and long optical retention times. In addition, flip-flop and flip-flap-flop memories have been demonstrated on the basis of these thin films.

Observation of the excretion pattern of a precocious line of Eimeria necatrix and the strengthening of immune homogeneity.

The excretion frequencies of cecal and intestinal droppings of Chinese Lingnan yellow chickens were observed for 10 consecutive days. The chickens were then orally inoculated with a precocious line of Eimeria necatrix, and the oocysts present in the cecal and intestinal droppings were separately collected and monitored using the McMaster method. The results showed that the excretion frequency of cecal droppings was significantly lower than that of intestinal droppings, and the oocysts of E. necatrix were distributed primarily in the cecal droppings. This distribution affects the homogeneity of the second and third generation of oocysts ingested by the chickens and therefore affects the immune effect observed during E. necatrix immunization. To artificially strengthen the immunologic homogeneity against E. necatrix, a method of artificially strengthening the second immunization was applied, and the immune effect was evaluated based on oocyst excretion, body weight gain, fecal scores, intestinal lesion scores and survival percentages. The results showed that no significant intestinal damage was caused by immunization reactions in the chickens. In addition, the number of excreted oocysts in the immunized chicken groups could be significantly increased, and the immunologic homogeneity of the immunized chickens could be improved by artificially strengthening the second immunization, which could in turn improve the immune protective effect.

A Molecular Platform for Multistate Near-Infrared Electrochromism and Flip-Flop, Flip-Flap-Flop, and Ternary Memory.

A diruthenium complex with a redox-active amine bridge has been designed, synthesized, and studied by single-crystal X-ray analysis and DFT and TDDFT calculations. It shows three well-separated redox processes with exclusive near-infrared (NIR) absorbance at each redox state. The electropolymerized film of a related vinyl-functionalized complex displays multistate NIR electrochromism with low operational potential, good contrast ratio, and long retention time. Flip-flop, flip-flap-flop, and ternary memories have been realized by using the obtained film (ca. 15-20 nm thick) with three electrochemical inputs and three NIR optical outputs that each displays three levels of signal intensity.

Near-infrared light photocatalysis enabled by a ruthenium complex-integrated metal-organic framework via two-photon absorption.

Photocatalysis under UV/visible light irradiation has emerged as one of the green methodologies for solar energy utilization and organic synthesis. These photocatalytic processes are typically initiated by one-photon-absorbing metal complexes or organic dyes. Nevertheless, the intrinsic restrictions of UV/visible light irradiation, such as shallow penetration in reaction solutions, competing absorption by substrates, and limited coverage of the solar spectrum, call for the development of innovative photocatalysts functioning under longer wavelength irradiation. Herein, we report a ruthenium complex containing a metal-organic framework, MOF-Ru1, which can drive diverse organic reactions under 740 nm light irradiation following the two-photon absorption (TPA) process. Various organic transformations such as energy transfer, reductive, oxidative, and redox neutral reactions were realized using this heterogeneous hybrid photocatalyst. Overall, MOF-Ru1 represents an intriguing TPA photocatalyst active under near-infrared light irradiation, paving a way for the efficient utilization of low-energy light and convenient photocatalyst recycling because of phase separation.

Multidentate Anchors for Surface Functionalization.

The bottom-up functionalization of solid surfaces shows increasing importance for a wide range of interdisciplinary applications. Multidentate anchors with more than two contact points can bind to solid surfaces with strong chemisorption, well-defined upright configuration, and tailored functionality. The surface functionalization using multidentate anchors with three (tripodal), four (quadripodal), or more binding points is summarized herein, with a focus on those beyond classical tripodal anchors. In particular, the molecular design on how to achieve multisite interaction between anchor and substrate and the introduction of functional groups to thin films are discussed.

[Treatment of Piggery Biogas Slurry by Enhanced Biological Contact Oxidation with HN-AD Bacteria].

