ABSTRACT
Nature has endowed us with some complex enzymes capable of utilizing proteins as their substrates to generate functional proteins through post-translational modification. However, nanozymes' interplay with proteins as substrates is scarce, with their chemistry predominantly established using only small molecule substrates, featuring a significant gap in this area. Due to the huge prospects of nanozymes in biotechnological and therapeutic interventions, studies establishing the unexplored roles of nanozymes in the biological environments and their interplay beyond small molecule substrates warrant immediate attention. In this study, we unveil the unprecedented role of a Mn-based oxidase nanozyme (MnN) in activating a structural protein, collagen, and covalently crosslinking its tyrosine residues with only a trace amount of tannic acid (TA) without compromising its triple-helical structural integrity. While therapeutic applications demand materials prepared from collagen, the current chemical and physical crosslinking of collagen often presents significant challenges such as toxicity, denaturation, or high costs. MnN lucidly accomplishes crosslinking interplay at its 101 facets using oxygen as a co-substrate under mild conditions. This process takes advantage of MnN being active at mild acidic pH where collagen preferentially exists as a soluble triple helix (monomeric form), exposing functionalities and enhancing the crosslinking degree. Importantly, this reaction also confers 100% resistance to collagenase attack on the collagen tendon-derived biological material. The catalyzed TA-tyrosine linkage in the telopeptide region of collagen probably impedes the initial recognition step of collagenase, providing robust protection against its degradative action. Our study not only expands the repertoire of nanozymes' substrates beyond the existing library of small molecules but also establishes a significant step toward designing a gold standard for collagen crosslinking. With biomedical applications demanding biomaterials derived from protein scaffolds with preserved structural integrity, our investigation bridges the gap between nanozymes' chemistry and crosslinking proteins, opening exciting prospects for biomaterial development.
ABSTRACT
Advances in nanozymes have taken shape over the past few years in several domains. However, persisting challenging limitations of selectivity, specificity, and efficiency necessitate careful attention to aid in the development of next-generation artificial enzymes. Despite nanozymes having significant therapeutic and biotechnological prospects, the multienzyme mimetic activities can compromise their intended applications. Furthermore, the lack of substrate selectivity can hamper crucial biological pathways. While working on addressing the challenges of nanozymes, in this work, we aim to highlight the interplay between the substrates and bis-(µ-oxo) dicopper active site-installed MOF-808 for selectively mimicking oxidase. This oxidase mimetic with a small pore-aperture (1.4 nm), similar to the opening of enzyme binding pockets, projects a tight control over the dynamics and the reactivity of substrates, making it distinct from the general oxidase nanozymes. Interestingly, the design and the well-regulated activity of this nanozyme effectively thwart DNA from approaching the active site, thereby preventing its oxidative damage. Crucially, we also show that despite these merits, the oxidase selectivity is compromised by small proteins such as cytochrome c (Cyt c), having dimensions larger than the pore aperture of MOF-808. This reaction lucidly produces water molecules as a result of four electron transfer to an oxygen molecule. Such unintended side reactivities warrant special attention as they can perturb redox processes and several cellular energy pathways. Through this study, we provide a close look at designing next-generation artificial enzymes that can address the complex challenges for their utility in advanced applications.
ABSTRACT
Reactive oxygen species (ROS) refer to various partially reduced oxygen moieties that are naturally generated due to biochemical processes. Elevated formation of ROS leads to damage to biomolecules, resulting in oxidative stress and cell death. The increased level of ROS also affects therapeutics based on stem cell transplantation. Nanomaterials-based enzyme mimetics have attracted immense attention, but there are several challenges to be addressed in terms of selectivity, efficiency, and biocompatibility. This highlight focuses on a recent investigation by Cheng and coworkers, who engineered an Mn-superoxide dismutase (Mn-SOD)-inspired material with Mn-N5 sites having an axial ligand and 2D d-π-conjugated network. This engineering approach enhances antioxidase-like function and effectively rescues stem cells from ROS. In addition, it also protects osteogenesis-related gene transcription, ensuring survival rates and osteogenic differentiation of hMSCs under ROS environment. This versatile and robust artificial antioxidase holds promise for stem cell therapies and ROS-originated diseases.
