A combination therapy strategy for treating antibiotic resistant biofilm infection using a guanidinium derivative and nanoparticulate Ag(0) derived hybrid gel conjugate

Bacteria organized in biofilms show significant tolerance to conventional antibiotics compared to their planktonic counterparts and form the basis for chronic infections. Biofilms are composites of different types of extracellular polymeric substances that help in resisting several host-defense measures, including phagocytosis. These are increasingly being recognized as a passive virulence factor that enables many infectious diseases to proliferate and an essential contributing facet to anti-microbial resistance. Thus, inhibition and dispersion of biofilms are linked to addressing the issues associated with therapeutic challenges imposed by biofilms. This report is to address this complex issue using a self-assembled guanidinium–Ag(0) nanoparticle (AD-L@Ag(0)) hybrid gel composite for executing a combination therapy strategy for six difficult to treat biofilm-forming and multidrug-resistant bacteria. Improved efficacy was achieved primarily through effective biofilm inhibition and dispersion by the cationic guanidinium ion derivative, while Ag(0) contributes to the subsequent bactericidal activity on planktonic bacteria. Minimum Inhibitory Concentration (MIC) of the AD-L@Ag(0) formulation was tested against Acinetobacter baumannii (25 μg mL⁻¹), Pseudomonas aeruginosa (0.78 μg mL⁻¹), Staphylococcus aureus (0.19 μg mL⁻¹), Klebsiella pneumoniae (0.78 μg mL⁻¹), Escherichia coli (clinical isolate (6.25 μg mL⁻¹)), Klebsiella pneumoniae (clinical isolate (50 μg mL⁻¹)), Shigella flexneri (clinical isolate (0.39 μg mL⁻¹)) and Streptococcus pneumoniae (6.25 μg mL⁻¹). Minimum bactericidal concentration, and MBIC₅₀ and MBIC₉₀ (Minimum Biofilm Inhibitory Concentration at 50% and 90% reduction, respectively) were evaluated for these pathogens. All these results confirmed the efficacy of the formulation AD-L@Ag(0). Minimum Biofilm Eradication Concentration (MBEC) for the respective pathogens was examined by following the exopolysaccharide quantification method to establish its potency in inhibition of biofilm formation, as well as eradication of mature biofilms. These effects were attributed to the bactericidal effect of AD-L@Ag(0) on biofilm mass-associated bacteria. The observed efficacy of this non-cytotoxic therapeutic combination (AD-L@Ag(0)) was found to be better than that reported in the existing literature for treating extremely drug-resistant bacterial strains, as well as for reducing the bacterial infection load at a surgical site in a small animal BALB/c model. Thus, AD-L@Ag(0) could be a promising candidate for anti-microbial coatings on surgical instruments, wound dressing, tissue engineering, and medical implants.

Dispersion of biofilms that protect bacteria and its subsequent killing in the planktonic state are effectively achieved by a guanidinium–Ag(0) nanocomposite.     

Improved broad-spectrum antibiotics against Gram-negative pathogens via darobactin biosynthetic pathway engineering

The development of new antibiotics is imperative to fight increasing mortality rates connected to infections caused by multidrug-resistant (MDR) bacteria. In this context, Gram-negative pathogens listed in the WHO priority list are particularly problematic. Darobactin is a ribosomally produced and post-translationally modified bicyclic heptapeptide antibiotic selectively killing Gram-negative bacteria by targeting the outer membrane protein BamA. The native darobactin A producer Photorhabdus khanii HGB1456 shows very limited production under laboratory cultivation conditions. Herein, we present the design and heterologous expression of a synthetically engineered darobactin biosynthetic gene cluster (BGC) in Escherichia coli to reach an average darobactin A production titre of 13.4 mg L⁻¹. Rational design of darA variants, encoding the darobactin precursor peptide with altered core sequences, resulted in the production of 13 new ‘non-natural’ darobactin derivatives and 4 previously hypothetical natural darobactins. One of the non-natural compounds, darobactin 9, was more potent than darobactin A, and showed significantly improved activity especially against Pseudomonas aeruginosa (0.125 μg mL⁻¹) and Acinetobacter baumannii (1–2 μg mL⁻¹). Importantly, it also displayed superior activity against MDR clinical isolates of E. coli (1–2 μg mL⁻¹) and Klebsiella pneumoniae (1–4 μg mL⁻¹). Independent deletions of genes from the darobactin BGC showed that only darA and darE, encoding a radical forming S-adenosyl-l-methionine-dependent enzyme, are required for darobactin formation. Co-expression of two additional genes associated with the BGCs in hypothetical producer strains identified a proteolytic detoxification mechanism as a potential self-resistance strategy in native producers. Taken together, we describe a versatile heterologous darobactin platform allowing the production of unprecedented active derivatives in good yields, and we provide first experimental evidence for darobactin biosynthesis processes.

Heterologous expression of a synthetically engineered darobactin gene cluster in E. coli yields new darobactin derivatives with improved anti-Gram-negative activity. Targeted gene deletions provide first insights into biosynthetic steps.     

