Formation of Amphiphilic Zwitterionic Thin Poly(SBMA-co-TFEMA) Brushes on Solid Surfaces for Marine Antifouling Applications.

Water molecules can bind to zwitterionic polymers, such as carboxybetaine and sulfobetaine, forming strong hydration layers along the polymer chains. Such hydration layers act as a barrier to impede the attachment of marine fouling organisms; therefore, zwitterionic polymer coatings have been of considerable interest as marine antifouling coatings. However, recent studies have shown that severe adsorption of marine sediments occurs on zwitterionic-polymer-coated surfaces, resulting in the degradation of their marine antifouling performance. Therefore, a novel approach for forming amphiphilic zwitterionic polymers using zwitterionic and hydrophobic monomers is being investigated to simultaneously inhibit both sediment adsorption and marine fouling. In this study, amphiphilic zwitterionic thin polymer brushes composed of sulfobetaine methacrylate (SBMA) and trifluoroethyl methacrylate (TFEMA) were synthesized on Si/SiO2 surfaces via surface-initiated atom transfer radical polymerization. For this, a facile metal-ion-mediated method was developed for immobilizing polymerization initiators on solid substrates to subsequently form poly(SBMA-co-TFEMA) brushes on the initiator-coated substrate surface. Poly(SBMA-co-TFEMA) brushes with various SBMA/TFEMA ratios were prepared to determine the composition at which both marine diatom adhesion and sediment adsorption can be prevented effectively. The results indicate that poly(SBMA-co-TFEMA) brushes prepared with an SBMA/TFEMA ratio of 3:7 effectively inhibit both sediment adsorption and marine diatom adhesion, thereby exhibiting balanced marine antifouling properties. Thus, the findings of this study provide important insights into the design of amphiphilic marine antifouling materials.

Role of PemI in the Staphylococcus aureus PemIK toxin-antitoxin complex: PemI controls PemK by acting as a PemK loop mimic.

Staphylococcus aureus is a notorious and globally distributed pathogenic bacterium. New strategies to develop novel antibiotics based on intrinsic bacterial toxin-antitoxin (TA) systems have been recently reported. Because TA systems are present only in bacteria and not in humans, these distinctive systems are attractive targets for developing antibiotics with new modes of action. S. aureus PemIK is a type II TA system, comprising the toxin protein PemK and the labile antitoxin protein PemI. Here, we determined the crystal structures of both PemK and the PemIK complex, in which PemK is neutralized by PemI. Our biochemical approaches, including fluorescence quenching and polarization assays, identified Glu20, Arg25, Thr48, Thr49, and Arg84 of PemK as being important for RNase function. Our study indicates that the active site and RNA-binding residues of PemK are covered by PemI, leading to unique conformational changes in PemK accompanied by repositioning of the loop between ß1 and ß2. These changes can interfere with RNA binding by PemK. Overall, PemK adopts particular open and closed forms for precise neutralization by PemI. This structural and functional information on PemIK will contribute to the discovery and development of novel antibiotics in the form of peptides or small molecules inhibiting direct binding between PemI and PemK.

Structural Insights into the Penicillin-Binding Protein 4 (DacB) from Mycobacterium tuberculosis.

Mycobacterium tuberculosis, a major cause of mortality from a single infectious agent, possesses a remarkable mycobacterial cell envelope. Penicillin-Binding Proteins (PBPs) are a family of bacterial enzymes involved in the biosynthesis of peptidoglycan. PBP4 (DacB) from M. tuberculosis (MtbPBP4) has been known to function as a carboxypeptidase, and the role and significance of carboxypeptidases as targets for anti-tuberculosis drugs or antibiotics have been extensively investigated over the past decade. However, their precise involvement remains incompletely understood. In this study, we employed predictive modeling and analyzed the three-dimensional structure of MtbPBP4. Interestingly, MtbPBP4 displayed a distinct domain structure compared to its homologs. Docking studies with meropenem verified the presence of active site residues conserved in PBPs. These findings establish a structural foundation for comprehending the molecular function of MtbPBP4 and offer a platform for the exploration of novel antibiotics.

