Organic bioelectronics: A new era for organic electronics

Background

This issue of “Biochimica et Biophysica Acta — General Subjects” is dedicated to organic bioelectronics, an interdisciplinary field that has been growing at a fast pace. Bioelectronics creates tremendous promise, excitement, and hype. The application of organic electronic materials in bioelectronics offers many opportunities and is fuelled by some unique features of these materials, such as the ability to transport ions.

Scope of review

This is a perspective on the history and current status of the field.

Major conclusions

Organic bioelectronics currently encompasses many different applications, including neural interfaces, tissue engineering, drug delivery, and biosensors. The interdisciplinary nature of the field necessitates collaborations across traditional scientific boundaries.

General significance

Organic bioelectronics is a young and exciting interdisciplinary field. This article is part of a Special Issue entitled Organic Bioelectronics — Novel Applications in Biomedicine.     

Electrically tunable organic bioelectronics for spatial and temporal manipulation of neuron-like pheochromocytoma (PC-12) cells

Background

Organic bioelectronic devices consisting of alternating poly(3,4-ethylenedioxythiophene) (PEDOT) and reduced graphite oxide (rGO) striped microelectrode arrays were fabricated by lithography technology. It has been demonstrated that the organic bioelectronic devices can be used to spatially and temporally manipulate the location and proliferation of the neuron-like pheochromocytoma cells (PC-12 cells).

Methods

By coating an electrically labile contact repulsion layer of poly(l-lysine-graft-ethylene glycol) (PLL-g-PEG) on the PEDOT electrode, the location and polarity of the PC-12 cells were confined to the rGO electrodes.

Results

The outgrowth of spatially confined bipolar neurites was found to align along the direction of the 20 μm wide electrode. The location of the PC-12 cells can also be manipulated temporally by applying electrical stimulation during the neurite differentiation of PC-12 cells, allowing the PC-12 cells to cross over the boundary between the PEDOT and the rGO regions and construct neurite networks in an unconfined manner where the contact repulsive coating of PLL-g-PEG was removed.

Conclusions

This adsorption and desorption of the PLL-g-PEG without and with electrical stimulation can be attributed to the tunable surface properties of the PEDOT microelectrodes, whose surface charge can switch from being negative to positive under electrical stimulation.

General significance

The electrically tunable organic bioelectronics reported here could potentially be applied to tissue engineering related to the development and regeneration of mammalian nervous systems. The spatial and temporal control in this device would also be used to study the synapse junctions of neuron–neuron contacts in both time and space domains. This article is part of a Special Issue entitled Organic Bioelectronics — Novel Applications in Biomedicine.     

Random CNT network and regioregular poly(3-hexylthiophen) FETs for pH sensing applications: A comparison

Background

Nowadays, there is a tremendous need for cheap disposable sensing devices for medical applications. Materials such as Carbon Nanotubes (CNTs) and regioregular P3HT are proven to offer a huge potential as cost-effective and solution processable semiconductors for (bio)sensing applications.

Methods

CNT-based field-effect transistors (CNT-FETs) as well as regioregular P3HT-based ones (P3HT-FETs) are fabricated and operated in the so-called electrolyte-gated configuration. The active layer of the P3HT-FETs consists of a spin-coated regioregular P3HT layer, which serves on one hand as the active sensing element and on the other hand as passivation layer for the transistor's metal contacts. The active layer of the nanotube transistors consists of a randomly distributed single walled CNT-network (> 90% semiconducting tubes) deposited from a CNT-ink solution by spin-coating.

Results

We compare both devices concerning their stability in aqueous environment and their response when exposed to buffers with different pH. We found that even if P3HT shows lower stability its pH sensitivity is reproducible even after long-term measurements.

Conclusion

CNT-FETs and P3HT-FETs offer different advantages and drawbacks concerning their stability in solution and the ease of fabrication. A discussion of their different sensing mechanisms as well as sensitivity is given here.

General Significance

This work reports on fast and cost-effective production of solution processable thin-film transistors based on carbon nanotubes and regioregular P3HT and demonstrates their suitability as reliable pH sensors. This article is part of a Special Issue entitled Organic Bioelectronics — Novel Applications in Biomedicine.     