A switchable sensor and scavenger: detection and removal of fluorinated chemical species by a luminescent metal–organic framework

Fluorosis has been regarded as a worldwide disease that seriously diminishes the quality of life through skeletal embrittlement and hepatic damage. Effective detection and removal of fluorinated chemical species such as fluoride ions (F⁻) and perfluorooctanoic acid (PFOA) from drinking water are of great importance for the sake of human health. Aiming to develop water-stable, highly selective and sensitive fluorine sensors, we have designed a new luminescent MOF In(tcpp) using a chromophore ligand 2,3,5,6-tetrakis(4-carboxyphenyl)pyrazine (H₄tcpp). In(tcpp) exhibits high sensitivity and selectivity for turn-on detection of F⁻ and turn-off detection of PFOA with a detection limit of 1.3 μg L⁻¹ and 19 μg L⁻¹, respectively. In(tcpp) also shows high recyclability and can be reused multiple times for F⁻ detection. The mechanisms of interaction between In(tcpp) and the analytes are investigated by several experiments and DFT calculations. These studies reveal insightful information concerning the nature of F⁻ and PFOA binding within the MOF structure. In addition, In(tcpp) also acts as an efficient adsorbent for the removal of F⁻ (36.7 mg g⁻¹) and PFOA (980.0 mg g⁻¹). It is the first material that is not only capable of switchable sensing of F⁻ and PFOA but also competent for removing the pollutants via different functional groups.

A robust In-MOF, In(tcpp), demonstrates sensitive detection of the fluorinated chemical species F⁻ and PFOA via distinctly different luminescence signal change, and effective adsorption and removal of both species from aqueous solution.     

An electrochemical modification strategy to fabricate NiFeCuPt polymetallic carbon matrices on nickel foam as stable electrocatalysts for water splitting

Electrochemical modification is a mild and economical way to prepare electrocatalytic materials with abundant active sites and high atom efficiency. In this work, a stable NiFeCuPt carbon matrix deposited on nickel foam (NFFeCuPt) was fabricated with an extremely low Pt load (∼28 μg cm⁻²) using one-step electrochemical co-deposition modification, and it serves as a bifunctional catalyst for overall water splitting and achieves 100 mA cm⁻² current density at a low cell voltage of 1.54 V in acidic solution and 1.63 V in alkaline solution, respectively. In addition, a novel electrolyte was developed to stabilize the catalyst under acidic conditions, which provides inspiration for the development of highly efficient, highly stable, and cost-effective ways to synthesize electrocatalysts.

Multiple metal elements immobilized into a carbon matrix to fabricate an ultra-stable water splitting electrocatalyst by one-step electrochemical modification.     

From a nanoparticular solid-state material to molecular organo-f-element-polyarsenides

A convenient pathway to new molecular organo-lanthanide-polyarsenides in general and to a f-element complex with the largest polyarsenide ligand in detail is reported. For this purpose, the activation of the solid state material As⁰_nano (nanoscale gray arsenic) by the multi electron reducing agents [K(18-crown-6)][(Ln^+II)₂(μ-η⁶:η⁶-C₆H₆)] (Ln = La, Ce, Cp′′ = 1,3-bis(trimethylsilyl)cyclopentadienyl anion) and [K(18-crown-6)]₂[(Ln^+II)₂(μ-η⁶:η⁶-C₆H₆)] (Ln = Ce, Nd) is shown. These non-classical divalent lanthanide compounds were used as three and four electron reducing agents where the product formation can be directed by variation of the applied reactant. The obtained Zintl anions As₃³⁻, As₇³⁻, and As₁₄⁴⁻ were previously not accessible in molecular 4f-element chemistry. Additionally, the corresponding compounds with As₁₄⁴⁻-moieties represent the largest organo-lanthanide-polyarsenides known to date.

Reaction of non-classical divalent lanthanide compounds with nanoparticulate gray arsenic via three- and four-electron reduction led to a series of new f-element polyarsenides, including the largest f-element polyarsenide known to date.     

Large polarization and record-high performance of energy storage induced by a phase change in organic molecular crystals

Dielectrics that undergo electric-field-induced phase changes are promising for use as high-power electrical energy storage materials and transducers. We demonstrate the stepwise on/off switching of large polarization in a series of dielectrics by flipping their antipolar or canted electric dipoles via proton transfer and inducing simultaneous geometric changes in their π-conjugation system. Among antiferroelectric organic molecular crystals, the largest-magnitude polarization jump was obtained as 18 μC cm⁻² through revisited measurements of squaric acid (SQA) crystals with improved dielectric strength. The second-best polarization jump of 15.1 μC cm⁻² was achieved with a newly discovered antiferroelectric, furan-3,4-dicarboxylic acid. The field-induced dielectric phase changes show rich variations in their mechanisms. The quadruple polarization hysteresis loop observed for a 3-(4-chlorophenyl)propiolic acid crystal was caused by a two-step phase transition with moderate polarization jumps. The ferroelectric 2-phenylmalondialdehyde single crystal having canted dipoles behaved as an amphoteric dielectric, exhibiting a single or double polarization hysteresis loop depending on the direction of the external field. The magnitude of a series of observed polarizations was consistently reproduced within the simplest sublattice model by the density functional theory calculations of dipole moments flipping over a hydrogen-bonded chain or sheet (sublattice) irrespective of compounds. This finding guarantees a tool that will deepen our understanding of the microscopic phase-change mechanisms and accelerate the materials design and exploration for improving energy-storage performance. The excellent energy-storage performance of SQA was demonstrated by both a high recoverable energy-storage density W_r of 3.3 J cm⁻³ and a nearly ideal efficiency (90%). Because of the low crystal density, the corresponding energy density per mass (1.75 J g⁻¹) exceeded those derived from the highest W_r values (∼8–11 J cm⁻³) reported for several bulk antiferroelectric ceramics , without modification to relaxor forms.

