Interactions of Fullerene‐Polyglycerol Sulfates at Viral and Cellular Interfaces

Understanding the mechanism of interactions of nanomaterials at biointerfaces is a crucial issue to develop new antimicrobial vectors. In this work, a series of water‐soluble fullerene‐polyglycerol sulfates (FPS) with different fullerene/polymer weight ratios and varying numbers of polyglycerol sulfate branches are synthesized, characterized, and their interactions with two distinct surfaces displaying proteins involved in target cell recognition are investigated. The combination of polyanionic branches with a solvent exposed variable hydrophobic core in FPS proves to be superior to analogs possessing only one of these features in preventing interaction of vesicular stomatitis virus coat glycoprotein (VSV‐G) with baby hamster kidney cells serving as a model of host cell. Interference with L‐selectin‐ligand binding is dominated by the negative charge, which is studied by two assays: a competitive surface plasmon resonance (SPR)‐based inhibition assay and the leukocyte cell (NALM‐6) rolling on ligands under flow conditions. Due to possible intrinsic hydrophobic and electrostatic effects of synthesized compounds, pico‐ to nanomolar half maximal inhibitory concentrations (IC₅₀) are achieved. With their highly antiviral and anti‐inflammatory properties, together with good biocompatibility, FPS are promising candidates for the future development towards biomedical applications.     

Complexation of free-base and 3d transition metal(II) phthalocyanines with fullerene C60: A dispersion-corrected DFT study

We performed a systematic comparative theoretical study of noncovalent interactions of free-base H₂Pc and a series of 3d transition metal(II) phthalocyanines (where the transition metals included manganese, iron, cobalt, nickel, copper and zinc) with fullerene C₆₀, by employing a DFT technique accounting for vdW interactions (PBE GGA functional with a dispersion correction by Grimme). We observed four different types of Pc interaction with fullerene cage, depending on central metal atom. Upon complexation with C₆₀, the macrocyclic plane undergoes distortion in all cases, to a different degree. Some correlation was observed between the calculated formation energies for Pc–fullerene complexes and intermolecular separations in them, where stronger binding is generally associated with shorter M^…C_C60 and N^…C_C60 distances. Despite of considerable differences in the structure of Pc–fullerene complexes, the latter do not exhibit notable variations in the distribution of electrostatic potential, contrary to spin density plots for open-shell species. Similarly, HOMO and LUMO distribution can vary within some limits.     

Noncovalent interactions of amino acids with fullerene C60: A dispersion-corrected DFT study

By using the general gradient approximation functional PBE with Grimme's empirical dispersion correction in conjunction with the double numerical basis set DNP, we studied the noncovalent interaction of twenty proteinogenic l-amino acids (AAs) with fullerene C₆₀. The calculations were performed both under vacuum conditions and in aqueous medium. We analyzed the calculated geometries and binding energies for AA+C₆₀ complexes, the shape of HOMO and LUMO orbitals and the corresponding gap energies. Generally, we found a poor correlation between binding energies calculated for AA+C₆₀ complexes in aqueous medium and hydrophobicity scales proposed by other other authors. Despite of C₆₀ cage can be envisioned as a typical hydrophobic surface, the AA adsorption apparently takes place according to a mechanism different from classical hydrophobic interactions, or due to a combination of several types of interactions with a limited contribution of hydrophobic mechanism.     

An unexpected biomaterial against SARS-CoV-2: Bio-polyphosphate blocks binding of the viral spike to the cell receptor

No other virus after the outbreak of the influenza pandemic of 1918 affected the world’s population as hard as the coronavirus SARS-CoV-2. The identification of effective agents/materials to prevent or treat COVID-19 caused by SARS-CoV-2 is an urgent global need. This review aims to survey novel strategies based on inorganic polyphosphate (polyP), a biologically formed but also synthetically available polyanionic polymeric material, which has the potential of being a potent inhibitor of the SARS-CoV-2 virus-cell-docking machinery. This virus attaches to the host cell surface receptor ACE2 with its receptor binding domain (RBD), which is present at the tips of the viral envelope spike proteins. On the surface of the RBD an unusually conserved cationic groove is exposed, which is composed of basic amino acids (Arg, Lys, and His). This pattern of cationic amino acids, the cationic groove, matches spatially with the anionic polymeric material, with polyP, allowing an electrostatic interaction. In consequence, the interaction between the RBD and ACE2 is potently blocked. PolyP is a physiological inorganic polymer, synthesized by cells and especially enriched in the blood platelets, which releases metabolically useful energy through enzymatic degradation and coupled ADP/ATP formation. In addition, this material upregulates the steady-state-expression of the mucin genes in the epithelial cells. We propose that polyP, with its two antiviral properties (blocking the binding of the virus to the cells and reinforcing the defense barrier against infiltration of the virus) has the potential to be a novel protective/therapeutic anti-COVID-19 agent.     

