Novel, Stable Catholyte for Aqueous Organic Redox Flow Batteries: Symmetric Cell Study of Hydroquinones with High Accessible Capacity.

Owing to their broad range of redox potential, quinones/hydroquinones can be utilized for energy storage in redox flow batteries. In terms of stability, organic catholytes are more challenging than anolytes. The two-electron transfer feature adds value when building all-quinone flow battery systems. However, the dimerization of quinones/hydroquinones usually makes it difficult to achieve a full two-electron transfer in practical redox flow battery applications. In this work, we designed and synthesized four new hydroquinone derivatives bearing morpholinomethylene and/or methyl groups in different positions on the benzene ring to probe molecular stability upon battery cycling. The redox potential of the four molecules were investigated, followed by long-term stability tests using different supporting electrolytes and cell cycling methods in a symmetric flow cell. The derivative with two unoccupied ortho positions was found highly unstable, the cell of which exhibited a capacity decay rate of ~50% per day. Fully substituted hydroquinones turned out to be more stable. In particular, 2,6-dimethyl-3,5-bis(morpholinomethylene)benzene-1,4-diol (asym-O-5) displayed a capacity decay of only 0.45%/day with four-week potentiostatic cycling at 0.1 M in 1 M H3PO4. In addition, the three fully substituted hydroquinones displayed good accessible capacity of over 82%, much higher than those of conventional quinone derivatives.

Aqueous Solubility of Organic Compounds for Flow Battery Applications: Symmetry and Counter Ion Design to Avoid Low-Solubility Polymorphs.

Flow batteries can play an important role as energy storage media in future electricity grids. Organic compounds, based on abundant elements, are appealing alternatives as redox couples for redox flow batteries. The straightforward scalability, the independence of material sources, and the potentially attractive price motivate researchers to investigate this technological area. Four different benzyl-morpholino hydroquinone derivatives were synthesized as potential redox active species. Compounds bearing central symmetry were shown to be about an order of magnitude less soluble in water than isomers without central symmetry. Counter ions also affected solubility. Perchlorate, chlorate, sulfate and phosphate anions were investigated as counter ions. The formations of different polymorphs was observed, showing that their solubility is not a function of their structure. The kinetics of the transformation can give misleading solubility values according to Ostwald's rule. The unpredictability of both the kinetics and the thermodynamics of the formation of polymorphs is a danger for new organic compounds designed for flow battery applications.

Organic Redox Species in Aqueous Flow Batteries: Redox Potentials, Chemical Stability and Solubility.

Organic molecules are currently investigated as redox species for aqueous low-cost redox flow batteries (RFBs). The envisioned features of using organic redox species are low cost and increased flexibility with respect to tailoring redox potential and solubility from molecular engineering of side groups on the organic redox-active species. In this paper 33, mainly quinone-based, compounds are studied experimentially in terms of pH dependent redox potential, solubility and stability, combined with single cell battery RFB tests on selected redox pairs. Data shows that both the solubility and redox potential are determined by the position of the side groups and only to a small extent by the number of side groups. Additionally, the chemical stability and possible degradation mechanisms leading to capacity loss over time are discussed. The main challenge for the development of all-organic RFBs is to identify a redox pair for the positive side with sufficiently high stability and redox potential that enables battery cell potentials above 1 V.

Drugs against Mycobacterium tuberculosis 3-isopropylmalate dehydrogenase can be developed using homologous enzymes as surrogate targets.

3-Isopropylmalate dehydrogenase (IPMDH) from Mycobacterium tuberculosis (Mtb) may be a target for specific drugs against this pathogenic bacterium. We have expressed and purified Mtb IPMDH and determined its physicalchemical and enzymological properties. Size-exclusion chromatography and dynamic light scattering measurements (DLS) suggest a tetrameric structure for Mtb IPMDH, in contrast to the dimeric structure of most IPMDHs. The kinetic properties (kcat and Km values) of Mtb IPMDH and the pH-dependence of kcat are very similar to both Escherichia coli (Ec) and Thermus thermophilus (Tt) IPMDHs. The stability of Mtb IPMDH in 8 M urea is close to that of the mesophilic counterpart, Ec IPMDH, both of them being much less stable than the thermophilic (Tt) enzyme. Two known IPMDH inhibitors, O-methyl oxalohydroxamate and 3-methylmercaptomalate, have been synthesised. Their inhibitory effects were found to be independent of the origin of IPMDHs. Thus, experiments with either Ec or Tt IPMDH would be equally relevant for designing specific inhibitory drugs against Mtb IPMDH.

Middle ear gas pressure regulation: the relevance of mastoid obliteration.