Electric-field induced phase changes, which are promising for use in high-power electrical energy storage, can be realized in a series of organic dielectrics by flipping the antipolar or canted electric dipoles via proton transfer.     

Impact of the macrocyclic structure and dynamic solvent effect on the reactivity of a localised singlet diradicaloid with π-single bonding character

Localised singlet diradicals are key intermediates in bond homolysis processes. Generally, these highly reactive species undergo radical–radical coupling reaction immediately after their generation. Therefore, their short-lived character hampers experimental investigations of their nature. In this study, we implemented the new concept of “stretch effect” to access a kinetically stabilised singlet diradicaloid. To this end, a macrocyclic structure was computationally designed to enable the experimental examination of a singlet diradicaloid with π-single bonding character. The kinetically stabilised diradicaloid exhibited a low carbon–carbon coupling reaction rate of 6.4 × 10³ s⁻¹ (155.9 μs), approximately 11 and 1000 times slower than those of the first generation of macrocyclic system (7.0 × 10⁴ s⁻¹, 14.2 μs) and the parent system lacking the macrocycle (5 × 10⁶ s⁻¹, 200 ns) at 293 K in benzene, respectively. In addition, a significant dynamic solvent effect was observed for the first time in intramolecular radical–radical coupling reactions in viscous solvents such as glycerin triacetate. This theoretical and experimental study demonstrates that the stretch effect and solvent viscosity play important roles in retarding the σ-bond formation process, thus enabling a thorough examination of the nature of the singlet diradicaloid and paving the way toward a deeper understanding of reactive intermediates.

An extremely long-lived localised singlet diradical with π-single bonding character is found in a macrocyclic structure that retards the radical–radical coupling reaction by the “stretch and solvent-dynamic effects”.     

A (μ-hydrido)diborane(4) anion and its coordination chemistry with coinage metals

A tetra(o-tolyl) (μ-hydrido)diborane(4) anion 1, an analogue of [B₂H₅]⁻ species, was facilely prepared through the reaction of tetra(o-tolyl)diborane(4) with sodium hydride. Unlike common sp²–sp³ diborane species, 1 exhibited a σ-B–B bond nucleophilicity towards NHC-coordinated transition-metal (Cu, Ag, and Au) halides, resulting in the formation of η²-B–B bonded complexes 2 as confirmed by single-crystal X-ray analyses. Compared with 1, the structural data of 2 imply significant elongations of B–B bonds, following the order Au > Cu > Ag. DFT studies show that the diboron ligand interacts with the coinage metal through a three-center-two-electron B–M–B bonding mode. The fact that the B–B bond of the gold complex is much prolonged than the related Cu and Ag compounds might be ascribed to the superior electrophilicity of the gold atom.

A tetra(o-tolyl)(μ-hydrido)diborane(4) anion is facilely prepared via the reaction of tetra(o-tolyl)diborane(4) with NaH. It exhibits a σ-B–B bond nucleophilicity towards NHC-metal halides to give the corresponding η²-B–B bonded metal complexes.     

Integration of exonuclease III-powered three-dimensional DNA walker with single-molecule detection for multiple initiator caspases assay

Initiator caspases are important components of cellular apoptotic signaling and they can activate effector caspases in extrinsic and intrinsic apoptotic pathways. The simultaneous detection of multiple initiator caspases is essential for apoptosis mechanism studies and disease therapy. Herein, we develop a sensitive nanosensor based on the integration of exonuclease III (Exo III)-powered three-dimensional (3D) DNA walker with single-molecule detection for the simultaneous measurement of initiator caspase-8 and caspase-9. This assay involves two peptide–DNA detection probe-conjugated magnetic beads and two signal probe-conjugated gold nanoparticles (signal probes@AuNPs). The presence of caspase-8 and caspase-9 can induce the cleavage of peptides in two peptide–DNA detection probes, releasing two trigger DNAs from the magnetic beads, respectively. The two trigger DNAs can serve as the walker DNA to walk on the surface of the signal probes@AuNPs powered by Exo III digestion, liberating numerous Cy5 and Texas Red fluorophores which can be quantified by single-molecule detection, with Cy5 indicating caspase-8 and Texas Red indicating caspase-9. Notably, the introduction of the AuNP-based 3D DNA walker greatly reduces the background signal and amplifies the output signals, and the introduction of single-molecule detection further improves the detection sensitivity. This nanosensor is very sensitive with a detection limit of 2.08 × 10⁻⁶ U μL⁻¹ for caspase-8 and 1.71 × 10⁻⁶ U μL⁻¹ for caspase-9, and it can be used for the simultaneous screening of caspase inhibitors and the measurement of endogenous caspase activity in various cell lines at the single-cell level. Moreover, this nanosensor can be extended to detect various proteases by simply changing the peptide sequences of the detection probes.

We demonstrate the simultaneous detection of multiple initiator caspases by integrating exonuclease III-powered three-dimensional DNA walker with single-molecule detection.     