Nanomaterials multifunctional behavior for enlightened cancer therapeutics.

Cancer is an outrageous disease with uncontrolled differentiation, growth, and migration to the other parts of the body. It is the second-most common cause of death both in the U.S. and worldwide. Current conventional therapies, though much improved and with better prognosis, have several limitations. Chemotherapeutic agents, for instance, are cytotoxic to both tumor and healthy cells, and the non-specific distribution of drugs at tumor sites limits the dose administered. Nanotechnology, which evolved from the coalescence and union of varied scientific disciplines, is a novel science that has been the focus of much research. This technology is generating more effective cancer therapies to overcome biomedical and biophysical barriers against standard interventions in the body; its unique magnetic, electrical, and structural properties make it a promising tool. This article reviews endogenous- and exogenous-based stimulus-responsive drug delivery systems designed to overcome the limitations of conventional therapies. The article also summarizes the study of nanomaterials, including polymeric, gold, silver, magnetic, and quantum dot nanoparticles. Though an array of drug delivery systems has so far been proposed, there remain many challenges and concerns that should be addressed in order to fill the gaps in the field. Prominence is given to drug delivery systems that employ external- and internal-based stimuli and that are emerging as promising tools for cancer therapeutics in clinical settings.

Engineered nanoparticles for imaging and drug delivery in colorectal cancer.

Colorectal cancer (CRC) is one of the deadliest diseases worldwide due to a lack of early detection methods and appropriate drug delivery strategies. Conventional imaging techniques cannot accurately distinguish benign from malignant tissue, leading to frequent misdiagnosis or diagnosis at late stages of the disease. Novel screening tools with improved accuracy and diagnostic precision are thus required to reduce the mortality burden of this malignancy. Additionally, current therapeutic strategies, including radio- and chemotherapies carry adverse side effects and are limited by the development of drug resistance. Recent advances in nanotechnology have rendered it an attractive approach for designing novel clinical solutions for CRC. Nanoparticle-based formulations could assist early tumor detection and help to overcome the limitations of conventional therapies including poor aqueous solubility, nonspecific biodistribution and limited bioavailability. In this review, we shed light on various types of nanoparticles used for diagnosis and drug delivery in CRC. In addition, we will explore how these nanoparticles can improve diagnostic accuracy and promote selective drug targeting to tumor sites with increased efficiency and reduced cytotoxicity against healthy colon tissue.

Surface Coating with Naphthalene Trisulfonate/Hafnium(IV) Complexes: Versatility and Post-Functionalization.

Naphthalene trisulfonate is found to have versatile surface coating capability when combined with hafnium(IV) ions, thereby forming complexes. Solid substrates such as titanium/titanium dioxide, glass, and nylon immersed in a solution of naphthalene trisulfonate and HfIV produces naphthalene trisulfonate/HfIV complex coating. The coating is not produced when the HfIV ions are absent or when naphthalene monosulfonate replaces naphthalene trisulfonate; this indicates the significance of HfIV ions and multiple sulfonates in this coating system. The versatile surface coating property of naphthalene trisulfonate/HfIV complexes is attributed to the coexistence of hydrophobic aromatic and hydrophilic side groups in naphthalene trisulfonate. Additionally, HfIV ion-mediated cross-linking reactions between naphthalene trisulfonate molecules induce molecular assembly, facilitating versatile surface coating. Post-functionalization of the coating is accomplished through additional HfIV-mediated coordinate bond formation; alginate and λ-carrageenan are successfully grafted onto the coating for nonbiofouling applications.

Effect of N-Methylation on Dopamine Surface Chemistry.

