Potential-Modulated Ion Distributions in the Back-to-Back Electrical Double Layers at a Polarised Liquid|Liquid Interface Regulate the Kinetics of Interfacial Electron Transfer

Biphasic interfacial electron transfer (IET) reactions at polarisable liquid|liquid (L|L) interfaces underpin new approaches to electrosynthesis, redox electrocatalysis, bioelectrochemistry and artificial photosynthesis. Herein, using cyclic and alternating current voltammetry, we demonstrate that under certain experimental conditions, the biphasic 2-electron O2 reduction reaction can proceed by single-step IET between a reductant in the organic phase, decamethylferrocene, and interfacial protons in the presence of O2. Using this biphasic system, we demonstrate that the applied interfacial Galvani potential difference ΔwoØ provides no direct driving force to realise a thermodynamically uphill biphasic IET reaction in the mixed solvent region. We show that the onset potential for a biphasic single-step IET reaction does not correlate with the thermodynamically predicted standard Galvani IET potential and is instead closely correlated with the potential of zero charge at a polarised L|L interface. We outline that the applied ΔwoØ required to modulate the interfacial ion distributions, and thus kinetics of IET, must be optimised to ensure that the aqueous and organic redox species are present in substantial concentrations at the L|L interface simultaneously in order to react.M.D.S. acknowledges funding from Science Foundation Ireland (SFI) under grant no. 13/SIRG/2137 and the European Research Council through a Starting Grant (agreement no. 716792). A.G.-Q. acknowledges funding received from an Irish Research Council (IRC) Government of Ireland Postdoctoral Fellowship Award (grant number GOIPD/2018/252) and a Marie Skłodowska-Curie Postdoctoral Fellowship (Grant Number MSCA-IF-EF-ST 2020/101018277)

Investigation of modified nanopore arrays using FIB/SEM tomography

The investigation of electrochemical processes at the interface of two immiscible electrolyte solutions (ITIES) is of great interest for sensing applications, and serves as a surrogate to the study of biological transport phenomena, e.g. ion channels. Alongside e-beam lithography, focused ion beam (FIB) milling is an attractive method to prototype and fabricate nanopore arrays that support nanoITIES. Within this contribution, we explore the capability of FIB/scanning electron microscopy (SEM) tomography to visualize the actual pore structure and interfaces at silica-modified nanoporous membranes. The nanopores were also characterized by atomic force microscopy (AFM) using ultra-sharp AFM probes to determine the pore diameter, and using scanning transmission electron microscopy (STEM) and energy dispersive X-ray (EDX) spectroscopy, providing additional information on the elemental composition of deposits within the pores. Si-rich particles could be identified within the pores as well as at the orifice that had faced the organic electrolyte solution during electrochemical deposition. The prospects of the used techniques for investigating the interface at or within FIB-milled nanopores will be discussed

Visualization of Diffusion within Nanoarrays

The direct experimental characterization of diffusion processes at nanoscale remains a challenge that could help elucidate processes in biology, medicine and technology. In this report, two experimental approaches were employed to visualize ion diffusion profiles at the orifices of nanopores (radius (ra) of 86 ± 6 nm) in array format: (1) electrochemically assisted formation of silica deposits based on surfactant ion transfer across nanointerfaces between two immiscible electrolyte solutions (nanoITIES); (2) combined atomic force - scanning electrochemical microscopy (AFM-SECM) imaging of topography and redox species diffusion through the nanopores. The nature of the diffusion zones formed around the pores is directly related to the interpore distance within the array. Nanopore arrays with different ratios of pore center-to-center separation (rc) to pore radius (ra) were fabricated by focused ion beam (FIB) milling of silicon nitride (SiN) membranes, with 100 pores in a hexagonal arrangement. The ion diffusion profiles determined by the two visualization methods indicated the formation of overlapped or independent diffusion profiles at nanopore arrays with rc/ra ratios of 21 ± 2 and 91 ± 7, respectively. In particular, the silica deposition method resulted in formation of a single deposit encompassing the complete array with closer nanopore arrangement, whereas individual silica deposits were formed around each nanopore within the more widely spaced array. The methods reveal direct experimental evidence of diffusion zones at nanopore arrays and provide practical illustration that the pore-pore separation within such arrays has a significant impact on diffusional transport as the pore size is reduced to the nanoscale. These approaches to nanoscale diffusion zone visualization open up possibilities for better understanding of molecular transport processes within miniaturized systems

