Dehydropeptide supramolecular hydrogels and nanostructures as potential peptidomimetic biomedical materials

Supramolecular peptide hydrogels are gaining increased attention, owing to their potential in a variety of biomedical applications. Their physical properties are similar to those of the extracellular matrix (ECM), which is key to their applications in the cell culture of specialized cells, tissue engineering, skin regeneration, and wound healing. The structure of these hydrogels usually consists of a di- or tripeptide capped on the N-terminus with a hydrophobic aromatic group, such as Fmoc or naphthalene. Although these peptide conjugates can offer advantages over other types of gelators such as cross-linked polymers, they usually possess the limitation of being particularly sensitive to proteolysis by endogenous proteases. One of the strategies reported that can overcome this barrier is to use a peptidomimetic strategy, in which natural amino acids are switched for non-proteinogenic analogues, such as D-amino acids, β-amino acids, or dehydroamino acids. Such peptides usually possess much greater resistance to enzymatic hydrolysis. Peptides containing dehydroamino acids, i.e., dehydropeptides, are particularly interesting, as the presence of the double bond also introduces a conformational restraint to the peptide backbone, resulting in (often predictable) changes to the secondary structure of the peptide. This review focuses on peptide hydrogels and related nanostructures, where α,β-didehydro-α-amino acids have been successfully incorporated into the structure of peptide hydrogelators, and the resulting properties are discussed in terms of their potential biomedical applications. Where appropriate, their properties are compared with those of the corresponding peptide hydrogelator composed of canonical amino acids. In a wider context, we consider the presence of dehydroamino acids in natural compounds and medicinally important compounds as well as their limitations, and we consider some of the synthetic strategies for obtaining dehydropeptides. Finally, we consider the future direction for this research area.This work was supported by the Portuguese Foundation for Science and Technology (FCT) in the framework of the Strategic Funding of CQUM (UID/QUI/00686/2019). FCT, FEDER, PORTUGAL2020 and COMPETE2020 are also acknowledged for funding under research project PTDC/QUI-QOR/29015/2017 (POCI-01-0145-FEDER-029015)

Excimer laser surface modification: Process and properties

Surface modification can improve materials for structural, tribological, and corrosion applications. Excimer laser light has been shown to provide a rapid means of modifying surfaces through heat treating, surface zone refining, and mixing. Laser pulses at modest power levels can easily melt the surfaces of many materials. Mixing within the molten layer or with the gas ambient may occur, if thermodynamically allowed, followed by rapid solidification. The high temperatures allow the system to overcome kinetic barriers found in some ion mixing experiments. Alternatively, surface zone refinement may result from repeated melting-solidification cycles. Ultraviolet laser light couples energy efficiently to the surface of metallic and ceramic materials. The nature of the modification that follows depends on the properties of the surface and substrate materials. Alloying from both gas and predeposited layer sources has been observed in metals, semiconductors, and ceramics as has surface enrichment of Cr by zone refinement of stainless steel. Rapid solidification after melting often results in the formation of nonequilibrium phases, including amorphous materials. Improved surface properties, including tribology and corrosion resistance, are observed in these materials

A Dilatometric Study of Graphite Electrodes during Cycling with X-ray Computed Tomography

Graphite is the most commonly used anode material in commercial lithium-ion batteries (LiBs). Understanding the mechanisms driving the dimensional changes of graphite can pave the way to methods for inhibiting degradation pathways and possibly predict electrochemical performance loss. In this study, correlative microscopy tools were used alongside electrochemical dilatometry (ECD) to provide new insights into the dimensional changes during galvanostatic cycling. X-ray computed tomography (CT) provided a morphological perspective of the cycled electrode so that the effects of dilation and contraction on effective diffusivity and electrode pore phase volume fraction could be examined. During the first cycle, the graphite electrode underwent thickness changes close to 9% after lithiation and, moreover, it did not return to its initial thickness after subsequent delithiation. The irreversible dilation increased over subsequent cycles. It is suggested the primary reason for this dilation is electrode delamination. This is supported by the finding that the electrode porosity remained mostly unchanged during cycling, as revealed by X-ray CT