Dopamine (DA) surface chemistry has received significant attention because of its applicability in a wide range of research fields and the ability to graft functional molecules onto numerous solid surfaces. Various DA derivatives have been newly synthesized to identify key factors affecting the coating efficiency and to advance the coating system development. The oxidation of catechol into quinone followed by internal cyclization via the nucleophilic attack of primary amine is crucial for DA-based surface coating. Thus, it is expected that the amine group's nucleophilicity control directly affects the coating efficiency. However, it has not been systematically investigated, and most studies have been conducted with the focus on the transformation of amines into amides, despite such approaches decreasing the coating efficiency; the nitrogen in amides is less nucleophilic than that in free amines. In this study, we investigated the effect of N-alkylation on dopamine surface chemistry. N,N-Dimethyldopamine (DMDA) was newly synthesized, and the coating efficiency was systematically compared with DA and N-methyldopamine (MDA). DA N-monomethylation improved the coating rate by increasing the nitrogen nucleophilicity, whereas N,N-dimethylation dramatically decreased the DA surface coating property. In addition, MDA remained capable of universal surface coating and secondary reactions using the surface catechols. This study provides opportunities for developing coating materials with advanced functions and an improved coating rate.

Coordination-Driven Surface Zwitteration for Antibacterial and Antifog Applications.

The enhancement of surface wettability by hydrophilic polymer coatings has been of great interest because it has been used to address several technical challenges such as biofouling and surface fogging. Among the hydrophilic polymers, zwitterionic polymers have been extensively utilized to coat solid surfaces due to their excellent capability to bind water molecules, thereby forming dense hydration layers on the solid surfaces. For these zwitterionic polymers to function appropriately on the solid surfaces, techniques for fixing polymers onto the solid surface with high efficiency are required. Herein, we report a new approach to graft zwitterionic polymers onto solid substrates. The approach is based on the mussel-inspired surface chemistry and metal coordination. It consists of polydopamine coating and the coordination-driven grafting of the zwitterionic polymers. Polydopamine coating enables the versatile surface immobilization of catechols. Zwitterionic polymers are then easily fixed onto the catechol-immobilized surface by metal-mediated crosslinking reactions. Using this approach, nanometer-thick zwitterionic polymer layers that are highly resistant to bacterial adhesion and fog generation could be successfully fabricated on solid substrates in a substrate-independent manner.

The Fabrication of Cesium Lead Bromide-Coated Cellulose Nanocomposites and Their Effect on the Detection of Nitrogen Gas.

In this work, we fabricate cesium lead bromide nanofibers (CsPbBr3 NFs) via the attachment of cesium lead bromide nanocrystals (CsPbBr3 NCs) on the surface of electrospun cellulose nanofibers (CNFs) and employ them in a sensor to effectively detect gaseous nitrogen. The CsPbBr3 NFs are produced initially by producing CsPbBr3 NCs through hot injection and dispersing on hexane, followed by dipping CNFs and ultrasonicate for 1 h. Morphological characterization through visual, SEM and TEM image, and crystalline structure analysis by XRD and FT-IR analysis of CsPbBr3 NFs and NCs show similar spectra except for PL due to unavoidable damage during the ultrasonication. Gaseous nitrogen is subsequently detected using the photoluminescence (PL) property of CsPbBr3 NFs, in which the PL intensity dramatically decreases under various flow rate. Therefore, we believe that the proposed CsPbBr3 NFs show significant promise for use in detection sensors in various industrial field and decrease the potential of fatal damage to workers due to suffocation.

Universal Surface Coating with a Non-Phenolic Molecule, Sulfonated Pyrene.