Modulation of the silica sol-gel composition for the promotion of direct electron transfer to encapsulated cytochrome

The direct electron transfer between indium-tin oxide electrodes (ITO) and cytochrome c encapsulated in different sol-gel silica networks was studied. Cyt c@silica modified electrodes were synthesized by a two-step encapsulation method mixing a phosphate buffer solution with dissolved cytochrome c and a silica sol prepared by the alcohol-free sol-gel route. These modified electrodes were characterized by cyclic voltammetry, UV-vis spectroscopy, and in situ UV-vis spectroelectrochemistry. The electrochemical response of encapsulated protein is influenced by the terminal groups of the silica pores. Cyt c does not present electrochemical response in conventional silica (hydroxyl terminated) or phenyl terminated silica. Direct electron transfer to encapsulated cytochrome c and ITO electrodes only takes place when the protein is encapsulated in methyl modified silica networks.We gratefully acknowledge Jesus Yanez and Prof. Jose Miguel Martin-Martinez from the Laboratory of Adhesion and Adhesives (University of Alicante) for their assistance in the measurements of contact angle. We also acknowledge the Financial support from the Spanish Ministerio de Economia y Competitividad and FEDER y Ciencia (MAT2010-15273), Generalitat Valenciana (PROMETEO2013/038), and the Fundacion Ramon Areces (CIVP16A1821). Alonso Gamero-Quijano is grateful to Generalitat Valenciana (Santiago Grisolia Program) for the funding of his research fellowship.Gamero-Quijano, A.; Huerta, F.; Morallón, E.; Montilla, F. (2014). Modulation of the silica sol-gel composition for the promotion of direct electron transfer to encapsulated cytochrome. Langmuir. 30(34):10531-10538. https://doi.org/10.1021/la5023517S1053110538303

Safety and efficacy of intra-arterial bone marrow mononuclear cell transplantation in patients with acute ischaemic stroke in Spain (IBIS trial): a phase 2, randomised, open-label, standard-of-care controlled, multicentre trial

[Background] Pilot clinical trials have shown the safety of intra-arterial bone marrow mononuclear cells (BMMNCs) in stroke. However, the efficacy of different doses of intra-arterial BMMNCs in patients with acute stroke has not been tested in a randomised clinical trial. We aimed to show safety and efficacy of two different doses of autologous intra-arterial BMMNC transplantation in patients with acute stroke.[Methods] The IBIS trial was a multicentre phase 2, randomised, controlled, investigator-initiated, assessor-blinded, clinical trial, in four stroke centres in Spain. We included patients (aged 18–80 years) with a non-lacunar, middle cerebral artery ischaemic stroke within 1–7 days from stroke onset and with a National Institutes of Health Stroke Scale score of 6–20. We randomly assigned patients (2:1:1) with a computer-generated randomisation sequence to standard of care (control group) or intra-arterial injection of autologous BMMNCs at one of two different doses (2 × 106 BMMNCs/kg or 5 × 106 BMMNCs/kg). The primary efficacy outcome was the proportion of patients with modified Rankin Scale scores of 0–2 at 180 days in the intention-to-treat population, comparing each BMMNC dose group and the pooled BMMNC group versus the control group. The primary safety endpoint was the proportion of serious adverse events. This trial was registered at ClinicalTrials.gov, NCT02178657 and is completed.[Findings] Between April 1, 2015, and May 20, 2021, we assessed 114 patients for eligibility. We randomly assigned 77 (68%) patients: 38 (49%) to the control group, 20 (26%) to the low-dose BMMNC group, and 19 (25%) the high-dose BMMNC group. The mean age of participants was 62·4 years (SD 12·7), 46 (60%) were men, 31 (40%) were women, all were White, and 63 (82%) received thrombectomy. The median NIHSS score before randomisation was 12 (IQR 9–15), with intra-arterial BMMNC injection done a median of 6 days (4–7) after stroke onset. The primary efficacy outcome occurred in 14 (39%) patients in the control group versus ten (50%) in the low-dose group (adjusted odds ratio 2·08 [95% CI 0·55–7·85]; p=0·28), eight (44%) in the high-dose group (1·89 [0·52–6·96]; p=0·33), and 18 (47%) in the pooled BMMNC group (2·22 [0·72–6·85]; p=0·16). We found no differences in the proportion of patients who had adverse events or dose-related events, but two patients had a groin haematoma after cell injection in the low-dose BMMNC group.[Interpretation] Intra-arterial BMMNCs were safe in patients with acute ischaemic stroke, but we found no significant improvement at 180 days on the mRS. Further clinical trials are warranted to investigate whether improvements might be possible at different timepoints.The Andalusian Network for the Design and Translation of Advanced Therapies through the Andalusian Progress and Health Public Foundation is the study sponsor. We acknowledge all the participants of the trial and the investigators. We thank the funding bodies Instituto de Salud Carlos III through the projects PI18/01414, PI15/01197, RD16/0019/0015 (INVICTUS+), and RD21/0006/0015 (co-funded by the European Regional Development Fund “A way to make Europe” and by the European Social Fund [FSE] “The FSE invests in your future”), Mutua Madrileña grant, and the Regional Ministry of Health of Andalusia, who financed the costs incurred by participating hospitals and the Andalusian Network for the Design and Translation of Advanced Therapies through the Andalusian Progress and Health Public Foundation. MM-R has a Rio Hortega grant (CM21/00096). We acknowledge the Methodological and Statistical Support Unit from the Andalusian Public Foundation for Health Research Management in Seville (FISEVI) for their support in the statistical analysis.Peer reviewe

