Donor and Ring-Fusing Engineering for Far-Red to Near-Infrared Triphenylpyrylium Fluorophores with Enhanced Fluorescence Performance for Sensing and Imaging.

Fluorescent probes have become an indispensable tool in the detection and imaging of biological and disease-related analytes due to their sensitivity and technical simplicity. In particular, fluorescent probes with far-red to near-infrared (FR-NIR) emissions are very attractive for biomedical applications. However, many available FR-NIR fluorophores suffer from small Stokes shifts and sometimes low quantum yields, resulting in self-quenching and low contrast. In this work, we describe the rational design and engineering of FR-NIR 2,4,6-triphenylpyrylium-based fluorophores (TPP-Fluors) with the help of theoretical calculations. Our strategy is based on the appending of electron-donating substituents and fusing groups onto 2,4,6-triphenylpyrylium. In contrast to the parent TPP with short emission wavelength, weak quantum yields, and low chemical stability, the obtained novel TPP-Fluors display some favorable properties, such as long-wavelength emission, large Stokes shifts, moderate to high quantum yields, and chemical stability. TPP-Fluors demonstrate their biological value as mitochondria-specific labeling reagents due to their inherently positive nature. In addition, TPP-Fluors can also be applied to develop ratiometric fluorescent probes, as the electron-donating ability of the 2,6-phenyl substituents is closely correlated with their emission wavelength. A proof-of-concept ratiometric probe has been developed by derivatizing the amino groups of TPP-Fluor for the detection and imaging of nitroreductase in vitro and in hypoxic cells.

Enhancing the Anti-Solvatochromic Two-Photon Fluorescence for Cirrhosis Imaging by Forming a Hydrogen-Bond Network.

Two-photon imaging is an emerging tool for biomedical research and clinical diagnostics. Electron donor-acceptor (D-A) type molecules are the most widely employed two-photon scaffolds. However, current D-A type fluorophores suffer from solvatochromic quenching in aqueous biological samples. To address this issue, we devised a novel class of D-A type green fluorescent protein (GFP) chromophore analogues that form a hydrogen-bond network in water to improve the two-photon efficiency. Our design results in two-photon chalcone (TPC) dyes with 0.80 quantum yield and large two-photon action cross section (210 GM) in water. This strategy to form hydrogen bonds can be generalized to design two-photon materials with anti-solvatochromic fluorescence. To demonstrate the improved in vivo imaging, we designed a sulfide probe based on TPC dyes and monitored endogenous H2 S generation and scavenging in the cirrhotic rat liver for the first time.

A Multifunctional Nanozyme with NADH Dehydrogenase-Like Activity and Nitric Oxide Release under Near-Infrared Light Irradiation as an Efficient Therapeutic for Antimicrobial Resistance Infection and Wound Healing.

In recent years, antimicrobial resistance (AMR) has become one of the greatest threats to human health. There is an urgent need to develop new antibacterial agents to effectively treat AMR infection. Herein, a novel nanozyme platform (Cu,N-GQDs@Ru-NO) is prepared, where Cu,N-doped graphene quantum dots (Cu,N-GQDs) are covalently functionalized with a nitric oxide (NO) donor, ruthenium nitrosyl (Ru-NO). Under 808 nm near-infrared (NIR) light irradiation, Cu,N-GQDs@Ru-NO demonstrates nicotinamide adenine dinucleotide (NADH) dehydrogenase-like activity for photo-oxidizing NADH to NAD+ , thus disrupting the redox balance in bacterial cells and resulting in bacterial death; meanwhile, the onsite NIR light-delivered NO effectively eradicates the methicillin-resistant Staphylococcus aureus (MRSA) bacterial and biofilms, and promotes wound healing; furthermore, the nanozyme shows excellent photothermal effect that enhances the antibacterial efficacy as well. With the combination of NADH dehydrogenase activity, photothermal therapy, and NO gas therapy, the Cu,N-GQDs@Ru-NO nanozyme displays both in vitro and in vivo excellent efficacy for MRSA infection and biofilm eradication, which provides a new therapeutic modality for effectively treating MRSA inflammatory wounds.

Cellular membrane-targeting ruthenium complexes as efficient photosensitizers for broad-spectrum antibacterial activity.

A ruthenium complex [Ru(phen)2(phen-5-amine)-C14] (Ru-C14) with broad-spectrum antibacterial activity was designed and synthesized; positively charged Ru-C14 could target bacteria via electrostatic interactions and showed high binding effectiveness to cell membranes. In addition, Ru-C14 could act as a photosensitizer. Under 465 nm light irradiation, Ru-C14 could generate 1O2, thus disrupting the bacterial intracellular redox balance and leading to bacterial death. Ru-C14 also exhibited minimum inhibitory concentration values of 6.25 µM against Escherichia coli and 3.125 µM against Staphylococcus aureus; these values are lower than those of streptomycin and methicillin. This work combined the merits of cell membrane targeting and photodynamic therapy for antibacterial activity. The findings might open up a new avenue for effective anti-infection treatment and other medical applications.