Nature-inspired small molecules such as catecholamines and polyphenols have gained a great deal of attention because of the exceptional surface-coating property that is applicable to many diverse substrates. Many researchers have conducted studies to expand molecular pools with surface-coating properties, but previous reports have still been limited to phenolic molecules as surface-coating agents. In this study, we describe for the first time the material-independent coating properties of nonphenolic molecules, namely, sulfonated pyrenes with ZrIV ions. Owing to the binding capability with several oxygen-containing ligands, ZrIV can be used for the molecular assembly of sulfonated pyrenes. We also report on the mixing of multiple sulfonated pyrenes and ZrIV results in cross-linked complexes that can coat diverse solid substrates. The resulting coating can serve as a platform for grafting functional polysaccharides.

Au@Zr-based metal-organic framework composite as an immunosensing platform for determination of hepatitis B virus surface antigen.

An ultrasensitive electrochemical immunosensor has been prepared using an immunofunctionalized zirconium (Zr)-based metal-organic framework (MOF) with gold (Au) decoration Au@UiO-66(NH2) composite-coated glassy carbon electrode (GCE) for the determination of infectious hepatitis B surface antigen (HBsAg). We fabricated GCE with specific composite via immune-functionalization using anti-HBsAg with Au nanoparticles embedded in UiO-66(NH2). The electrochemical sensing performance of the immunofunctionalized Au@UiO-66(NH2)/GCE with HBsAg was characterized by cyclic voltammetry and differential pulse voltammetry. Under optimized conditions, there was a linear dynamic relationship in the buffer system between the electrical signal and HBsAg levels over the range 1.13 fg mL-1-100 ng mL-1 (R2 = 0.999) with a detection limit of 1.13 fg mL-1. The total analysis time was 15 min per sample. Further validations were performed with HBsAg-spiked human serum samples, and similar detection limits as in the buffer system were observed with reduced signal intensities at lower concentrations of HBsAg (1, 10, and 100 fg mL-1) and minimal interference. The HBsAg electrochemical immunosensing assay had good selectivity and excellent reproducibility, thereby indicating its significant potential in the super-fast diagnosis of hepatitis B.

Zr(IV) Coordination Chemistry for Cell-Repellent Alginate Coatings: The Effect of Surface Functional Groups.

Surface modification using alginic acid and its salt, alginate (Alg), has attracted much attention owing to its potential applications in various fields, including tissue engineering, drug delivery, antiplatelet surface preparation, and energy-storage technologies. In these applications, efficient immobilization of Alg on the solid surface is required because the delamination of the surface-bound Alg eventually leads to a significant decrease in its function. Therefore, much effort has been made to introduce Alg onto solid surfaces in a stable manner. Despite recent advances, existing methods for immobilizing Alg on surfaces have some limitations: (i) derivatization of Alg is typically also required and (ii) these methods only function under specific reaction conditions. Herein, we report a Zr(IV)-mediated strategy to immobilize Alg on solid surfaces. We demonstrate efficient Alg grafting onto carboxyl-, catechol-, polydopamine-, and tannic acid-functionalized surfaces via Zr(IV)-mediated cross-linking reactions. This strategy yields Alg multilayers that suppress fibroblast and platelet adhesion onto the solid surfaces. Furthermore, we show that the Alg multilayers can be selectively constructed on specific sites of solid surfaces. Given its ease of use and the wide selection of available carboxyl polymers, the current strategy is expected to be a useful tool for preparing functional polymer films for various applications.

Mussel-Inspired, One-Step Thiol Functionalization of Solid Surfaces.

Mussel-inspired surface chemistry, in which catechol derivatives play an important role, has garnered extensive research interest owing to material-independent surface coating capability and easy implementation to a wide range of applications. Generally, sequential reactions comprising catechol oxidation, intramolecular reaction of oxidized catechols with nucleophiles, and intermolecular assembly result in polymers that can adhere to many diverse surfaces. Although amines and thiols have similar reactivity toward oxidized catechols, most studies have been conducted with catechol and amine groups as essentials. Surface coating with catechol-thiol has not been investigated. In this study, we show that 4-(2-mercapto-ethyl)-benzene-1,2-diol (catechol-thiol) can serve as a surface coating agent in the presence of a strong oxidant. A wide range of materials are coated with catechol-thiol, and an additional grafting of the functional molecules onto the surface is also performed through well-established thiol chemistry, Michael addition, and thiol-ene reaction.