Mechanistic Insights into the Potentiodynamic Electrosynthesis of PEDOT Thin Films at a Polarisable Liquid|Liquid Interface

Conducting polymer (CP) thin films find widespread use, for example in bioelectronic, energy harvesting and storage, and drug delivery technology. Electrosynthesis at a polarisable liquid|liquid interface using an aqueous oxidant and organic soluble monomer provides a route to free-standing and scalable CP thin films, such as poly(3,4-ethylenedioxythiophene) (PEDOT), in a single step at ambient conditions. Here, using the potentiodynamic technique of cyclic voltammetry, interfacial electrosynthesis involving ion-exchange, electron transfer, and proton adsorption charge transfer processes is shown to be mechanistically distinct from CP electropolymerisation at a solid electrode|electrolyte interface. The applied interfacial Galvani potential difference controls the interfacial concentration of the oxidant, EDOT monomers and oligomers, but not the CP redox state. Nevertheless, typical CP electropolymerisation electrochemical behaviours, such as steady charge accumulation with each successive cycle and the appearance of a nucleation loop, were observed. By combining (spectro)electrochemical measurements and theoretical models, this work identifies the underlying mechanistic origin of each feature on the cyclic voltammograms (CVs) due to charge accumulated from Faradaic and capacitive processes as the PEDOT thin film grows. The experimental methodology and theoretical models outlined in this article provide a broadly generic framework to understand evolving CVs during interfacial electrosynthesis using any suitable oxidant/monomer combination

Electrochemical behaviour of PSS-Functionalized silica films prepared by electroassisted deposition of Sol-Gel precursors