Spontaneous assembly of viruses on multilayered polymer surfaces

The idea that randomly arranged supermolecular species incorporated in a network medium can ultimately create ordered structures at the surface may be counterintuitive. However, such order can be accommodated by regulating dynamic and equilibrium driving forces. Here, we present the ordering of M13 viruses, highly complex biomacromolecules, driven by competitive electrostatic binding, preferential macromolecular interactions and the rigid-rod nature of the virus systems during alternating electrostatic assembly. The steric constraints inherent to the competitive charge binding between M13 viruses and two oppositely charged weak polyelectrolytes leads to interdiffusion and the virtual 'floating' of viruses to the surface. The result is the spontaneous formation of a two-dimensional monolayer structure of viruses atop a cohesive polyelectrolyte multilayer. We demonstrate that this viral-assembled monolayer can be a biologically tunable scaffold to nucleate, grow and align nanoparticles or nanowires over multiple length scales. This system represents an interface that provides a general platform for the systematic incorporation and assembly of organic, biological and inorganic materials.     

Electrostatic‐Driven Exfoliation and Hybridization of 2D Nanomaterials

Here, direct and effective electrostatic‐driven exfoliation of tungsten trioxide (WO₃) powder into atomically thin WO₃ nanosheets is demonstrated for the first time. Experimental evidence together with theoretical simulations clearly reveal that the strong binding of bovine serum albumin (BSA) on the surface of WO₃ via the protonation of ? NH₂ groups in acidic conditions leads to the effective exfoliation of WO₃ nanosheets under sonication. The exfoliated WO₃ nanosheets have a greatly improved dispersity and stability due to surface‐protective function of BSA, and exhibit a better performance and unique advantages in applications such as visible‐light‐driven photocatalysis, high‐capacity adsorption, and fast electrochromics. Further, simultaneous exfoliation and hybridization of WO₃ and MoS₂ nanosheets are demonstrated to form hybrid WO₃/MoS₂ nanosheets through respective electrostatic and hydrophobic interaction processes. In addition, this electrostatic‐driven exfoliation strategy is applied to exfoliate ultrathin black‐phosphorus nanosheets from its bulk to exhibit a greatly improved stability due to the surface protection by BSA. Overall, the work presented not only presents a facile and effective route to fabricate 2D materials but also brings more opportunities to exploit unusual exotic and synergistic properties in resulting hybrid 2D materials for novel applications.     

MXene-Based Aptameric Fluorosensor for Sensitive and Rapid Detection of COVID-19 (Small 23/2023)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-caused COVID-19 pandemic has rapidly escalated into the largest global health emergency, which pushes to develop detection kits for the detection of COVID-19 with high sensitivity, specificity, and fast analysis. Here, aptamer-functionalized MXene nanosheet is demonstrated as a novel bionanosensor that detects COVID-19. Upon binding to the spike receptor binding domain of SARS-CoV-2, the aptamer probe is released from MXene surface restoring the quenched fluorescence. The performances of the fluorosensor are evaluated using antigen protein, cultured virus, and swab specimens from COVID-19 patients. It is evidenced that this sensor can detect SARS-CoV-2 spike protein at final concentration of 38.9 fg mL⁻¹ and SARS-CoV-2 pseudovirus (limit of detection: 7.2 copies) within 30 min. Its application for clinical samples analysis is also demonstrated successfully. This work offers an effective sensing platform for sensitive and rapid detection of COVID-19 with high specificity.     