Up in smoke: Considerations for lithium-ion batteries in disposable e-cigarettes

In recent years, the use of disposable electric (e)-cigarettes containing lithium-ion batteries in the UK has led to remarkable wastage, the full environmental impact of which is yet to be realized. This study investigates the suitability for reuse and safety aspects of cells found in disposable e-cigarettes. Through electrochemical and safety characterization techniques, the cells’ performance and hazards were evaluated. Rate capability and long-term cycling experiments showed that cells sold as disposable were capable of completing 474 cycles at 1C charge/discharge before reaching 80% capacity fade. A nail penetration test revealed significant gas expulsion and a maximum temperature of 495°C. However, the cell format prevented significant material ejection. This work outlines the potential health hazards and highlights the possibility for second-life use of disposable e-cigarette cells, shedding light on the environmental impact and safety considerations

An Advanced Microstructural and Electrochemical Datasheet on 18650 Li-Ion Batteries with Nickel-Rich NMC811 Cathodes and Graphite-Silicon Anodes

Cylindrical lithium-ion batteries are used across a wide range of applications from spacesuits to automotive vehicles. Specifically, many manufacturers are producing cells in the 18650 geometry i.e. a steel cylinder of diameter and length ca. 18 and 65 mm, respectively. One example is the LG Chem INR18650 MJ1 (nominal values: 3.5 Ah, 3.6 V, 12.2 Wh). This article describes the electrochemical performance and microstructural assembly of such cells, where all the under-pinning data is made openly available for the benefit of the wider community. The charge-discharge capacity is reported for 400 operational cycles via the manufacturer's guidelines along with full-cell, individual electrode coating and particle 3D imaging. Within the electrochemical data, the distinction between protocol transition, beginning-of-life (BoL) capacity loss, and prolonged degradation is outlined and, subsequently, each aspect of the microstructural characterization is broken down into key metrics that may aid in understanding such degradation (e.g. electrode assembly layers, coating thickness, areal loading, particle size and shape). All key information is summarized in a quick-access advanced datasheet in order to provide an initial baseline of information to guide research paths, inform experiments and aid computational modellers

Hydrogels and nanostructures formed from ciprofloxacin–peptide conjugates

Ciprofloxacin is a broad-spectrum fluoroquinolone antibiotic that possesses potent activity against both Gram-positive and Gram-negative bacteria and is used to treat many infections. Despite its widespread use, ciprofloxacin is associated with side effects, which might be reduced by improving its pharmacokinetic properties. The chemical structure of ciprofloxacin is the source of some of its limitations, which include: (1) Poor membrane permeability due to lipophobicity caused by the presence of polar groups; and (2) poor transportation and absorption due to poor water solubility caused by the flat aromatic structure. Previous methods for improving the pharmacokinetic properties of ciprofloxacin have involved the synthesis of conjugates. Issues related to poor membrane permeability, transportation and absorption of drugs can also be improved by employing nanocarriers and nanomaterials. Encapsulation within nanocarriers allows targeted drug delivery and reduced side effects as lower doses of the drug can be administered. Nanocarriers that can be used for this purpose include nanoparticles and hydrogels. Our research group is interested in supramolecular hydrogels as drug delivery systems. Short amphiphilic peptides are often able to form hydrogels through self-assembly. This present work describes the synthesis of a ciprofloxacin–dehydropeptide conjugate with the aim of forming hydrogels and related nanostructures to be used for the ‘self-delivery’ of antibacterial compounds. We assessed the hydrogelation ability, antibacterial activity, and pharmacokinetic properties. TEM microscopy revealed nanotubes and nanospheres. The conjugate was unable to form hydrogels alone but was able to form hydrogels as the major component of a co-gel with another peptide gelator. Although the conjugate retained antibacterial activity at 400 µM, activity diminished at lower concentrations. Thus, future work should focus on more hydrolysable pro-drug versions of the conjugate or versions where the peptide is connected at an alternate position.This work was supported by the Portuguese Foundation for Science and Technology (FCT) in the framework of the Strategic Funding of CQUM (UID/QUI/00686/2019). FCT, FEDER, PORTUGAL2020, and COMPETE2020 are also acknowledged for funding under research project PTDC/QUI-QOR/29015/2017 (POCI-01-0145-FEDER-029015)

Rapid Preparation of Geometrically Optimal Battery Electrode Samples for Nano Scale X-ray Characterisation