Subject(s)
Cytoprotection , Osteogenesis , Reactive Oxygen Species/metabolism , Ligands , Oxidative Stress , Superoxide Dismutase/metabolismABSTRACT
The evolution of cancers to resist existing therapeutic strategies has constantly led researchers to design next-generation therapeutics. Research on nanomedicine holds significant potential in developing newer cancer therapeutics. Nanozymes bearing the properties of enzymes can be promising anticancer agents due to their tunable enzyme-like properties. In one such approach, a biocompatible cobalt-single-atom nanozyme (Co-SAs@NC) bearing catalase and oxidase-like activities that function in cascade at the tumor microenvironment has been reported recently. The current highlight discusses this investigation to unveil Co-SAs@NC's mechanism in tumor cell apoptosis through inâ vivo studies.
Subject(s)
Neoplasms , Tumor Microenvironment , Humans , Neoplasms/drug therapy , CatalysisABSTRACT
The outbreak of coronavirus disease 2019 (COVID-19) has adversely affected the public domain causing unprecedented cases and high mortality across the globe. This has brought back the concept of biosafety into the spotlight to solve biosafety problems in developing diagnostics and therapeutics to treat COVID-19. The advances in nanotechnology and material science in combination with medicinal chemistry have provided a new perspective to overcome this crisis. Herein, we discuss the efforts of researchers in the field of material science in developing personal protective equipment (PPE), detection devices, vaccines, drug delivery systems, and medical equipment. Such a synergistic approach of disciplines can strengthen the research to develop biosafety products in solving biosafety problems.
ABSTRACT
Organoselenium chemistry has emerged as a distinctive area of research with tremendous utility in the synthesis of biologically and pharmaceutically active molecules. Significant synthetic approaches have been made for the construction of C-Se bonds, which are useful in other organic transformations. This review focuses on the versatility of transition metal-mediated selenylation reactions, providing insights into various synthetic pathways and mechanistic details. Furthermore, this review aims to offer a broad perspective for designing efficient and novel catalysts to incorporate organoselenium moiety into the inert C-H bonds.
Subject(s)
Transition Elements , Catalysis , Transition Elements/chemistryABSTRACT
Antimicrobial resistance has long been viewed as a lethal threat to global health. Despite the availability of a wide range of antibacterial medicines all around the world, organisms have evolved a resistance mechanism to these therapies. As a result, a scenario has emerged requiring the development of effective antibacterial drugs/agents. In this article, we exclusively highlight a significant finding reported by Zboril and associates (Adv. Sci. 2021, 2003090). The authors construct a covalently bounded silver-cyanographene (GCN/Ag) with the antibacterial activity of 30 fold higher than that of free Ag ions or typical Ag nanoparticles (AgNPs). Ascribed to the strong covalent bond between nitrile and Ag, an immense cytocompatibility is shown by the GCN/Ag towards healthy human cells with a minute leaching of Ag ions. Firm interactions between the microbial membrane and the GCN/Ag are confirmed by molecular dynamics simulations, which rule out the dependence of antibacterial activity upon the Ag ions alone. Thus, this study furnishes ample scope to unfold next-generation hybrid antimicrobial drugs to confront infections arising from drug and Ag-resistant bacterial strains.