Discovery of phosphotyrosine-binding oligopeptides with supramolecular target selectivity

We demonstrate phage-display screening on self-assembled ligands that enables the identification of oligopeptides that selectively bind dynamic supramolecular targets over their unassembled counterparts. The concept is demonstrated through panning of a phage-display oligopeptide library against supramolecular tyrosine-phosphate ligands using 9-fluorenylmethoxycarbonyl-phenylalanine-tyrosine-phosphate (Fmoc-FpY) micellar aggregates as targets. The 14 selected peptides showed no sequence consensus but were enriched in cationic and proline residues. The lead peptide, KVYFSIPWRVPM-NH₂ (P7) was found to bind to the Fmoc-FpY ligand exclusively in its self-assembled state with K_D = 74 ± 3 μM. Circular dichroism, NMR and molecular dynamics simulations revealed that the peptide interacts with Fmoc-FpY through the KVYF terminus and this binding event disrupts the assembled structure. In absence of the target micellar aggregate, P7 was further found to dynamically alternate between multiple conformations, with a preferred hairpin-like conformation that was shown to contribute to supramolecular ligand binding. Three identified phages presented appreciable binding, and two showed to catalyze the hydrolysis of a model para-nitro phenol phosphate substrate, with P7 demonstrating conformation-dependent activity with a modest k_cat/K_M = 4 ± 0.3 × 10⁻⁴ M⁻¹ s⁻¹.

Phage-display screening on self-assembled tyrosine-phosphate ligands enables the identification of oligopeptides selective to dynamic supramolecular targets, with the lead peptide showing a preferred hairpin-like conformation and catalytic activity.     

Excitation ratiometric chloride sensing in a standalone yellow fluorescent protein is powered by the interplay between proton transfer and conformational reorganization

Natural and laboratory-guided evolution has created a rich diversity of fluorescent protein (FP)-based sensors for chloride (Cl⁻). To date, such sensors have been limited to the Aequorea victoria green fluorescent protein (avGFP) family, and fusions with other FPs have unlocked ratiometric imaging applications. Recently, we identified the yellow fluorescent protein from jellyfish Phialidium sp. (phiYFP) as a fluorescent turn-on, self-ratiometric Cl⁻ sensor. To elucidate its working mechanism as a rare example of a single FP with this capability, we tracked the excited-state dynamics of phiYFP using femtosecond transient absorption (fs-TA) spectroscopy and target analysis. The photoexcited neutral chromophore undergoes bifurcated pathways with the twisting-motion-induced nonradiative decay and barrierless excited-state proton transfer. The latter pathway yields a weakly fluorescent anionic intermediate , followed by the formation of a red-shifted fluorescent state that enables the ratiometric response on the tens of picoseconds timescale. The redshift results from the optimized π–π stacking between chromophore Y66 and nearby Y203, an ultrafast molecular event. The anion binding leads to an increase of the chromophore pK_a and ESPT population, and the hindrance of conversion. The interplay between these two effects determines the turn-on fluorescence response to halides such as Cl⁻ but turn-off response to other anions such as nitrate as governed by different binding affinities. These deep mechanistic insights lay the foundation for guiding the targeted engineering of phiYFP and its derivatives for ratiometric imaging of cellular chloride with high selectivity.

We discovered an interplay between proton transfer and conformational reorganization that powers a standalone fluorescent-protein-based excitation-ratiometric biosensor for chloride imaging.     

Do carbon nanotubes catalyse bromine/bromide redox chemistry?

The redox chemistries of both the bromide oxidation and bromine reduction reactions are studied at single multi-walled carbon nanotubes (MWCNTs) as a function of their electrical potential allowing inference of the electron transfer kinetics of the Br₂/Br⁻ redox couple, widely used in batteries. The nanotubes are shown to be mildly catalytic compared to a glassy carbon surface but much less as inferred from conventional voltammetry on porous ensembles of MWCNTs where the mixed transport regime masks the true catalytic response.

Schematic of a carbon nanotube impact in bromide solution.