A Ruthenium Nitrosyl-Functionalized Magnetic Nanoplatform with Near-Infrared Light-Controlled Nitric Oxide Delivery and Photothermal Effect for Enhanced Antitumor and Antibacterial Therapy.

Developing a spatiotemporal-controlled nitric oxide (NO) delivery nanoplatform is highly desirable for its biological applications as a tumor inhibitor and antibacterial agent. In this study, a novel multifunctional magnetic nanoplatform {Fe3O4@PDA@Ru-NO@FA} (1) was developed for the near-infrared (NIR) light-controlled release of NO in which a ruthenium nitrosyl (Ru-NO) donor and a folic acid (FA)-directing group were covalently functionalized onto Fe3O4@PDA. Nanoplatform 1 preferentially accumulated in folate receptor-overexpressing cancer cell lines and magnetic field-guided tumor tissue, instantly released NO, and simultaneously produced a prominent photothermal effect upon 808 nm NIR light irradiation, leading to remarkable in vitro and in vivo antitumor efficacy. When nanoplatform 1 was treated only once, the potential MRI contrast agent was sufficient to significantly inhibit or eliminate the tumor tissues in living mice, thus offering opportunities for future NO-involved multimodal cancer therapy. In addition, a NO delivery nanoplatform {Fe3O4@PDA@Ru-NO} was imbedded in the matrix of a chitosan (CS)-poly(vinyl alcohol) (PVA) material to develop a hybrid thermosensitive CS-PVA/NO hydrogel. The CS-PVA/NO hydrogels demonstrated mild (<150 mW cm-2) NIR light-controlled NO delivery and thus produced an efficient antibacterial effect for both Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus. Therefore, these hydrogels have potential as antibacterial dressings for wound bacterial infection treatment.

Targeted and NIR light-controlled delivery of nitric oxide combined with a platinum(iv) prodrug for enhanced anticancer therapy.

This study reports a strategy of combining a Pt(iv) prodrug and a ruthenium nitrosyl (Ru-NO) donor into a single nanoplatform {N-GQDs@Ru-NO-Pt@FA} in which the platinum(iv) prodrug is conjugated onto a photoactivatable NO donor (Ru-NO) through a covalent bond and the nitric oxide-releasing platinum prodrug and folate groups are decorated on N-doped graphene quantum dots (N-GQDs). After cellular uptake of the nanoplatform, the platinum(iv) prodrug was reduced to an active anti-cancer Pt(ii) species inside the cancerous cells, and simultaneously, near-infrared (NIR) light illumination induced the release of NO, accompanied by a prominent photothermal effect. This nanoplatform is capable of targeting intracellular co-delivery of Pt(ii) and NO under 808 nm NIR light irradiation, accompanied by photothermal therapy, thereby leading to a significant synergistic therapeutic effect.

Detection of analytes in mitochondria without interference from other sites based on an innovative ratiometric fluorophore.

Mitochondria are vital organelles that not only produce cellular energy but also participate in many biological processes. Recently, various fluorescent probes have been developed for mitochondrial imaging. However, due to the lack of suitable dyes or strategies, it is difficult for most reported mitochondrial targeting probes to prove whether the analytes they detected are from mitochondria. In addition, positive charge on mitochondrial probes can seriously affect the mitochondrial environment. To address these issues, we herein put forward a novel strategy for probe design based on a smart NIR dye (HDFL) for mitochondrial targeting detection. Compared to general mitochondrial targeting probes that are modified with a target site and a reaction site, the new strategy is to combine the two sites together for a mitochondrial probe that would provide accurate detection of analytes in mitochondria without interference. As a proof of concept, we synthesized a mitochondrial-targetable probe HDFL-Cys for cysteine. Bioimaging studies have shown that the new type of probe HDFL-Cys can first accumulate in mitochondria and then react with the analyte (cysteine) accompanied by the departure of the targeting group (lipophilic cation moieties). Thus, it can specifically detect the analyte in mitochondria without interference from extra-mitochondrial analytes. We anticipate that the new strategy based on the novel NIR dye HDFL may be a potential platform for developing desirable ratiometric fluorescent probes for mitochondrial imaging.

Platinum/nitrogen-doped carbon/carbon cloth: a bifunctional catalyst for the electrochemical reduction and carboxylation of CO2 with excellent efficiency.