Subject(s)
Anti-Bacterial Agents/pharmacology , Bacteria/drug effects , Metal Nanoparticles/chemistry , Nitriles/pharmacology , Silver/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/toxicity , Drug Resistance, Bacterial/drug effects , Graphite/chemistry , Graphite/pharmacology , Graphite/toxicity , Metal Nanoparticles/toxicity , Microbial Sensitivity Tests , Nitriles/chemistry , Nitriles/toxicity , Silver/chemistry , Silver/toxicityABSTRACT
The extensive use of plastic and the absence of efficient and sustainable methods for its degradation has raised critical concerns about its disposal and degradation. Furthermore, the escalated use of personal protective equipment (PPE) and masks during the ongoing COVID-19 pandemic has put us under tremendous pressure of generating huge amounts of plastic waste. Traditional plastic waste disintegration protocols, while effective, pose additional inevitable environmental risks. Owing to this, almost all the used plastic is directly discarded into the marine and terrestrial bodies, causing great harm to the flora and fauna. Plastic has even started entering the food chain in the form of micro- and nano-plastics, leading to deleterious effects. Considering the global need for finding sustainable ways to degrade plastic, several approaches have been developed. Herein we highlight and rationally compare the recent reports on the development of benign alternatives for the sustainable disintegration of plastic detritus into value-added products. Here we discuss, in depth, photoreforming of a variety of polymers to liquid fuels under natural conditions; enzyme-based deconstruction of polymeric materials via microorganisms and their engineered mutants into useful virgin monomers at ambient temperature; and pyrocatalytic degradation of polyethylene through efficient synthetic materials into valuable fuels and waxes. By critically analyzing the methods, we also provide our opinion on such sustainable techniques and discuss newer approaches related to bioinspired and biomimetic chemistry principles for the management of plastic waste.
Subject(s)
Environmental Pollutants/chemistry , Plastics/chemistry , Polymers/chemistry , Sustainable Development , Waste Management/methods , Biodegradation, Environmental , HumansABSTRACT
The infamous COVID-19 outbreak has left a crippling impact on the economy, healthcare infrastructure, and lives of the general working class, with all the scientists determined to find suitable and efficient diagnostic techniques and therapies to contain its ramifications. This article presents the complete outline of the diagnostic platforms developed using nanoparticles in the detection of SARS-CoV-2, delineating the direct and indirect use of nanomaterials in COVID-19 diagnosis. The properties of nanostructured materials and their relevance in the development of novel point-of-care diagnostic approaches for COVID-19 are highlighted. More importantly, the advantages of nanotechnologies over conventional reverse transcriptase-polymerase chain reaction technique and few other methods used in the detection of SARS-CoV-2 along with the viewpoints are discussed. Also, the future perspectives highlighting the commercial aspects of the nanotechnology-based diagnostic tools developed to combat the COVID-19 pandemic are presented.
Subject(s)
COVID-19/diagnosis , Nanostructures/chemistry , Point-of-Care Testing , Antibodies, Viral/analysis , Antibodies, Viral/chemistry , Biosensing Techniques/methods , COVID-19/virology , Colorimetry , Humans , Nucleic Acid Amplification Techniques , RNA, Viral/analysis , RNA, Viral/chemistry , SARS-CoV-2/genetics , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purificationABSTRACT
Developing robust methods to detect the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a causative agent for the current global health pandemic, is an exciting area of research. Nevertheless, the currently used conventional reverse transcription-polymerase chain reaction (RT-PCR) technique in COVID-19 detection endures with some inevitable limitations. Consequently, the establishment of rapid diagnostic tools and quick isolation of infected patients is highly essential. Furthermore, the requirement of point-of-care testing is the need of the hour. Considering this, we have provided a brief review of the use of very recently reported robust spectral tools for rapid COVID-19 detection. The spectral tools include, colorimetric reverse transcription loop-mediated isothermal amplification (RT-LAMP) and matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), with the admittance of principal component analysis (PCA) and machine learning (ML) for meeting the high-throughput and fool-proof platforms for the detection of SARS-CoV-2, are reviewed. Recently, these techniques have been readily applied to screen a large number of suspected patients within a short period and they demonstrated higher sensitivity for the detection of COVID-19 patients from unaffected human subjects.