Rechargeable lithium-based batteries are one of the key enabling technologies driving the shift to renewable energy, and research into novel technologies has intensified to meet growing demands in applications requiring higher energy and power density. The mechanisms behind battery degradation can be investigated across multiple length-scales with X-ray imaging methods; at the nanoscale severe constraints are imposed on sample size in order to obtain adequate signal to noise. Here, we present a novel lasermilling technique to prepare geometrically optimal samples for X-ray nano-tomography. Advantages of this technique include significantly reduced sample preparation time, and a suitable geometry for mosaic acquisition, enabling a larger field of view to be captured at high spatial resolution, thus improving statistics. The geometry of the resulting electrode remains highly suitable for nano-tomography, and yet permits in situ and operando experiments to be carried out on standard electrode coatings, providing new insights into transient phenomena whilst closely mimicking standard electrochemical cells

A greyscale erosion algorithm for tomography (GREAT) to rapidly detect battery particle defects

Particle micro-cracking is a major source of performance loss within lithium-ion batteries, however early detection before full particle fracture is highly challenging, requiring time consuming high-resolution imaging with poor statistics. Here, various electrochemical cycling (e.g., voltage cut-off, cycle number, C-rate) has been conducted to study the degradation of Ni-rich NMC811 (LiNi0.8Mn0.1Co0.1O2) cathodes characterized using laboratory X-ray micro-computed tomography. An algorithm has been developed that calculates inter- and intra-particle density variations to produce integrity measurements for each secondary particle, individually. Hundreds of data points have been produced per electrochemical history from a relatively short period of characterization (ca. 1400 particles per day), an order of magnitude throughput improvement compared to conventional nano-scale analysis (ca. 130 particles per day). The particle integrity approximations correlated well with electrochemical capacity losses suggesting that the proposed algorithm permits the rapid detection of sub-particle defects with superior materials statistics not possible with conventional analysis

Evaluation of a model photo-caged dehydropeptide as a stimuli-responsive supramolecular hydrogel

Short peptides capped on the N-terminus with aromatic groups are often able to form supramolecular hydrogels, via self-assembly, in aqueous media. The rheological properties of these readily tunable hydrogels resemble those of the extracellular matrix (ECM) and therefore have potential for various biological applications, such as tissue engineering, biosensors, 3D bioprinting, drug delivery systems and wound dressings. We herein report a new photo-responsive supramolecular hydrogel based on a “caged” dehydropeptide (CNB-Phe-ΔPhe-OH 2), containing a photo-cleavable carboxy-2-nitrobenzyl (CNB) group. We have characterized this hydrogel using a range of techniques. Irradiation with UV light cleaves the pendant aromatic capping group, to liberate the corresponding uncaged model dehydropeptide (H-Phe-ΔPhe-OH 3), a process which was investigated by 1H NMR and HPLC studies. Crucially, this cleavage of the capping group is accompanied by dissolution of the hydrogel (studied visually and by fluorescence spectroscopy), as the delicate balance of intramolecular interactions within the hydrogel structure is disrupted. Hydrogels which can be disassembled non-invasively with temporal and spatial control have great potential for specialized on-demand drug release systems, wound dressing materials and various topical treatments. Both 2 and 3 were found to be non-cytotoxic to the human keratinocyte cell line, HaCaT. The UV-responsive hydrogel system reported here is complementary to previously reported related UV-responsive systems, which are generally composed of peptides formed from canonical amino acids, which are susceptible to enzymatic proteolysis in vivo. This system is based on a dehydrodipeptide structure which is known to confer proteolytic resistance. We have investigated the ability of the photo-activated system to accelerate the release of the antibiotic, ciprofloxacin, as well as some other small model drug compounds. We have also conducted some initial studies towards skin-related applications. Moreover, this model system could potentially be adapted for on-demand “self-delivery”, through the uncaging of known biologically active dehydrodipeptides.This work was supported by the Portuguese Foundation for Science and Technology (FCT) in the framework of the Strategic Funding of CQUM (UID/QUI/00686/2019) and of IPC (UID/CTM/50025/2019). L.H. acknowledges funding from the FCT Investigator Programme through grant IF/00606/2014. FCT, FEDER, PORTUGAL2020 and COMPETE2020 are also acknowledged for funding under research project PTDC/QUI-QOR/29015/2017 (POCI-01-0145-FEDER-029015)