The bromine–bromide redox couple plays an essential role in diverse energy storage devices including hydrogen–bromine, zinc–bromine, quinone–bromine, vanadium–bromide and bromide–polysulphide flow batteries.^1–5 The Br₂/Br⁻ redox couple is attractive as a cathode reaction due to its high standard potential, large solubility of both reagents, high power density and cost efficiency.⁶ The performance of such devices is generically limited by the thermodynamics and kinetics of the redox couple comprising the battery with fast (‘reversible’) electron transfer is essential. In many cases, including the Br₂/Br⁻ couple the electrode reaction involves more than one electron as given in the stoichiometric reaction:2Br⁻ − 2e⁻ ⇄ Br₂; E⁰ = 1.08 V vs. SHEwith, at high bromide concentrations, the possibility of the follow up chemical reaction⁷Br₂ + Br⁻ ⇄ Br₃⁻Since electrons are usually transferred sequentially this implies that the mechanism is multistep with any of the individual mechanistic steps in principle being rate limiting. For this reason catalysts are commonly required to enhance the electrode kinetics at otherwise favourable electrode materials. One type of catalyst which has seen wide usage, including for the Br₂/Br⁻ couple^8,9 are carbon nanotubes (CNTs) with suggested advantages which include high surface area and the inherent porosity of CNT composites.¹⁰ The deployment of CNTs as a porous composite presents a further level of complexity to the electrode reaction beyond its multistep character because of the ill-defined mass transport within the porous layer. In particular ascertaining the intrinsic electron transfer kinetics and hence the level of catalysis, if any, is essentially impossible since these are masked in the voltammetric response by diffusional mass transport effects.^11–14 Specifically the transport within the porous structure of CNT layers is dominated by thin-layer and other^15,16 effects which give the illusion of electrochemical reversibility. In order to unscramble possible electro-catalysis of the bromine/bromide couple a different approach is needed.In the following we study both the electro-oxidation of bromide (BOR) and the electro-reduction of bromine (BRR) at single MWCNTs via ‘nano-impact (aka ‘single entity’) electrochemistry’^17–20 in aqueous solution. In this approach a micro-wire electrode at a fixed potential is inserted in a suspension of CNTs in the solution of interest. From time to time a single CNT impacts the electrode, adopts the potential of the latter for the duration of the impact which in the case of CNTs can vary from 1–100 of seconds^21–23 and sustained catalytic currents flow if the oxidation/reduction of interest is faster at the nanotube in comparison with the micro-wire electrode. The catalytic currents are studied as a function of potential revealing the electron transfer kinetics. Fig. 1 shows the concept of the experiment.Open in a separate windowFig. 1Schematic representation of ‘nano-impact’ electrochemistry on a carbon micro wire electrode for the oxidation of aqueous bromide from which the kinetics of the BOR are inferred. Analogous experiments but showing negative impact currents allow the inference of the kinetics of the BRR.The BOR and BRR were studied first, however, voltammetrically at an unmodified glassy carbon (GC) electrode as shown in Fig. 2 (black line) using 5.0 mM solutions of either NaBr or Br₂ in 0.1 M HNO₃. The midpoint potential was 0.82 V versus the saturated calomel electrode (SCE) consistent with the literature values for the formal potential of the Br₂/Br⁻ couple.²⁴ The voltammograms were analysed to give transfer coefficients of 0.45 ± 0.01 and 0.33 ± 0.01 (ESI, Section 2^†) for the BOR and BRR respectively. Both processes were inferred to be diffusional and the diffusion coefficients D_Br⁻ and D_Br2 were calculated to be 2.05 (±0.04) × 10⁻⁵ cm² s⁻¹ and 1.50 (±0.04) × 10⁻⁵ cm² s⁻¹ (ESI, Section 3^†) using the Randles–Ševčík equation for an irreversible reaction the values are consistent with literature reports.²⁴ Then the electrodes were modified with 30 μg of MWCNTs consisting of ca. 125 monolayers (the calculation is given in the ESI, Section 9^†) of MWCNTs assuming that they are closely packed across the area of the GC electrode, and the resulting voltammograms are shown in Fig. 2 (red line). In comparison with the unmodified electrode, enhanced currents are seen for the Br₂/Br⁻ couple which partly reflects the enhanced capacitance of the interface reflecting in turn the large surface area of the deposited nanotubes (ca. 60–120 cm²). Larger signals are also seen indicating a thin layer contribution from the material occluded within the porous layer which also leads to the apparently quasi-reversible shape of the voltammograms obtained for both reactions. A log–log plot of peak current (I_p) vs. scan rate (ν) showed a gradient value of 0.68 (±0.01) and 0.66 (±0.03) for the BOR and BRR (ESI, Section 4^†) confirming a mixed mass transport regime^12,14 with a combination of semi-infinite diffusion and thin layer behaviour. The transition from the fully irreversible to the apparent quasi-reversible character is sometimes confused with electro-catalysis attributed to the CNTs rather than thin-layer diffusion. In order to ascertain the true catalytic response, single entity electrochemistry was measured to obtain the BOR and BRR responses at single CNTs.Open in a separate windowFig. 