ABSTRACT
Gold (Au) has emerged as a superior element, because of its widespread applications in electronic and medical fields. The desirable physical, chemical, optical, and inherent enzyme-like properties of Au are efficiently exploited for detection, diagnostic, and therapeutic purposes. Au offers a unique advantage of fabricating gold nanostructures (GNS) having exact physical, chemical, optical, and enzyme-like properties required for the specific biomedical application. In this Review, the emerging trend of GNS for various biomedical applications is highlighted. Some notable structural and chemical modifications achieved for the detection of biomolecules, pathogens, diagnosis of diseases, and therapeutic applications are discussed in brief. The limitations of GNS during biomedical usage are highlighted and the way forward to overcome these limitations are discussed.
Subject(s)
Gold , Nanostructures , Gold/therapeutic use , Nanostructures/therapeutic useABSTRACT
Efficient loading of drugs in novel delivery agents has the potential to substantially improve therapy by targeting the diseased tissue while avoiding unwanted side effects. Here we report the first systematic study of the loading mechanism of phenanthriplatin and its analogs into tobacco mosaic virus (TMV), previously used by our group as an efficient carrier for anticancer drug delivery. A detailed investigation of the preferential uptake of phenanthriplatin in its aquated form (â¼2000 molecules per TMV particle versus â¼1000 for the chlorido form) is provided. Whereas the net charge of phenanthriplatin analogs and their ionic mobilities have no effect on loading, the reactivity of aqua phenanthriplatin with the glutamates, lining the interior walls of the channel of TMV, has a pronounced effect on its loading. MALDI-MS analysis along with NMR spectroscopic studies of a model reaction of hydroxy-phenanthriplatin with acetate establish the formation of stable covalent adducts. The increased number of heteroaromatic rings on the platinum ligand appears to enhance loading, possibly by stabilizing hydrophobic stacking interactions with TMV core components, specifically Pro102 and Thr103 residues neighboring Glu97 and Glu106 in the channel. Electron transfer dissociation MS/MS fragmentation, a technique that can prevent mass-condition-vulnerable modification of proteins, reveals that Glu97 preferentially participates over Glu106 in covalent bond formation to the platinum center.
Subject(s)
Organoplatinum Compounds/chemistry , Phenanthridines/chemistry , Tobacco Mosaic Virus/chemistry , Models, Molecular , Molecular Structure , Organoplatinum Compounds/metabolism , Phenanthridines/metabolism , Tobacco Mosaic Virus/metabolismABSTRACT
Nano-sized titanium dioxide photocatalysts were synthesized by hybrid hydrolytic nonhydrolytic sol-gel method using aliphatic organic acid templates to study the effect of chain length on their properties. X-ray diffraction pattern indicated crystalline anatase phase. The Barrett-Joyner-Halenda surface area measurement gave surface area ranging from 98.4 to 205.5m(2)/g and was found to be dependent on the chain length of the aliphatic acid. The longer chain acids rendered the material with high surface area. The organic acids acted as bidentate ligand and a surfactant in controlling the size and the mesoporosity. The size of the TiO2 nanoparticulate was found to be in the range of 10-18nm. The catalyst prepared by employing long chain acids octanoic acid and palmitic acid had smaller size, narrow pore radius, higher surface area and showed better photocatalytic activity than the commercially available Degussa P25 catalyst for the degradation of methylene blue dye. A new intermediate was identified by tandem liquid chromatography mass spectrometry studies during the degradation of methylene blue solution.
ABSTRACT
Nanomaterials-based enzyme mimetics (nanozymes) have attracted considerable interest due to their applications in imaging, diagnostics, and therapeutic treatments. Particularly, metal-oxide nanozymes have been shown to mimic the interesting redox properties and biological activities of metalloenzymes. Here we describe an efficient synthesis of MnFe2 O4 nanomaterials and show how the morphology can be controlled by using a simple co-precipitation method. The nanomaterials prepared by this method exhibit a remarkable oxidase-like activity. Interestingly, the activity is morphology-dependent, with nanooctahedra (NOh) exhibiting a catalytic efficiency of 2.21×10(9) m(-1) s(-1) , the highest activity ever reported for a nanozyme.