The conventional pretreatment process for swine wastewater is anaerobic fermentation. This process leads to the formation of high ammonia nitrogen, low carbon, and piggery biogas slurry, which usually results in poor denitrification effect, complicated process flow, and long startup period for the subsequent treatment process. In this study, a novel biological enhanced Biological Contact Oxidation (BCO) process using HN-AD bacteria as microbial inoculants, and PAN activated carbon fiber filler as biofilm carrier was proposed for the treatment of piggery biogas slurry. In the early stage of sludge acclimation, it was found that when NH4+-N concentration was higher than 500 mg·L-1, the nitrification and COD removal in BCO was severely inhibited. When the BCO was enhanced by HN-AD bacteria, however, the tolerance concentration of NH4+-N for bacteria in BCO could reach 600 mg·L-1 and the removal efficiency of NH4+-N, COD, and TN could still remain at a high level. The bio-enhanced BCO process was used to treat the piggery biogas slurry. The average removal rates of NH4+-N, TN, and COD were 86.9%, 70.5%, and 74.4%, respectively, which were higher than the 57.6%, 50.3%, and 50.0% of the traditional treatment process. The concentration of the pollutants mentioned above in the effluent was below the relevant discharge standards. The changes in the microbial community structure during the enrichment process of functional bacteria were studied by high-throughput sequencing technique. The results showed that the dominant bacteria belonging to HN-AD in the biofilm during the sludge acclimation process was Alcaligenes. After the addition of the HN-AD agent, however, the dominant bacteria were Diaphorobacter, Acinetobacter, and Thauer, and the relative abundance of Acinetobacter was much higher than that in the microbial inoculants. The results of scanning electron microscopy further confirmed the existence of bio-enhancement. The surface of the biofilm layer tightly attached to the filler was enriched with rod-like and globular HN-AD functional bacteria.

Single-molecule level control of host-guest interactions in metallocycle-C60 complexes.

Host-guest interactions are of central importance in many biological and chemical processes. However, the investigation of the formation and decomplexation of host-guest systems at the single-molecule level has been a challenging task. Here we show that the single-molecule conductance of organoplatinum(II) metallocycle hosts can be enhanced by an order of magnitude by the incorporation of a C60 guest molecule. Mechanically stretching the metallocycle-C60 junction with a scanning tunneling microscopy break junction technique causes the release of the C60 guest from the metallocycle, and consequently the conductance switches back to the free-host level. Metallocycle hosts with different shapes and cavity sizes show different degrees of flexibility to accommodate the C60 guest in response to mechanical stretching. DFT calculations provide further insights into the electronic structures and charge transport properties of the molecular junctions based on metallocycles and the metallocycle-C60 complexes.

Resistive memory devices based on a triphenylamine-decorated non-precious cobalt(ii) bis-terpyridine complex.

The ITO/active material/Au sandwiched devices of a cobalt(ii) bis-terpyridine complex decorated with two triphenylamine motifs display appealing flash-type resistive switching with a large ON/OFF ratio (>103) and low operating voltages (<±3 V). In contrast, devices with the triphenylamine-appended terpyridine ligand show WORM-type memory behaviour.

Multistate Redox Switching and Near-Infrared Electrochromism Based on a Star-Shaped Triruthenium Complex with a Triarylamine Core.

A star-shaped cyclometalated triruthenium complex 2(PF6)n (n = 3 and 4) with a triarylamine core was synthesized, which functions as a molecular switch with five well-separated redox states in both solution and film states. The single-crystal X-ray structure of 2(PF6)3 is presented. This complex displays four consecutive one-electron redox waves at +0.082, +0.31, +0.74, and +1.07 V vs Ag/AgCl. In each redox state, it shows significantly different NIR absorptions with λmax of 1590 nm for 24+, 1400 nm for 25+, 1060 nm for 26+, and 740 nm for 27+, respectively. Complex 24+ shows a single-line EPR signal at g = 2.060, while other redox states are all EPR inactive. The spin density distributions and NIR absorptions in different redox states were rationalized by DFT and TDDFT calculations. A vinyl-substituted triruthenium analogous 3(PF6)4 was prepared, which was successfully polymerized on ITO glass electrode surfaces by reductive electropolymerization. The obtained poly-3n+/ITO film was characterized by FTIR, AFM, and SEM analysis. It shows four well-defined redox couples and reversible multistate NIR electrochromism. In particular, a contrast ratio (ΔT%) up to 63% was achieved at the optic telecommunication wavelength (1550 nm).