Polyelectrolyte multilayers for bio‐applications: recent advancements

The synergistic relationship between structure and the bulk properties of polyelectrolyte multilayer (PEM) films has generated tremendous interest in their application for loading and release of bioactive species. Layer‐by‐layer assembly is the simplest, cost effective process for fabrication of such PEMs films, leading to one of the most widely accepted platforms for incorporating biological molecules with nanometre precision. The bulk reservoir properties of PEM films render them a potential candidate for applications such as biosensing, drug delivery and tissue engineering. Various biomolecules such as proteins, DNA, RNA or other desired molecules can be incorporated into the PEM stack via electrostatic interactions and various other secondary interactions such as hydrophobic interactions. The location and availability of the biological molecules within the PEM stack mediates its applicability in various fields of biomedical engineering such as programmed drug delivery. The development of advanced technologies for biomedical applications using PEM films has seen rapid progress recently. This review briefly summarises the recent successes of PEM being utilised for diverse bio‐applications.Inspec keywords: polymer electrolytes, multilayers, polymer films, molecular biophysics, biomedical materials, biochemistryOther keywords: bioapplications, polyelectrolyte multilayer films, bioactive species, layer‐by‐layer assembly, biological molecules, biosensing, drug delivery, tissue engineering, biomolecules, proteins, DNA, RNA, electrostatic interactions, secondary interactions, hydrophobic interactions, biomedical engineering, programmed drug delivery, biomedical applications, PEM films     

SARS-CoV-2 RBD Neutralizing Antibody Induction is Enhanced by Particulate Vaccination

The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein is a candidate vaccine antigen that binds angiotensin-converting enzyme 2 (ACE2), leading to virus entry. Here, it is shown that rapid conversion of recombinant RBD into particulate form via admixing with liposomes containing cobalt-porphyrin-phospholipid (CoPoP) potently enhances the functional antibody response. Antigen binding via His-tag insertion into the CoPoP bilayer results in a serum-stable and conformationally intact display of the RBD on the liposome surface. Compared to other vaccine formulations, immunization using CoPoP liposomes admixed with recombinant RBD induces multiple orders of magnitude higher levels of antibody titers in mice that neutralize pseudovirus cell entry, block RBD interaction with ACE2, and inhibit live virus replication. Enhanced immunogenicity can be accounted for by greater RBD uptake into antigen-presenting cells in particulate form and improved immune cell infiltration in draining lymph nodes. QS-21 inclusion in the liposomes results in an enhanced antigen-specific polyfunctional T cell response. In mice, high dose immunization results in minimal local reactogenicity, is well-tolerated, and does not elevate serum cobalt levels. Taken together, these results confirm that particulate presentation strategies for the RBD immunogen should be considered for inducing strongly neutralizing antibody responses against SARS-CoV-2.     

Phosphorylation-induced conformational change responsible for the function of a myosin phosphatase inhibitor,CPI-17

The structures of CPI-17 (Protein kinase-C dependent protein phosphatase-1 (PP1) inhibitor of 17 kDa) in an inactive and an active form have been determined by multidimensional NMR spectroscopy. Comparison of the two structures revealed how the molecular switch turns on at atomic resolution. Using the NMR structure of CPI-17 in the active form, the binding with catalytic domain of PP1 (PP1c) was simulated and the binding model is proposed in this report. When the phospho-Thr38 docks to the catalytic site of PP1, possible interactions for the tight binding are found; one is electrostatic interaction between a negatively charged cluster on phospho-CPI-17 and an acidic groove of PP1c, and the other is hydrophobic interaction between a hydrophobic surface area of phospho-CPI-17 and a hydrophobic groove of PP1c.     

Cooperative Vaccinia Infection Demonstrated at the Single-Cell Level Using FluidFM

The mechanisms used by viruses to enter and replicate within host cells are subjects of intense investigation. These studies are ultimately aimed at development of new drugs that interfere with these processes. Virus entry and infection are generally monitored by dispensing bulk virus suspensions on layers of cells without accounting for the fate of each virion. Here, we take advantage of the recently developed FluidFM to deposit single vaccinia virions onto individual cells in a controlled manner. While the majority of virions were blocked prior to early gene expression, infection of individual cells increased in a nondeterministic fashion with respect to the number of viruses placed. Microscopic analyses of several stages of the virus lifecycle indicated that this was the result of cooperativity between virions during early stages of infection. These findings highlight the importance of performing controlled virus infection experiments at the single cell level.     

Hydrochar as protein support: preservation of biomolecule properties with non-covalent immobilization

In this work, the ConBr lectin was non-covalently immobilized onto hydrochar (HC). This carbonaceous material was produced by the hydrothermal carbonization of glucose and then put to interact with the lectin, aiming to immobilize the biomolecule via electrostatic interactions. Samples obtained after the interaction were characterized by CHNS elemental analysis, scanning electron microscopy and Fourier transform infrared spectroscopy (FTIR). FTIR results from the conjugated sample identified the presence of NH₂ ⁺ and NH₃ ⁺ groups of the protein and COO^? groups of the HC, indicating the occurrence of electrostatic interaction between the biomolecule and the support. Furthermore, the immobilization experiment was also performed using ConBr lectin marked with fluorescein isothiocyanate to assess the immobilization on the hydrochar using fluorescence emission analysis. Hemagglutination tests revealed that even after the conjugation with the HC, the agglutinating property of lectin toward erythrocytes (red blood cells) was preserved. Finally, our results indicate that non-covalent interactions represent an efficient mechanism for protein immobilization on the HC while maintaining the protein structure and its biological activity.     