2Cyclic voltammograms at pristine GC (black line) and 30 μg MWCNTs dropcast on GC (red line) at a scan rate of 0.05 V s⁻¹ (a) for the bromide oxidation reaction (BOR) in 5.0 mM NaBr in 0.1 M HNO₃, (b) for the bromine reduction reaction (BRR) in 5.0 mM bromine in 0.1 M HNO₃.For single entity measurements, a clean carbon wire (CWE, length 1 mm and diameter 7 μm) working electrode was used. Chronoamperograms were recorded at a constant applied potential of 0.2 V vs. SCE and 1.3 V vs. SCE for the BOR and BRR respectively (5.0 mM solutions). These values were selected in the light of Fig. 2 to provide a large overpotential for each reaction. Clear oxidative and reductive current steps were observed (Fig. 3). These were ascribed to the arrival of a MWCNT at the electrode surface and the resulting catalytic electron transfer for the duration of the impact. No steps were observed in the absence of MWCNTs (ESI, Fig. S4^†). The average residence time of the MWCNT was 1.2 (±0.5) seconds and the frequency of the collisions was 0.3 (±0.1) impacts per second. The average impact current for the BOR at 1.3 V vs. SCE was 2.8 (±0.2) nA (65 impacts) and for the BRR at 0.2 V vs. SCE it was 3.8 (±0.1) nA (70 impacts). The impact currents were assumed to be entirely faradaic since control experiments in 0.1 M HNO₃ solution in the presence of 100 μg of MWCNTs (in the absence of Br⁻ and Br₂) showed no obvious impacts as shown in ESI Section 10.^†Open in a separate windowFig. 3Chronoamperograms showing the impact step current (a) for the BOR in 5.0 mM NaBr in 0.1 M HNO₃ at 1.3 V vs. SCE, (b) for the BRR in 5.0 mM bromine in 0.1 M HNO₃ at 0.2 V vs. SCE.Further, impacts for both the BOR and BRR were observed at various potentials (ESI, Section 11^†) and analysed to obtain the average faradaic current at each potential. The average impact step current was plotted against the applied potential (Fig. 4). Two sigmoidal curves were obtained reflecting the current–potential response for either the bromide oxidation (BOR) or the bromine reduction (BRR). The curves reflect the average voltammograms (current–potential characteristics) for the Br₂/Br⁻ redox reaction at single carbon nanotubes. The shape of the two sigmoidal curves reflects the onset of electrolysis followed by a diffusion controlled plateau at high over-potentials.²⁵ Mass transport corrected Tafel analysis (Fig. 4; inset) showed the transfer coefficients β to be ca. 0.42 and α to be ca. 0.20 from the impacts for the BOR and BRR respectively (ESI, Section 6^†). The length distribution of the MWCNTs was calculated (ESI, Section 6^†) from the currents recorded at potentials corresponding to the plateau in Fig. 4 assuming that the reactions are (Fickian) diffusion controlled at the potentials used and by modelling the CNTs as cylindrical electrodes²¹ assuming a nanotube radius of 15 (±5) nm and the diffusion coefficients reported above. Chronoamperometry was also conducted for the BOR and BRR in the absence of MWCNTs at 1.3 V and 0.2 V vs. SCE respectively to confirm that no impact currents were contributed by the redox species in the electrolyte (ESI, Section 5^†). Alongside, chronoamperograms in 0.1 M HNO₃ and 100 μg show that the impact current was contributed only by the Br⁻ and Br₂ redox reaction and the results are shown in the ESI, Section 10.^†Open in a separate windowFig. 4Average step currents observed as a function of applied potential (a) for the BOR in 5.0 mM NaBr in 0.1 M HNO₃ at, (b) for the BRR in 5.0 mM Bromine in 0.1 M HNO₃; insets in both the cases show mass transport corrected Tafel analyses.The lengths were found to be 5.4 (±3.4) μm (BOR) and 5.9 (±1.3) μm (BRR) and are given in Fig. 5 (see ESI, Section 7^† for calculations). These values were compared with previously reported dark-field optical microscopy data and good agreement was observed with the literature value of 5.3 (±2.1) μm.²⁶ The observed consistency provides strong support for the choice of modelling the single entity voltammetry by analogy with that of a cylindrical electrode.Open in a separate windowFig. 5The length of MWCNTs calculated from the impact currents for the BOR (at 1.3 V vs. SCE) and BRR (at 0.2 V vs. SCE).It is evident that the single entity measurements allow a clear analysis of the catalytic behaviour of the carbon nanotubes by providing a well-defined diffusional regime conducive to the extraction of the electrode kinetics of both the bromide oxidation and the bromine reduction process. In contrast, electrodes were formed by ensembles of carbon nanotubes in the form of a porous layer where the mixed transport regime is not amenable to ready modelling and the dissection of thin-layer effects from the measured voltammetry. The electron transfer kinetics for both the BOR and BRR at single MWCNTs was then obtained via full simulation of the two single entity ‘voltammograms’ using the above measured diffusion coefficients and again treating the impacted MWCNT as a cylindrical electrode with uniform diffusional access and further assuming Butler–Volmer kinetics. For the BOR, one electron transfer was considered as given below,For the BRR the two electron transfer was modelled as,Br₂ + 2e⁻ → 2Br⁻The set of parameters used for the analysis are given in the ESI, Section 8.^† By using the transfer coefficients deduced from Fig. 4, the only unknown is the standard electrochemical rate constant k which is determined by fitting the impact voltammogram measured relative to a formal potential for the Br₂/Br⁻ couple of 0.82 V vs. SCE obtained from the voltammogram at pristine GC. Fig. 6 shows the fitting for the BOR and the BRR with rate constants k_BOR of 1.0 (±0.1) × 10⁻³ cm s⁻¹ and k_BRR of 5.0 (±0.1) × 10⁻⁴ cm s⁻¹ respectively. The transfer coefficients and rate constants obtained from impacts were compared to the voltammograms obtained at pristine GC for the BOR and BRR and are given in Open in a separate windowFig. 6DIGISIM simulated curves (black line) for average impact currents obtained at different potentials (red circles) (a) for the BOR with a rate constant (k_BOR) of 1.0 (±0.1) × 10⁻³ cm s⁻¹; (b) BRR with a k_BRR of 5.0 (±0.1) × 10⁻⁴ cm s⁻¹.Transfer coefficients and rate constants for the BOR in 5.0 mM NaBr in 0.1 M HNO₃ and the BRR in 5.0 mM bromine in 0.1 M HNO₃ obtained at the glassy carbon macroelectrode GC, and single MWCNT impact current