Effect of Microorganisms and Microbial Metabolites on Apatite Dissolution

The dissolution rate of apatite was determined in batch reactors in organic acid solutions and in microbial cultures. Inoculum for the cultures was from biotite plus apatite crystals from a granite weathering profile in South Eastern Australia. In both the biotic and the abiotic experiments, etching of the apatite surface leads to the formation of elongated spires parallel to the c axis. Apatite dissolution rates in the inorganic, acetate, and oxalate solutions increase as pH decreases from approximately 10 -11 mol/m -2 · s -1 at initial pH 5.5 to 10 -7 mol/m -2 · s -1 at initial pH 2. Under mildly acidic to near neutral pH conditions, both oxalate and acetate increased apatite dissolution by up to an order of magnitude compared to the inorganic conditions. Acetate catalyzed the reaction by forming complexes with Ca, either in solution or at the mineral surfaces. Oxalate forms complexes with Ca as well, and can also affect reaction rates and stoichiometry by forming Ca-oxalate precipitates, thus affecting solution saturation states. In all abiotic experiments, net phosphate release to solution approaches zero even when solutions are apparently undersaturated by several orders of magnitude with respect to the solubility of an ideal fluoroapatite mineral. In the microbial experiments, two enrichment cultures increased both apatite and biotite dissolution by producing organic acids, primarily pyruvate, fermentation products, and oxalate, and by lowering bulk solution pH to between 3 and 5. However, the microorganisms were also able to increase phosphate release from apatite (by two orders of magnitude) without lowering bulk solution pH by producing pyruvate and other compounds.     

Hydralazine and Organic Nitrates Restore Impaired Excitation-Contraction Coupling by Reducing Calcium Leak Associated with Nitroso-Redox Imbalance

Although the combined use of hydralazine and isosorbide dinitrate confers important clinical benefits in patients with heart failure, the underlying mechanism of action is still controversial. We used two models of nitroso-redox imbalance, neuronal NO synthase-deficient (NOS1^−/−) mice and spontaneously hypertensive heart failure rats, to test the hypothesis that hydralazine (HYD) alone or in combination with nitroglycerin (NTG) or isosorbide dinitrate restores Ca²⁺ cycling and contractile performance and controls superoxide production in isolated cardiomyocytes. The response to increased pacing frequency was depressed in NOS1^−/− compared with wild type myocytes. Both sarcomere length shortening and intracellular Ca²⁺ transient (Δ[Ca²⁺]_i) responses in NOS1^−/− cardiomyocytes were augmented by HYD in a dose-dependent manner. NTG alone did not affect myocyte shortening but reduced Δ[Ca²⁺]_i across the range of pacing frequencies and increased myofilament Ca²⁺ sensitivity thereby enhancing contractile efficiency. Similar results were seen in failing myocytes from the heart failure rat model. HYD alone or in combination with NTG reduced sarcoplasmic reticulum (SR) leak, improved SR Ca²⁺ reuptake, and restored SR Ca²⁺ content. HYD and NTG at low concentrations (1 μm), scavenged superoxide in isolated cardiomyocytes, whereas in cardiac homogenates, NTG inhibited xanthine oxidoreductase activity and scavenged NADPH oxidase-dependent superoxide more efficiently than HYD. Together, these results revealed that by reducing SR Ca²⁺ leak, HYD improves Ca²⁺ cycling and contractility impaired by nitroso-redox imbalance, and NTG enhanced contractile efficiency, restoring cardiac excitation-contraction coupling.     