Customizing Metal-Organic Frameworks by Lego-Brick Strategy for One-Step Purification of Ethylene from a Quaternary Gas Mixture

One-step purification of ethylene (C₂H₄) from a quaternary gas mixture of C₂H₆/C₂H₄/C₂H₂/CO₂ by adsorption is a promising separation process, yet developing adsorbents that synergistically capture various gas impurities remains challenging. Herein, a Lego-brick strategy is proposed to customize pore chemistry in a unified framework material. The ethane-selective MOF platform is further modified with customized binding sites to specifically adsorb acetylene and carbon dioxide, thus one-step purification of C₂H₄ with high productivity of polymer-grade product (134 mol kg⁻¹) is achieved on the assembly of porous coordination polymer-2,5-furandicarboxylic acid (PCP-FDCA) and PCP-5-aminoisophthalic acid (IPA-NH₂). Computational studies verify that the low-polarity surface of this MOFs-based platform provides a delicate environment for C₂H₆ recognition, and the specific binding sites (FDCA and IPA-NH₂) exhibit favorable trapping of C₂H₂ and CO₂ via C H^δ+···O^δ− and C^δ+···N^δ− electrostatic interactions, respectively. The proposed Lego-brick strategy to customize binding sites within the MOFs structure provides new ideas for the design of adsorbents for compounded separation tasks.     

Amplification-Free Detection of SARS-CoV-2 Down to Single Virus Level by Portable Carbon Nanotube Biosensors (Small 34/2023)

The rapid and sensitive detection of trace-level viruses in a simple and reliable way is of great importance for epidemic prevention and control. Here, a multi-functionalized floating gate carbon nanotube field effect transistor (FG-CNT FET) based biosensor is reported for the single virus level detection of SARS-CoV-2 virus antigen and RNA rapidly with a portable sensing platform. The aptamers functionalized sensors can detect SARS-CoV-2 antigens from unprocessed nasopharyngeal swab samples within 1 min. Meanwhile, enhanced by a multi-probe strategy, the FG-CNT FET-based biosensor can detect the long chain RNA directly without amplification down to single virus level within 1 min. The device, constructed with packaged sensor chips and a portable sensing terminal, can distinguish 10 COVID-19 patients from 10 healthy individuals in clinical tests both by the RNAs and antigens by a combination detection strategy with an combined overall percent agreement (OPA) close to 100%. The results provide a general and simple method to enhance the sensitivity of FET-based biochemical sensors for the detection of nucleic acid molecules and demonstrate that the CNT FG FET biosensor is a versatile and reliable integrated platform for ultrasensitive multibiomarker detection without amplification and has great potential for point-of-care (POC) clinical tests.     

Hydrophobin as a Nanolayer Primer That Enables the Fluorinated Coating of Poorly Reactive Polymer Surfaces

A new and simple method is presented to fluorinate the surfaces of poorly reactive hydrophobic polymers in a more environmentally friendly way using the protein hydrophobin (HFBII) as a nanosized primer layer. In particular, HFBII, via electrostatic interactions, enables the otherwise inefficient binding of a phosphate‐terminated perfluoropolyether onto polystyrene, polypropylene, and low‐density polyethylene surfaces. The binding between HFBII and the perfluoropolyether depends significantly on the environmental pH, reaching the maximum stability at pH 4. Upon treatment, the polymeric surfaces mostly retain their hydrophobic character but also acquire remarkable oil repellency, which is not observed in the absence of the protein primer. The functionalization proceeds rapidly and spontaneously at room temperature in aqueous solutions without requiring energy‐intensive procedures, such as plasma or irradiation treatments.     

Triplet molecules of the D5 symmetry group based on C60 fullerene

The possibility of observing a non-zero-spin triplet state in highly symmetric derivatives of fullerene molecules with five double bonds, representing isomers of the type D₅-C₆₀(R-r ₆-R)₅ (where R = H or CH₃), is assessed based on the results of quantum-chemical calculations. The energies of isomer formation (endo-and exothermal process for the hydrogenated and methylated isomers, respectively) and the energies of terms are determined. The ground state corresponding to a non-zero-spin triplet e ₁ ² (³A₂) occurs approximately 0.3 eV below the zero-spin states. The results can be interpreted within the framework of the tight binding approximation for the pπ basis set orbitals of fullerene molecules (representing radially directed C2p hybrid atomic orbitals). The character of the open electron shell of isomers, delocalized over a large fullerene surface, suggests that, with high probability, the above non-zero-spin triplet state (rather than the e ₁ ² (¹E₂) state stabilized by the Jahn-Teller effect) is the ground state of the system.     