Porous, electrically insulating SiO2 layers containing polystyrene sulfonate (PSS) were deposited on glassy carbon electrodes by an electrochemically assisted deposition method. The obtained material was characterized by microscopic, spectroscopic and thermal techniques. Silica-PSS films modify the electrochemical response of the glassy carbon electrodes against selected redox probes. Positively charged species show reduced diffusivities across the SiO2-PSS pores, which resulted in a concentration ratio higher than 1 for these species. The opposite behaviour was found for negatively charged redox probes. These observations can be interpreted in terms of the different affinity of the GC/SiO2-PSS-modified electrode for the electroactive species, as a consequence of the negatively charged porous silica.Financial support from the Spanish Ministerio de Economia y Competitividad and FEDER (MAT2010-15273) and Fundacion Ramon Areces is gratefully acknowledged. Financial support from the Generalitat Valenciana is acknowledged (PROMETEO2013/038). A.G.Q. thanks go to Generalitat Valenciana for a Santiago Grisolia grant. D.S.T. thanks Spanish Ministerio de Economia y Competitividad for an FPI grant (BES-2010-035238).Gamero-Quijano, A.; Huerta, F.; Salinas-Torres, D.; Morallón, E.; Montilla, F. (2015). Electrochemical behaviour of PSS-Functionalized silica films prepared by electroassisted deposition of Sol-Gel precursors. Electrocatalysis. 6(1):33-41. https://doi.org/10.1007/s12678-014-0215-0S334161R. Gangopadhyay, A. De, Chem. Mater. 12, 608 (2000)J.J. Gooding, Electrochim. Acta 50, 3049 (2005)M.M. Collinson, A.R. Howells, Anal. Chem. 72, 702 (2000)G.W.S.C. Jeffrey Brinker, Sol–gel Science: the Physics and Chemistry of Sol–gel Prcessing (Academid Press Limited, San Diego, 1990)A.G. Mayes, K. Mosbach, TrAC, Trends Anal. Chem. 16, 321 (1997)A. Bossi, F. Bonini, A.P.F. Turner, S.A. Piletsky, Biosens. Bioelectron. 22, 1131 (2007)A. Walcarius, Electroanalysis 13, 701 (2001)A. Katz, M.E. Davis, Nature 403, 286 (2000)C.W. Jones, K. Tsuji, M.E. Davis, Nature 393, 52 (1998)A. Walcarius, Chem. Mater. 13, 3351 (2001)A. Walcarius, Electroanalysis 10, 1217 (1998)S. Lowell, J.E. Shields, M.A. Thomas, M. Thommes, Characterization of Porous Solids and Powders: Surface Area, Pore Size and Density (Kluwer Academic Publishers, Dordrecht, 2006)D. Cazorla-Amorós, J. Alcañiz-Monge, A. Linares-Solano, Langmuir 12, 2820 (1996)D. Cazorla-Amorós, J. Alcañiz-Monge, M.A. Casa-Lillo, A. Linares-Solano, Langmuir 14, 4589 (1998)R. Esquembre, J.A. Poveda, C.R. Mateo, J. Phys. Chem. B 113, 7534 (2009)U. Hanefeld, L. Gardossi, E. Magner, Chem. Soc. Rev. 38, 453 (2009). Y1 - 2009///D. Salinas-Torres, F. Montilla, F. Huerta, E. Morallón, Electrochim. Acta 56, 3620 (2011)O. Lev, Z. Wu, S. Bharathi, V. Glezer, A. Modestov, J. Gun, L. Rabinovich, S. Sampath, Chem. Mater. 9, 2354 (1997)R. Shacham, D. Avnir, D. Mandler, Adv. Mater. 11, 384 (1999)M. Sheffer, A. Groysman, D. Mandler, Corros. Sci. 45, 2893 (2003)G.H.A. Therese, P.V. Kamath, Chem. Mater. 12, 1195 (2000)A. Gamero-Quijano, F. Huerta, D. Salinas-Torres, E. Morallón, F. Montilla, Electrocatalysis 1 (2013)M. Muroya, Colloids Surf., A 157, 147 (1999)J.R. Martinez, F. Ruiz, Y.V. Vorobiev, F. Perez-Robles, J. Gonzalez-Hernandez, J. Chem. Phys. 109, 7511 (1998)P. Innocenzi, J. Non-Cryst. Solids 316, 309 (2003)E.B. Orler, D.J. Yontz, R.B. Moore, Macromolecules 26, 5157 (1993)J.C. Yang, M.J. Jablonsky, J.W. Mays, Polymer 43, 5125 (2002)N.M. Reynolds, J.D. Savage, S.L. Hsu, Macromolecules 22, 2867 (1989)N. Ishihara, T. Seimiya, M. Kuramoto, M. Uoi, Macromolecules 19, 2464 (1986)C. Barbero, J.J. Silber, L. Sereno, J. Electroanal. Chem. Interfacial. Electrochem. 248, 321 (1988)M. Etienne, A. Quach, D. Grosso, L. Nicole, C.M. Sanchez, A. Walcarius, Chem. Mater. 19, 844 (2007)V. Ganesan, A. Walcarius, Langmuir 20, 3632 (2004)M.D. Petit-Dominguez, H. Shen, W.R. Heineman, C.J. Seliskar, Anal. Chem. 69, 703 (1997)R.S. Nicholson, Anal. Chem. 37, 1351 (1965)E. Mahe, D. Devilliers, C. Comninellis, Electrochim. Acta 50, 2263 (2005)H. Matsuda, Y. Ayabe, Z. Elektrochemie. 59, 494 (1955)A.J. Bard, L.R. Faulkner, Electrochemical Methods: Fundamentals and Applications (Wiley, New York, 1980)D.J. Dickson, B. Lassetter, B. Glassy, C.J. Page, A.F.T. Yokochi, R.L. Ely, Colloids. Surf. B-Biointerfaces 102, 611 (2013)M. Kanungo, M.M. Collinson, Langmuir 21, 827 (2005)J. Kukulka-Walkiewicz, M. Opallo, Solid State Ionics 157, 263 (2003)M. Opallo, J. Kukulka-Walkiewicz, Electrochim. Acta 46, 4235 (2001)A. Walcarius, V. Ganesant, Langmuir 22, 469 (2006)A.R. Howells, P.J. Zambrano, M.M. Collinson, Anal. Chem. 72, 5265 (2000)W.M. Aylward, P.G. Pickup, Electrochim. Acta 53, 3897 (2008