Analogs of iso-azepinomycin as potential transition-state analog inhibitors of guanase: Synthesis,biochemical screening,and structure–activity correlations of various selectively substituted imidazo[4,5-e][1,4]diazepines

Guanase is an important enzyme of the purine salvage pathway of nucleic acid metabolism and its inhibition has beneficial implications in viral, bacterial, and cancer therapy. The work described herein is based on a hypothesis that azepinomycin, a heterocyclic natural product and a purported transition state analog inhibitor of guanase, does not represent the true transition state of the enzyme-catalyzed reaction as closely as does iso-azepinomycin, wherein the 6-hydroxy group of azepinomycin has been translocated to the 5-position. Based on this hypothesis, and assuming that iso-azepinomycin would bind to guanase at the same active site as azepinomycin, several analogs of iso-azepinomycin were designed and successfully synthesized in order to gain a preliminary understanding of the hydrophobic and hydrophilic sites surrounding the guanase binding site of the ligand. Specifically, the analogs were designed to explore the hydrophobic pockets, if any, in the vicinity of N1, N3, and N4 nitrogen atoms as well as O⁵ oxygen atom of iso-azepinomycin. Biochemical inhibition studies of these analogs were performed using a mammalian guanase. Our results indicate that (1) increasing the hydrophobicity near O⁵ results in a negative effect, (2) translocating the hydrophobicity from N3 to N1 also results in decreased inhibition, (3) increasing the hydrophobicity near N3 or N4 produces significant enhancement of inhibition, (4) increasing the hydrophobicity at either N3 or N4 with a simultaneous increase in hydrophobicity at O⁵ considerably diminishes any gain in inhibition made by solely enhancing hydrophobicity at N3 or N4, and (5) finally, increasing the hydrophilic character near N3 has also a deleterious effect on inhibition. The most potent compound in the series has a K_i value of 8.0 ± 1.5 μM against rabbit liver guanase.     

Effect of potassium diformate in combination with different amounts and sources of excessive dietary copper on production performance in weaning piglets

Three studies with each 96 weaning piglets were conducted to evaluate the combinatory effect of potassium diformate and high dietary doses of Cu on production performance. In Exp. 1, increasing dietary Cu (25, 75, 125, 175 ppm Cu) were tested at either no or 1.8% potassium diformate. In Exp. 2, rising dietary levels of potassium diformate (0%, 0.6%, 1.2% and 1.8%) were tested at either 25 or 175 ppm Cu. In Exp. 3, a basal dietary Cu content of 15 ppm was compared with dietary Cu levels of 95 or 175 ppm, each of them added as either Cu sulphate or Cu amino acid chelate or Cu formate. Rising dietary additions of potassium diformate and Cu improved weight gain, feed intake and feed conversion rate of piglets. The combination of potassium diformate and Cu failed to act additively at highest dose levels of the two supplements. Cu sulphate was efficient as growth stimulating additive in all 3 experiments, Cu formate failed to stimulate production performance, Cu chelate tended to depress production performance and to increase blood plasma Cu compared to equivalent amounts of Cu from Cu sulphate.     

Metagenomic insights into strategies of carbon conservation and unusual sulfur biogeochemistry in a hypersaline Antarctic lake

Organic Lake is a shallow, marine-derived hypersaline lake in the Vestfold Hills, Antarctica that has the highest reported concentration of dimethylsulfide (DMS) in a natural body of water. To determine the composition and functional potential of the microbial community and learn about the unusual sulfur chemistry in Organic Lake, shotgun metagenomics was performed on size-fractionated samples collected along a depth profile. Eucaryal phytoflagellates were the main photosynthetic organisms. Bacteria were dominated by the globally distributed heterotrophic taxa Marinobacter, Roseovarius and Psychroflexus. The dominance of heterotrophic degradation, coupled with low fixation potential, indicates possible net carbon loss. However, abundant marker genes for aerobic anoxygenic phototrophy, sulfur oxidation, rhodopsins and CO oxidation were also linked to the dominant heterotrophic bacteria, and indicate the use of photo- and lithoheterotrophy as mechanisms for conserving organic carbon. Similarly, a high genetic potential for the recycling of nitrogen compounds likely functions to retain fixed nitrogen in the lake. Dimethylsulfoniopropionate (DMSP) lyase genes were abundant, indicating that DMSP is a significant carbon and energy source. Unlike marine environments, DMSP demethylases were less abundant, indicating that DMSP cleavage is the likely source of high DMS concentration. DMSP cleavage, carbon mixotrophy (photoheterotrophy and lithoheterotrophy) and nitrogen remineralization by dominant Organic Lake bacteria are potentially important adaptations to nutrient constraints. In particular, carbon mixotrophy relieves the extent of carbon oxidation for energy production, allowing more carbon to be used for biosynthetic processes. The study sheds light on how the microbial community has adapted to this unique Antarctic lake environment.     