Red Algae-Derived Carrageenan Coatings for Marine Antifouling Applications.

We report a facile approach for the fabrication of a marine antifouling coating using the red algae-derived polysaccharide, carrageenan (CAR). Because CAR is hydrophilic and negatively charged, we hypothesized that it would form strong hydration layers upon adsorption onto solid surfaces, thereby exhibiting marine antifouling properties. Although various types of CAR can be used for marine antifouling, a universally applicable coating method has not yet been developed; thus, a systematic study on the marine antifouling property of CAR coating is lacking. Here, we fabricated a versatile CAR coating via ZrIV-mediated multiple cross-linking reactions between the sulfate groups of CAR and metal ions and successfully deposited κ-, ι-, and λ-CAR onto solid surfaces. Specifically, λ-CAR showed superior marine antifouling performance, as evidenced by the results of the marine diatom adhesion assays.

Functional insights into the Streptococcus pneumoniae HicBA toxin-antitoxin system based on a structural study.

Streptococcus pneumonia has attracted increasing attention due to its resistance to existing antibiotics. TA systems are essential for bacterial persistence under stressful conditions such as nutrient deprivation, antibiotic treatment, and immune system attacks. In particular, S. pneumoniae expresses the HicBA TA gene, which encodes the stable HicA toxin and the labile HicB antitoxin. These proteins interact to form a non-toxic TA complex under normal conditions, but the toxin is activated by release from the antitoxin in response to unfavorable growth conditions. Here, we present the first crystal structure showing the complete conformation of the HicBA complex from S. pneumonia. The structure reveals that the HicA toxin contains a double-stranded RNA-binding domain that is essential for RNA recognition and that the C-terminus of the HicB antitoxin folds into a ribbon-helix-helix DNA-binding motif. The active site of HicA is sterically blocked by the N-terminal region of HicB. RNase activity assays show that His36 is essential for the ribonuclease activity of HicA, and nuclear magnetic resonance (NMR) spectra show that several residues of HicB participate in binding to the promoter DNA of the HicBA operon. A toxin-mimicking peptide that inhibits TA complex formation and thereby increases toxin activity was designed, providing a novel approach to the development of new antibiotics.

4-(3-Aminopropyl)-benzene-1,2-diol: An Improved Material-Independent Surface-Coating Reagent Compared to Dopamine.

Dopamine surface chemistry has been of great interest because of its universal coating property and ability to transform nonadhesive molecules into adhesive molecules. Catechol oxidation and intramolecular cyclization underlie the unique property of dopamine (DA) surface chemistry and provide clues for developing new surface modification reagents such as norepinephrine, 5-pyrogallol-2-aminoethane, and perfluorinated DA derivatives. Based on these inspiring properties, a fast and universal surface chemistry technique using 4-(3-aminopropyl)-benzene-1,2-diol (3-catecholpropanamine, CPA) is reported herein. A single carbon insertion in the aliphatic chain of DA gives rise to the significantly accelerated intermolecular assembly and surface coating of CPA. The effect of CPA conjugation on an anticoagulant polysaccharide coating is also investigated. The use of CPA instead of DA to make polysaccharide coating materials improves the coating rate, while maintaining excellent antiplatelet performance on the coated surface.

Oxidation-Mediated, Zwitterionic Polydopamine Coatings for Marine Antifouling Applications.