A novel Pt-NP@NCNF@CC composite was prepared by the electrospinning technique. It is a highly efficient and binder-free catalyst for the direct reduction and carboxylation of CO2 with halides. Formate with 91% Faradaic efficiency and 2-phenylpropionic acid with 99% yield could be obtained, respectively. Moreover, this catalyst has excellent stability and reusability.

A Core-Shell-Structured Silver Nanowire/Nitrogen-Doped Carbon Catalyst for Enhanced and Multifunctional Electrofixation of CO2.

Numerous catalysts have been successfully introduced for CO2 fixation in aqueous or organic systems. However, a single catalyst showing activity in both solvent types is still rare, to the best of our knowledge. We developed a core-shell-structured AgNW/NC700 composite using a Ag nanowire (NW) core encapsulated by a N-doped carbon (NC) shell at 700 °C. Through control experiments and density functional theory calculations, it was confirmed that Ag nanowires acted as the active sites for CO2 fixation and the uniformly coating of N-doped carbon created a CO2 -rich environment around the Ag nanowires, which could significantly improve the catalytic activity of Ag nanowires for electrochemical CO2 fixation. Under mild conditions, up to 96 % faradaic efficiency of CO, 95 % yield of Ibuprofen and 92 % yield of propylene carbonate could be obtained in the electrochemical CO2 direct reduction, carboxylation and cycloaddition, respectively, using the same AgNWs/NC700 catalyst. These results might provide an alternative strategy for efficient electrochemical fixation of CO2 .

A ruthenium-nitrosyl-functionalized nanoplatform for the targeting of liver cancer cells and NIR-light-controlled delivery of nitric oxide combined with photothermal therapy.

The development of light-controlled nitric oxide (NO)-releasing nanoplatforms that are capable of specifically targeting liver cancer cell lines and delivering an optimal amount of NO can significantly affect liver cancer therapy. In this study, a multifunctional nanoplatform {N-GQDs@Ru-NO@Gal} (1) for the near-infrared (NIR) light-responsive release of NO, consisting of a NO donor (Ru-NO) and a liver-targeting galactose derivative (Gal) covalently attached to N-doped graphene quantum dots (N-GQDs), was reported. Nanoplatform 1 preferentially targeted liver cancer cells over normal cells and instantly released NO as well as exhibited a prominent photothermal effect upon NIR irradiation at 808 nm, thereby leading to efficient anti-tumor efficacy. {N-GQDs@Ru-NO@Gal} with a small size (<10 nm), good biocompatibility, and fluorescent-tracing properties represents a unique example of a multifunctional NO-releasing nanoplatform that combines photodynamic and photothermal therapies for the targeted treatment of liver cancer. Hence, the developed nanoplatform demonstrates potential for applications in NO-mediated multimodal phototherapy in the near future.

Efficient electrocatalytic O2 reduction at copper complexes grafted onto polyvinylimidazole coated carbon nanotubes.

A facile approach to prepare Cu complexes for an efficient oxygen reduction reaction (ORR) was developed. Copper complexes of 5-nitrophenanthroline were sandwiched between polyvinylimidazole layers wrapped on carbon nanotubes, which showed ORR activity comparable to a Pt/C catalyst in alkaline media.

Ruthenium nitrosyl functionalized graphene quantum dots as an efficient nanoplatform for NIR-light-controlled and mitochondria-targeted delivery of nitric oxide combined with photothermal therapy.

A mitochondria-targeting nanoplatform for near-infrared-light-controlled release of nitric oxide accompanied by photothermal therapy was developed, which consists of ruthenium nitrosyl functionalized N-doped graphene quantum dots and a triphenylphosphonium moiety. The nanoplatform demonstrated both in vitro and in vivo anti-tumor efficacy upon irradiation with 808 nm light.

A multifunctional nanoplatform for lysosome targeted delivery of nitric oxide and photothermal therapy under 808 nm near-infrared light.

Nitric oxide (NO) plays important roles in various physiological and pathological processes. The development of multifunctional nanoplatforms that enable site-specific delivery of NO is expected to provide new insights toward the realization of NO-mediated therapy. We report herein a novel nanoplatform {Lyso-Ru-NO@FA@CDs}, (1), where a lysosome-targeting NO donor, Lyso-Ru-NO, and a folic-acid (FA)-directing group were incorporated into carbon dots (CDs). Nanoplatform 1 exhibited immediate NO release and a rapid temperature increase when irradiated using an 808 nm laser. This nanoplatform was capable of targeting folate-receptor-positive cancer cell lines and specifically accumulated in the subcellular lysosomal organelle. The dual-targeted nanoplatform 1 exhibited high cytotoxicity toward cancer cells under irradiation with 808 nm light, demonstrating substantially enhanced efficacy compared with its nontargeted counterparts. NIR-light-controlled spatiotemporal delivery of NO to targeted sites accompanied by photothermal therapy offers new possibilities for NO-involved multimodal cancer treatment.