Subject(s)
Iron/metabolism , Manganese/metabolism , Nanostructures/chemistry , Oxidoreductases/metabolism , Oxygen/metabolism , Iron/chemistry , Manganese/chemistry , Oxidoreductases/chemistry , Oxygen/chemistry , Particle Size , Surface PropertiesABSTRACT
Organophosphorus-based nerve agents, such as paraoxon, parathion, and malathion, inhibit acetylcholinesterase, which results in paralysis, respiratory failure, and death. Bacteria are known to use the enzyme phosphotriesterase (PTE) to break down these compounds. In this work, we designed vacancy-engineered nanoceria (VE CeO2 NPs) as PTE mimetic hotspots for the rapid degradation of nerve agents. We observed that the hydrolytic effect of the nanomaterial is due to the synergistic activity between both Ce(3+) and Ce(4+) ions located in the active site-like hotspots. Furthermore, the catalysis by nanoceria overcomes the product inhibition generally observed for PTE and small molecule-based PTE mimetics.
Subject(s)
Cerium/chemistry , Enzymes/metabolism , Molecular Mimicry , Nerve Agents/metabolism , Organophosphorus Compounds/metabolism , Biodegradation, Environmental , Microscopy, Electron, Transmission , X-Ray DiffractionABSTRACT
Nanomaterials with enzyme-like properties has attracted significant interest, although limited information is available on their biological activities in cells. Here we show that V2O5 nanowires (Vn) functionally mimic the antioxidant enzyme glutathione peroxidase by using cellular glutathione. Although bulk V2O5 is known to be toxic to the cells, the property is altered when converted into a nanomaterial form. The Vn nanozymes readily internalize into mammalian cells of multiple origin (kidney, neuronal, prostate, cervical) and exhibit robust enzyme-like activity by scavenging the reactive oxygen species when challenged against intrinsic and extrinsic oxidative stress. The Vn nanozymes fully restore the redox balance without perturbing the cellular antioxidant defense, thus providing an important cytoprotection for biomolecules against harmful oxidative damage. Based on our findings, we envision that biocompatible Vn nanowires can provide future therapeutic potential to prevent ageing, cardiac disorders and several neurological conditions, including Parkinson's and Alzheimer's disease.
Subject(s)
Antioxidants/metabolism , Nanowires/chemistry , Protective Agents/metabolism , Vanadates/metabolism , Antioxidants/chemistry , Cytoprotection , Glutathione/metabolism , Glutathione Disulfide/metabolism , Glutathione Peroxidase/metabolism , HEK293 Cells , Humans , Oxidation-Reduction , Protective Agents/chemistry , Reactive Oxygen Species/metabolism , Vanadates/chemistryABSTRACT
A catalytic reduction of graphene oxide (GO) by glutathione peroxidase (GPx) mimics is reported. This study reveals that GO contains peroxide functionalities, in addition to the epoxy, hydroxyl and carboxylic acid groups that have been identified earlier. It also is shown that GO acts as a peroxide substrate in the GPx-like catalytic activity of organoselenium/tellurium compounds. The reaction of tellurol, generated from the corresponding ditelluride, reduces GO through the glutathione (GSH)-mediated cleavage of the peroxide linkage. The mechanism of GO reduction by the tellurol in the presence of GSH involves the formation of a tellurenic acid and tellurenyl sulfide intermediates. Interestingly, the GPx mimics also catalyze the decarboxylation of the carboxylic acid functionality in GO at ambient conditions. Whereas the selenium/tellurium-mediated catalytic reduction/decarboxylation of GO may find applications in bioremediation processes, this study suggests that the modification of GO by biologically relevant compounds such as redox proteins must be taken into account when using GO for biomedical applications because such modifications can alter the fundamental properties of GO.