Multi-walled carbon nanotubes coated with rare earth fluoride EuF3 and TbF3 nanoparticles

EuF₃ and TbF₃ were successfully coated on the multi-walled carbon nanotubes (MWNTs) via the intermediate of noncovalent hydrophobic interactions of the MWNTs surface with sodium dodecyl sulfate (SDS). They were characterized by X-ray powder diffraction (XRD), transmission electron microscopy (TEM) and high-resolution transmission electron microscopy (HRTEM). The nanoparticle sizes of rare earth fluorides on MWNTs are less than 10 nm. The photophysical properties of the composites were investigated, which indicated the rare earth fluorides/MWNTs composites exhibited the optical transitions within the 4f shell of the rare earth ions.     

Guided Molecular Assembly on a Locally Reactive 2D Material

Atomically precise engineering of the position of molecular adsorbates on surfaces of 2D materials is key to their development in applications ranging from catalysis to single‐molecule spintronics. Here, stable room‐temperature templating of individual molecules with localized electronic states on the surface of a locally reactive 2D material, silicene grown on ZrB₂, is demonstrated. Using a combination of scanning tunneling microscopy and density functional theory, it is shown that the binding of iron phthalocyanine (FePc) molecules is mediated via the strong chemisorption of the central Fe atom to the sp³‐like dangling bond of Si atoms in the linear silicene domain boundaries. Since the planar Pc ligand couples to the Fe atom mostly through the in‐plane d orbitals, localized electronic states resembling those of the free molecule can be resolved. Furthermore, rotation of the molecule is restrained because of charge rearrangement induced by the bonding. These results highlight how nanoscale changes can induce reactivity in 2D materials, which can provide unique surface interactions for enabling novel forms of guided molecular assembly.     

Cover Picture: A Two‐Dimensional Porphyrin‐Based Porous Network Featuring Communicating Cavities for the Templated Complexation of Fullerenes (Adv. Mater. 3/2006)

A 2D porous network has been realized by self‐assembly of porphyrin modules on a silver surface, as reported by Diederich and co‐workers on p. 275. The so‐formed pores are able to host single fullerene molecules and mediate long‐range interactions between such carbon guests, resulting in the formation of large supramolecular chains and islands. The cover shows a scanning tunnelling microscopy image of several single C₆₀ molecules (large green protrusions) hosted in the 2D porous network. As indicated by the molecular model, each pore is formed by the symmetric arrangement of three porphyrin molecules and the fullerene guest is located exactly in the center of the cavity.     

A Vicenary Analysis of SARS-CoV-2 Genomes

Coronaviruses are responsible for various diseases ranging from the common cold to severe infections like the Middle East syndromes and the severe acute respiratory syndrome. However, a new coronavirus strain known as COVID-19 developed into a pandemic resulting in an ongoing global public health crisis. Therefore, there is a need to understand the genomic transformations that occur within this family of viruses in order to limit disease spread and develop new therapeutic targets. The nucleotide sequences of SARS-CoV-2 are consist of several bases. These bases can be classified into purines and pyrimidines according to their chemical composition. Purines include adenine (A) and guanine (G), while pyrimidines include cytosine (C) and tyrosine (T). There is a need to understand the spatial distribution of these bases on the nucleotide sequence to facilitate the development of antivirals (including neutralizing antibodies) and epitomes necessary for vaccine development. This study aimed to evaluate all the purine and pyrimidine associations within the SARS-CoV-2 genome sequence by measuring mathematical parameters including; Shannon entropy, Hurst exponent, and the nucleotide guanine-cytosine content. The Shannon entropy is used to identify closely associated sequences. Whereas Hurst exponent is used to identifying the auto-correlation of purine-pyrimidine bases even if their organization differs. Different frequency patterns can be used to determine the distribution of all four proteins and the density of each base. The GC-content is used to understand the stability of the DNA. The relevant genome sequences were extracted from the National Center for Biotechnology Information (NCBI) virus database. Furthermore, the phylogenetic properties of the COVID-19 virus were characterized to compare the closeness of the COVID-19 virus with other coronaviruses by evaluating the purine and pyrimidine distribution.