The sensitivity of water chemistry to climate in a forested,nitrogen-saturated catchment recovering from acidification

Fluxes of major ions and nutrients were measured in the N-saturated mountain forest catchment-lake system of Čertovo Lake (Czech Republic) from 1998 to 2014. The lake has been rapidly recovering from atmospheric acidification due to a 90% decrease in sulphate (SO₄²⁻) deposition since the late 1980s and nitrate (NO₃⁻) contribution to the pool of strong acid anion and leaching of dissolved organic carbon (DOC) have increased. Present concentrations of base cations, phosphorus (P), total organic N (TON), and ionic (Al_i) and organically bound (Al_o) aluminium in tributaries are thus predominantly governed by NO₃⁻ and DOC leaching. Despite a continuing recovery lasting 25 years, the Čertovo catchment is still a net source of protons (H⁺), producing 44 mmol m⁻² yr⁻¹ H⁺ on a catchment-area basis (corresponding to 35 μmol L⁻¹ on a concentration basis). Retention of the deposited inorganic N in the catchment averages 20%, and ammonium consumption (51 mmol m⁻² yr⁻¹) and net NO₃⁻ production (28 mol m⁻² yr⁻¹) are together the dominant terrestrial H⁺ generating processes. In contrast, the importance of SO₄²⁻ release from the soils on terrestrial H⁺ production is continuously decreasing, with an average of 47 mmol m⁻² yr⁻¹ during the study. The in-lake biogeochemical processes reduce the incoming acidity by ∼40%, neutralizing 23 μmol L⁻¹ H⁺ (i.e., 225 mmol m⁻² yr⁻¹ on a lake-area basis). Denitrification and photochemical and microbial decomposition of DOC are the most important in-lake H⁺ consuming processes (50 and 39%, respectively), while hydrolysis of Al_i (from tributaries and photochemically liberated from Al_o) is the dominant in-lake H⁺ generating process. Because the trends in water chemistry and H⁺ balance in the catchment-lake system are increasingly related to variability in NO₃⁻ and DOC leaching, they have become sensitive to climate-related factors (drought, elevated runoff) and forest damage that significantly modify the leaching of these anions. During the study period, increased exports of NO₃⁻ (accompanied by Al_i and base cations) from the Čertovo catchment occurred after a dry and hot summer, after forest damage, and during elevated winter runoff. Increasing DOC export due to decreasing acid deposition was further elevated during years with higher runoff (and especially during events with lateral flow), and was accompanied by P, TON, and Al_o leaching. The climate-related processes, which originally “only” confounded chemical trends in waters recovering from acidification, may soon become the dominant variables controlling water composition in N-saturated catchments.     

Synthesis,anticancer activity,and SAR analyses of compounds containing the 5:7-fused 4,6,8-triaminoimidazo[4,5-e][1,3]diazepine ring system

Described herein are our limited structure–activity relationship (SAR) studies on a 5:7-fused heterocycle (1), containing the 4,6,8-triaminoimidazo[4,5-e][1,3]diazepine ring system, whose synthesis and potent broad-spectrum anticancer activity we reported a few years ago. Our SAR efforts in this study are mainly focused on judicial attachment of substituents at N-1 and N⁶-positions of the heterocyclic ring. Our results suggest that there is some subtle correlation between the substituents attached at the N-1 position and those attached at the N⁶-position of the heterocycle. It is likely that there is a common hydrophobic binding pocket on the target protein that is occupied by the substituents attached at the N-1 and N⁶-positions of the heterocyclic ligand. This pocket appears to be large enough to hold either a C-18 alkyl chain of N⁶ and no attachment at N-1, or a combined C-10 at N⁶ and a CH₂Ph at N-1. Any alkyl chain shorter or longer than C-10 at N⁶ with a CH₂Ph attached at N-1, would result in decrease of biological activity.