Ruthenium nitrosyl grafted carbon dots as a fluorescence-trackable nanoplatform for visible light-controlled nitric oxide release and targeted intracellular delivery.

Nitric oxide (NO) plays a key role in various physiological and pathological processes. It is of great significance in developing a platform that enables exogenous delivery of NO spatiotemporally to a targeted site for realizing NO-mediated therapy. We report herein a stable, multifunctional NO-delivery nanoplatform that is capable of target directing, fluorescence tracking, and light-controlled NO delivery. A ruthenium nitrosyl [Ru(TPYCOOH)(o-phenylenediamine)(NO)](PF6)3 and a target-directing molecule of folic acid (FA) were covalently grafted onto the surface of a carrier of carbon dots (CDs), forming a {Ru-NO@FA@CDs} nanoplatform. This nanoplatform is fluorescence self-trackable in a cellular environment and can recognize specific cancer cells via FA-folate receptor binding; it was selectively taken up by cancer cells to enter the cytosol, in which localized NO was produced on demand by adept control of visible light illumination. This offered the potential for treating diseases derived from NO deficiency as well as NO-mediated cancer therapy.

DNA-binding and photoactivated enantiospecific cleavage of chiral polypyridyl ruthenium(II) complexes.

A series of enantiomeric polypyridyl ruthenium(II) complexes Delta- and Lambda-[Ru(bpy)2CNOIP](PF6)2 (Delta-1 and Lambda-1; BPY=2,2'-bipyridine, CNOIP=2-(2-chloro-5-nitrophenyl)imidazo[4,5-f][1,10]phenanthroline), Delta- and Lambda-[Ru(bpy)2HPIP](PF6)2 (Delta-2 and Lambda-2; HPIP=2-(2-hydroxyphenyl)imidazo[4,5-f][1,10]phenanthroline), Delta- and Lambda-[Ru(bpy)2DPPZ](PF6)2 (Delta-3 and Lambda-3; DPPZ=dipyrido[3,2:a-2',3':c]-phenazine), Delta- and Lambda-[Ru(bpy)2TAPTP](PF6)2 (Delta-4 and Lambda-4; TAPTP=4,5,9,18-tetraazaphenanthreno[9,10-b] triphenylene) have been synthesized. Binding of these chiral complexes to calf thymus DNA has been studied by spectroscopic methods, viscosity, and equilibrium dialysis. The experimental results indicated that all the enantiomers of these complexes bound to DNA through an intercalative mode, but the binding affinity of each chiral complex to DNA was different due to the different shape and planarity of the intercalative ligand. After binding to DNA, the luminescence property of complex 1 was distinctly different from complexes 2 to 4. Upon irradiation at 302 nm, complexes 2-4 were found to promote the cleavage of plasmid pBR 322 DNA from supercoiled form I to nicked form II, and obvious enantioselectively was observed on DNA cleavage for the enantiomers of complexes 2 and 4. The mechanisms for DNA cleavage by these enantiomeric complexes were also proposed.

A functionalized cobalt(III) mixed-polypyridyl complex as a newly designed DNA molecular light switch.

The ligand ODHIP (3,4-dihydroxyl-imidazo[4,5-f][1,10]phenanthroline) and its cobalt(III) complex [Co(bpy)(2)(ODHIP)](3+) were synthesized and characterized. Binding of this complex with calf thymus DNA has been investigated by spectroscopic methods and viscosity. The experimental results indicated that the complex bound to DNA by intercalation. In Tris buffer, the complex could emit relatively weak luminescence. After binding to DNA, the notable enhancement was observed. However, when the Cu(2+) was further added, the luminescence decreased gradually and disappeared after the equimolar concentrations of Cu(2+) was added, which exhibited the "off-on-off" properties of molecular light switch.

Screening and mutagenesis of Aspergillus niger for the improvement of glucose 6-phosphate dehydrogenase production.

The strain of Aspergillus niger ZBY-7 was selected as the original strain of glucose 6-phosphate dehydrogenase production. After mutagenesis of the strain using UV irradiation and nitrosoguanidine, mutants of Aspergillus niger resistant to certain metabolic inhibitor were obtained. Five of the mutants showed increased glucose 6-phosphate dehydrogenase production. The mutant resistant to antimycin A (Aspergillus niger AM-23) produced the highest level of glucose 6-phosphate dehydrogenase (695.9% of that from the original strain).