Subject(s)
Biomimetic Materials/chemistry , Glutathione Peroxidase/chemistry , Graphite/chemistry , Nanostructures/chemistry , Organoselenium Compounds/chemistry , Oxides/chemistry , Tellurium/chemistry , Catalysis , Oxidation-ReductionABSTRACT
Facile and efficient reduction of graphene oxide (GO) and novel applications of the reduced graphene oxide (RGO) based materials are of current interest. Herein, we report a novel and facile method for the reduction of GO by using a biocompatible reducing agent dithiothreitol (DTT). Stabilization of DTT by the formation of a six-membered ring with internal disulfide linkage upon oxidation is responsible for the reduction of GO. The reduced graphene oxide is characterized by several spectroscopic and microscopic techniques. Dispersion of RGO in DMF remained stable for several weeks suggesting that the RGO obtained by DTT-mediated reduction is hydrophobic in nature. This method can be considered for large scale production of good quality RGO. Treatment of RGO with hemin afforded a functional hemin-reduced graphene oxide (H-RGO) hybrid material that exhibited remarkable protective effects against the potentially harmful peroxynitrite (PN). A detailed inhibition study on PN-mediated oxidation and nitration reactions indicate that the interaction between hemin and RGO results in a synergistic effect, which leads to an efficient reduction of PN to nitrate. The RGO also catalyzes the isomerization of PN to nitrate as the RGO layers facilitate the rapid recombination of (·)NO(2) with Fe(IV)=O species. In the presence of reducing agents such as ascorbic acid, the Fe(IV)=O species can be reduced to Fe(III), thus helping to maintain the PN reductase cycle.
Subject(s)
Graphite/chemistry , Hemin/chemistry , Nanoshells/chemistry , Oxides/chemistry , Peroxynitrous Acid/chemistry , Oxidation-Reduction , Particle Size , Stereoisomerism , Surface PropertiesABSTRACT
In this study, ebselen and its analogues are shown to be catalysts for the decomposition of peroxynitrite (PN). This study suggests that the PN-scavenging ability of selenenyl amides can be enhanced by a suitable substitution at the phenyl ring in ebselen. Detailed mechanistic studies on the reactivity of ebselen and its analogues towards PN reveal that these compounds react directly with PN to generate highly unstable selenoxides that undergo a rapid hydrolysis to produce the corresponding seleninic acids. The selenoxides interact with nitrite more effectively than the corresponding seleninic acids to produce nitrate with the regeneration of the selenenyl amides. Therefore, the amount of nitrate formed in the reactions mainly depends on the stability of the selenoxides. Interestingly, substitution of an oxazoline moiety on the phenyl ring stabilizes the selenoxide, and therefore, enhances the isomerization of PN to nitrate.
Subject(s)
Azoles/chemistry , Carboxylic Acids/chemical synthesis , Organoselenium Compounds/chemistry , Organoselenium Compounds/chemical synthesis , Peroxynitrous Acid/chemistry , Azoles/chemical synthesis , Carboxylic Acids/chemistry , Catalysis , Crystallography, X-Ray , Hydrolysis , Isoindoles , Models, Molecular , Molecular Structure , StereoisomerismABSTRACT
Co-Co(2)B and Ni-Ni(3)B nanocomposites were synthesized by the reduction of Co(2+) and Ni(2+) ions using ammonia-borane in methanol. The Co-Ni-B nanocomposite was synthesized by the co-reduction of Co(2+) and Ni(2+) ions. The catalytic activities of these metal nanocomposites were studied for the dehydrogenation of ammonia-borane in methanol. Three moles of H(2) were liberated in 2.5 min and 4.2 min in case of Co-Co(2)B and Ni-Ni(3)B nanocomposites, respectively (catalyst/AB = 0.2). The Co-Ni-B nanocomposite showed greater activity compared to individual metal-metal boride nanocomposites: 3 moles of H(2) were liberated in 1.5 min (catalyst/AB = 0.2). The catalysts were highly recyclable and the activities remained almost unchanged even after several cycles.