Dandelion flower-like micelles

Dandelion flower-like micelles (DFMs) were prepared by self-assembly of polycaprolactone (PCL) functionalized surface cross-linked micelles (SCMs). Upon reductive stimuli, the SCMs can be released from the DFMs by non-Brownian motion at an average speed of 19.09 μm s⁻¹. Similar to the property of dandelion flowers dispersing their seeds over a long distance, the DFMs demonstrated enhanced multicellular tumor spheroid (MTS) penetration, a useful property in the treatment of many diseases including cancer, infection-of-biofilm diseases and ocular problems.

Dandelion flower-like micelles (DFMs) can release surface cross-linked micelles (SCMs) by non-Brownian motion at an average speed of 19.09 μm s⁻¹ upon reductive stimuli.     

Light Intensity and Photoperiod Affect Growth and Nutritional Quality of Brassica Microgreens

We explored the effects of different light intensities and photoperiods on the growth, nutritional quality and antioxidant properties of two Brassicaceae microgreens (cabbage Brassica oleracea L. and Chinese kale Brassica alboglabra Bailey). There were two experiments: (1) four photosynthetic photon flux densities (PPFD) of 30, 50, 70 or 90 μmoL·m⁻²·s⁻¹ with red:blue:green = 1:1:1 light-emitting diodes (LEDs); (2) five photoperiods of 12, 14, 16, 18 or 20 h·d⁻¹. With the increase of light intensity, the hypocotyl length of cabbage and Chinese kale microgreens shortened. PPFD of 90 μmol·m⁻²·s⁻¹ was beneficial to improve the nutritional quality of cabbage microgreens, which had higher contents of chlorophyll, carotenoids, soluble sugar, soluble protein and vitamin C, as well as increased antioxidant capacity. The optimal PPFD for Chinese kale microgreens was 70 μmol·m⁻²·s⁻¹. Increasing light intensity could increase the antioxidant capacity of cabbage and Chinese kale microgreens, while not significantly affecting glucosinolate (GS) content. The dry and fresh weight of cabbage and Chinese kale microgreens were maximized with a 14-h·d⁻¹ photoperiod. The chlorophyll, carotenoid and soluble protein content in cabbage and Chinese kale microgreens were highest for a 16-h·d⁻¹ photoperiod. The lowest total GS content was found in cabbage microgreens under a 12-h·d⁻¹ photoperiod and in Chinese kale microgreens under 16-h·d⁻¹ photoperiod. In conclusion, the photoperiod of 14~16 h·d⁻¹, and 90 μmol·m⁻²·s⁻¹ and 70 μmol·m⁻²·s⁻¹ PPFD for cabbage and Chinese kale microgreens, respectively, were optimal for cultivation.     

Low power threshold photochemical upconversion using a zirconium(iv) LMCT photosensitizer

The current investigation demonstrates highly efficient photochemical upconversion (UC) where a long-lived Zr(iv) ligand-to-metal charge transfer (LMCT) complex serves as a triplet photosensitizer in concert with well-established 9,10-diphenylanthracene (DPA) along with newly conceived DPA–carbazole based acceptors/annihilators in THF solutions. The initial dynamic triplet–triplet energy transfer (TTET) processes (ΔG ∼ −0.19 eV) featured very large Stern–Volmer quenching constants (K_SV) approaching or achieving 10⁵ M⁻¹ with bimolecular rate constants between 2 and 3 × 10⁸ M⁻¹ s⁻¹ as ascertained using static and transient spectroscopic techniques. Both the TTET and subsequent triplet–triplet annihilation (TTA) processes were verified and throughly investigated using transient absorption spectroscopy. The Stern–Volmer metrics support 95% quenching of the Zr(iv) photosensitizer using modest concentrations (0.25 mM) of the various acceptor/annihilators, where no aggregation took place between any of the chromophores in THF. Each of the upconverting formulations operated with continuous-wave linear incident power dependence (λ_ex = 514.5 nm) down to ultralow excitation power densities under optimized experimental conditions. Impressive record-setting η_UC values ranging from 31.7% to 42.7% were achieved under excitation conditions (13 mW cm⁻²) below that of solar flux integrated across the Zr(iv) photosensitizer''s absorption band (26.7 mW cm⁻²). This study illustrates the importance of supporting the continued development and discovery of molecular-based triplet photosensitizers based on earth-abundant metals.

The LMCT photosensitizer Zr(^MesPDP^Ph)₂ paired with DPA-based acceptors enabled low power threshold photochemical upconversion with record-setting quantum efficiencies.     

The smallest 4f-metalla-aromatic molecule of cyclo-PrB2− with Pr–B multiple bonds

The concept of metalla-aromaticity proposed by Thorn–Hoffmann (Nouv. J. Chim. 1979, 3, 39) has been expanded to organometallic molecules of transition metals that have more than one independent electron-delocalized system. Lanthanides, with highly contracted 4f atomic orbitals, are rarely found in multiply aromatic systems. Here we report the discovery of a doubly aromatic triatomic lanthanide-boron molecule PrB₂⁻ based on a joint photoelectron spectroscopy and quantum chemical investigation. Global minimum structural searches reveal that PrB₂⁻ has a C_2v triangular structure with a paramagnetic triplet ³B₂ electronic ground state, which can be viewed as featuring a trivalent Pr(III,f²) and B₂⁴⁻. Chemical bonding analyses show that this cyclo-PrB₂⁻ species is the smallest 4f-metalla-aromatic system exhibiting σ and π double aromaticity and multiple Pr–B bonding characters. It also sheds light on the formation of the rare B₂⁴⁻ tetraanion by the high-lying 5d orbitals of the 4f-elements, completing the isoelectronic B₂⁴⁻, C₂²⁻, N₂, and O₂²⁺ series.

We report the smallest 4f-metalla-aromatic molecule of PrB₂⁻ exhibiting σ and π double aromaticity and multiple Pr–B bond characters.     