Reversible Electrochemical Ion Intercalation at an Electrified Liquid|liquid Interface Functionalised with Porphyrin Nanostructures

Ion intercalation into solid matrices influences the performance of key components in most energy storage devices (Li-ion batteries, supercapacitors, fuel cells, etc.). Electrochemical methods provide key information on the thermodynamics and kinetics of these ion transfer processes but are restricted to matrices supported on electronically conductive substrates. In this article, the electrified liquid|liquid interface is introduced as an ideal platform to probe the thermodynamics and kinetics of reversible ion intercalation with non-electronically active matrices. Zinc(II) meso-tetrakis(4-carboxyphenyl)porphyrins were self-assembled into floating films of ordered nanostructures at the water|a,a,a-trifluorotoluene interface. Electrochemically polarising the aqueous phase negatively with respect to the organic phase lead to organic ammonium cations intercalating into the zinc porphyrin nanostructures by binding to anionic carboxyl sites and displacing protons through ion exchange at neutral carboxyl sites. The cyclic voltammograms suggested a positive cooperativity mechanism for ion intercalation linked with structural rearrangements of the porphyrins within the nanostructures, and were modelled using a Frumkin isotherm. The model also provided a robust understanding of the dependence of the voltammetry on the pH and organic electrolyte concentration. Kinetic analysis was performed using potential step chronoamperometry, with the current transients composed of “adsorption” and nucleation components. The latter were associated with domains within the nanostructures where, due to structural rearrangments, ion binding and exchange took place faster. This work opens opportunities to study the thermodynamics and kinetics of purely ionic ion intercalation reactions (not induced by redox reactions) in floating solid matrices using any desired electrochemical method.</p

Mechanistic insights into the potentiodynamic electrosynthesis of PEDOT thin films at a polarizable liquid|liquid interface

Conducting polymer (CP) thin films find widespread use, for example in bioelectronic, energy harvesting and storage, and drug delivery technology. Electrosyn-thesis at a polarizable liquid|liquid interface using an aqueous oxidant and organic soluble monomer provides a route to free-standing and scalable CP thin films, such as poly(3,4- ethylenedioxythiophene) (PEDOT), in a single step at ambient conditions. Here, using the potentiodynamic technique of cyclic voltammetry, interfacial electrosynthesis involving ion exchange, electron transfer, and proton adsorption charge transfer processes is shown to be mechanistically distinct from CP electropolymerization at a solid electrode|electrolyte interface. During interfacial electrosynthesis, the applied interfacial Galvani potential difference controls the interfacial concentration of the oxidant, but not the CP redox state. Nevertheless, typical CP electropolymerization electrochemical behaviors, such as steady charge accumulation with each successive cycle and the appearance of a nucleation loop, were observed. By combining (spectro)electrochemical measurements and theoretical models, this work identifies the underlying mechanistic origin of each feature on the cyclic voltammograms (CVs) due to charge accumulated from Faradaic and capacitive processes as the PEDOT thin film grows. To prevent overoxidation during interfacial electrosynthesis with a powerful cerium aqueous oxidant, scan rates in excess 25 mV·s −1 were optimal. The experimental methodology and theoretical models outlined in this article provide a broadly generic framework to understand evolving CVs during interfacial electrosynthesis using any suitable oxidant/monomer combination</p