We synthesized a zwitterionic dopamine derivative ( ZW-DOPA) containing both catechol and amine groups, and we demonstrated an excellent marine antifouling surface by controlling the oxidation of ZW-DOPA. The oxidation was mediated by the deprotonation of catechol or the addition of an oxidant (ammonium persulfate (AP) or sodium periodate (NaIO4)). The oxidation and subsequent molecular transformation of ZW-DOPA was investigated over time by UV-vis spectroscopy. Among the different oxidation conditions tested, NaIO4-induced ZW-DOPA coating was the most efficient and successfully formed on various substrates, such as titanium dioxide, stainless steel, and nylon. Compared with uncoated substrates, ZW-DOPA-coated substrates showed high resistance to marine diatom adhesion. Considering the ease of use and substrate independence of the ZW-DOPA coating, this method shows promise as a basis for inhibiting marine fouling on a variety of substrates used in the marine industry and aquatic environments.

Antibacterial Film Formation through Iron(III) Complexation and Oxidation-Induced Cross-Linking of OEG-DOPA.

Catechols are prone to oxidative polymerization as well as complex formation with metal ions. These two features of catechols have played an important role in the construction of functional films on various surfaces. For example, marine antifouling films and antibacterial films were successfully prepared by oxidative polymerization and metal complexation of catechol-containing molecules, respectively. However, the effect of simultaneous metal complexation and oxidative polymerization on functional film formation has not yet been fully investigated. Herein, as a derivative of 3-(3,4-dihydroxyphenyl)-l-alanine (DOPA), we synthesized an ethylene glycol-derivatized DOPA (OEG-DOPA) and formed OEG-DOPA thin films based on (1) oxidative polymerization and (2) the complexation between catechol groups of OEG-DOPA and iron(III) (FeIII) ions. Either or both approaches were used for the film formation. OEG-DOPA film formation was characterized by ellipsometry, contact angle goniometry, field emission scanning electron microscopy, and X-ray photoelectron spectroscopy. Among the conditions used, the formation of a uniform film was only achieved with the dual cross-linking system of FeIII complexation and oxidation-induced covalent bond formation. Compared to the uncoated substrate and other OEG-DOPA films prepared under different conditions, the uniform OEG-DOPA film strongly inhibited bacterial adhesion, showing excellent antibacterial capability. We think that our surface-coating strategy can be applied to medical devices, tools, and implants where bacterial adhesion and biofilm formation should be prevented. This work can also serve as a basis for the construction of functional thin films for other catechol-functionalized materials.

Functional details of the Mycobacterium tuberculosis VapBC26 toxin-antitoxin system based on a structural study: insights into unique binding and antibiotic peptides.

Toxin-antitoxin (TA) systems are essential for bacterial persistence under stressful conditions. In particular, Mycobacterium tuberculosis express VapBC TA genes that encode the stable VapC toxin and the labile VapB antitoxin. Under normal conditions, these proteins interact to form a non-toxic TA complex, but the toxin is activated by release from the antitoxin in response to unfavorable conditions. Here, we present the crystal structure of the M. tuberculosis VapBC26 complex and show that the VapC26 toxin contains a pilus retraction protein (PilT) N-terminal (PIN) domain that is essential for ribonuclease activity and that, the VapB26 antitoxin folds into a ribbon-helix-helix DNA-binding motif at the N-terminus. The active site of VapC26 is sterically blocked by the flexible C-terminal region of VapB26. The C-terminal region of free VapB26 adopts an unfolded conformation but forms a helix upon binding to VapC26. The results of RNase activity assays show that Mg2+ and Mn2+ are essential for the ribonuclease activity of VapC26. As shown in the nuclear magnetic resonance spectra, several residues of VapB26 participate in the specific binding to the promoter region of the VapBC26 operon. In addition, toxin-mimicking peptides were designed that inhibit TA complex formation and thereby increase toxin activity, providing a novel approach to the development of new antibiotics.

Correction to: Recent advances in molybdenum disulfide-based electrode materials for electroanalytical applications.

The original version of this article unfortunately missed Prof. A.T. Ezhil Vilian's project number in Acknowledgements. The missing project number is 2017R1D1A1B03034977.