Chain end-group selectivity using an organometallic Al(iii)/K(i) ring-opening copolymerization catalyst delivers high molar mass,monodisperse polyesters

Polyesters are important plastics, elastomers and fibres; efficient and selective polymerizations making predictable, high molar mass polymers are required. Here, a new type of catalyst for the ring-opening polymerization (ROCOP) of epoxides and anhydrides combines unusually high chain end-group selectivity, fast rates, and good molar mass control. The organometallic heterodinuclear Al(iii)/K(i) complex, applied with a diol, is tolerant to a range of epoxides/phthalic anhydride and produces only α,ω-hydroxyl telechelic polyesters with molar masses from 6–91 kg mol⁻¹, in all cases with monomodal distributions. As proof of its potential, high molar mass poly(vinyl cyclohexene oxide-alt-phthalic anhydride) (91 kg mol⁻¹) shows 5× greater flexural strain at break (ε_b = 3.7%) and 9× higher maximum flexural stress (σ_f = 72.3 MPa) than the previously accessed medium molar mass samples (24 kg mol⁻¹). It is also enchains phthalic anhydride, vinyl cyclohexene oxide and ε-decalactone, via switchable catalysis, to make high molar mass triblock polyesters (81 kg mol⁻¹, Đ = 1.04). This selective catalyst should be used in the future to qualify the properties of these ROCOP polyesters and to tune (multi)block polymer structures.

A heterodinuclear Al(iii)/K(i) organometallic ring-opening copolymerization catalyst shows exceptional rates, end-group selectivity and good loading tolerance to deliver monodisperse polyesters with molar masses up to 91 kg mol⁻¹.     

A small-molecule organic ferroelectric with piezoelectric voltage coefficient larger than that of lead zirconate titanate and polyvinylidene difluoride

Piezoelectric materials that generate electricity when deforming are ideal for many implantable medical sensing devices. In modern piezoelectric materials, inorganic ceramics and polymers are two important branches, represented by lead zirconate titanate (PZT) and polyvinylidene difluoride (PVDF). However, PVDF is a nondegradable plastic with poor crystallinity and a large coercive field, and PZT suffers from high sintering temperature and toxic heavy element. Here, we successfully design a metal-free small-molecule ferroelectric, 3,3-difluorocyclobutanammonium hydrochloride ((3,3-DFCBA)Cl), which has high piezoelectric voltage coefficients g₃₃ (437.2 × 10⁻³ V m N⁻¹) and g₃₁ (586.2 × 10⁻³ V m N⁻¹), a large electrostriction coefficient Q₃₃ (about 4.29 m⁴ C⁻²) and low acoustic impedance z₀ (2.25 × 10⁶ kg s⁻¹ m⁻²), significantly outperforming PZT (g₃₃ = 34 × 10⁻³ V m N⁻¹ and z₀ = 2.54 × 10⁷ kg s⁻¹ m⁻²) and PVDF (g₃₃ = 286.7 × 10⁻³ V m N⁻¹, g₃₁ = 185.9 × 10⁻³ V m N⁻¹, Q₃₃ = 1.3 m⁴ C⁻², and z₀ = 3.69 × 10⁶ kg s⁻¹ m⁻²). Such a low acoustic impedance matches that of the body (1.38–1.99 × 10⁶ kg s⁻¹ m⁻²) reasonably well, making it attractive as next-generation biocompatible piezoelectric devices for health monitoring and “disposable” invasive medical ultrasound imaging.

A small-molecule organic ferroelectric (3,3-DFCBA)Cl has high piezoelectric voltage coefficients g₃₃ (437.2 × 10⁻³ V m N⁻¹), a large electrostriction coefficient Q₃₃, and low acoustic impedance z₀, far beyond that of PZT and PVDF.     

A general strategy for the synthesis of α-trifluoromethyl- and α-perfluoroalkyl-β-lactams via palladium-catalyzed carbonylation

β-Lactam compounds play a key role in medicinal chemistry, specifically as the most important class of antibiotics. Here, we report a novel one-step approach for the synthesis of α-(trifluoromethyl)-β-lactams and related products from fluorinated olefins, anilines and CO. Utilization of an advanced palladium catalyst system with the Ruphos ligand allows for selective cycloaminocarbonylations to give diverse fluorinated β-lactams in high yields.

β-Lactam compounds play a key role in medicinal chemistry, specifically as the most important class of antibiotics.     

High-yield and sustainable synthesis of quinoidal compounds assisted by keto–enol tautomerism

The classical synthesis of quinoids, which involves Takahashi coupling and subsequent oxidation, often gives only low to medium yields. Herein, we disclose the keto–enol-tautomerism-assisted spontaneous air oxidation of the coupling products to quinoids. This allows for the synthesis of various indandione-terminated quinoids in high isolated yields (85–95%). The origin of the high yield and the mechanism of the spontaneous air oxidation were ascertained by experiments and theoretical calculations. All the quinoidal compounds displayed unipolar n-type transport behavior, and single crystal field-effect transistors based on the micro-wires of a representative quinoid delivered an electron mobility of up to 0.53 cm² V⁻¹ s⁻¹, showing the potential of this type of quinoid as an organic semiconductor.

Facilitated by the highly efficient Pd-catalyzed coupling and keto–enol-tautomerism-assisted spontaneous air oxidation, various indandione-terminated quinoidal compounds have been synthesized in isolated yields up to 95%.