OBJECTIVES: To establish a mathematical model of middle ear gas pressure regulation and to discuss potential implications for pathophysiology-oriented theoretical approach to middle ear surgery, with particular attention to mastoid obliteration. BACKGROUND: Numerous studies support that small mastoid volume is associated with cholesteatoma. Latest studies show that mastoid obliteration is an effective technique to lower the recurrence rate in these ears. METHODS: A mathematical model was used to predict the development of gas pressure balance in the function of different middle ear volumes (VME), considering normal and dysfunctional Eustachian tube. Published data as gas pressure input values and our 3D CT reconstruction data in healthy and pathologic middle ears of children were applied. RESULTS: The model predicted ≤6.66 daPa pressure fluctuations in VME ≥3 ml, compared to ≥16 daPa of a VME ≤1 ml at perfect ET function, because of the different pressure change rate and pressure buffer effect of the MEs. Substantially larger fluctuations can be expected in a VME <3 ml with malfunctioning ET. Modeling mastoid obliteration predicts similar pressure fluctuations to a VME ≥3 ml resulting from elimination of gas exchange surface. CONCLUSION: Pressure change is faster in smaller MEs than in larger ones. Healthy MEs between 3 and 6 ml are very sensitive to the duration of a potential ET dysfunction to develop ME pathology. In MEs with poor mastoid pneumatization and dysfunctional ET, typical in cholesteatoma cases, mastoid obliteration as surgical reduction of mucosal surface for gas exchange can improve ME gas pressure balance resulting in better long-term outcome.

Matrix metalloproteinase inhibitors: a critical appraisal of design principles and proposed therapeutic utility.

Matrix metalloproteinases (MMPs) play an important role in tissue remodelling associated with various physiological and pathological processes, such as morphogenesis, angiogenesis, tissue repair, arthritis, chronic heart failure, chronic obstructive pulmonary disease, chronic inflammation and cancer metastasis. As a result, MMPs are considered to be viable drug targets in the therapy of these diseases. Despite the high therapeutic potential of MMP inhibitors (MMPIs), all clinical trials have failed to date, except for doxycycline for periodontal disease. This can be attributed to (i) poor selectivity of the MMPIs, (ii) poor target validation for the targeted therapy and (iii) poorly defined predictive preclinical animal models for safety and efficacy. Lessons from previous failures, such as recent discoveries of oxidative/nitrosative activation and phosphorylation of MMPs, as well as novel non-matrix related intra- and extracellular targets of MMP, give new hope for MMPI development for both chronic and acute diseases. In this article we critically review the major structural determinants of the selectivity and the milestones of past design efforts of MMPIs where 2-/3-dimensional structure-based methods were intensively applied. We also analyse the in vitro screening and preclinical/clinical pharmacology approaches, with particular emphasis on drawing conclusions on how to overcome efficacy and safety problems through better target validation and design of preclinical studies.

Pd(I) phosphine carbonyl and hydride complexes implicated in the palladium-catalyzed oxo process.

Reduction of compound "Pd(bcope)(OTf)2" [bcope = (c-C8H14-1,5)PCH2CH2P(c-C8H14-1,5); OTf = O3SCF3] with H2/CO yields a mixture of Pd(I) compounds [Pd2(bcope)2(CO)2](OTf)2 (1) and [Pd2(bcope)2(mu-CO)(mu-H)](OTf) (2), whereas reduction with H2 or Ph3SiH in the absence of CO leads to [Pd3(bcope)3(mu3-H)2](OTf)2 (3). Exposure of 3 to CO leads to 1 and 2. The structures of 1 and 3 have been determined by X-ray diffraction. Complex [Pd2(bcope)2(CO)2](2+) displays a metal-metal bonded structure with a square planar environment for the Pd atoms and terminally bonded CO ligands and is fluxional in solution. DFT calculations aid the interpretation of this fluxional behavior as resulting from an intramolecular exchange of the two inequivalent P atom positions via a symmetric bis-CO-bridged intermediate. A cyclic voltammetric investigation reveals a very complex redox behavior for the "Pd(bcope)(OTf)2"/CO system and suggests possible pathways leading to the formation of the various observed products, as well as their relationship with the active species of the PdL2(2+)/CO/H2-catalyzed oxo processes (L2 = diphosphine ligands).

New electron-deficient chiral phosphines: (4R,5R)-1,3-bis(trifluoromethanesulfonyl)perhydro-1,3,2-benzodiazaphosphol-2-yl] substituted amines.

Three chiral electron-deficient phosphine ligands, [(4R,15R)-,3-bis(trifluoromethanesulfonyl)perhydro-1,3,2-benzodiazaphosphol-2-yl]diethylamine, C(12)H(20)F(6)N(3)O(4)PS(2), (IIIa), [(4R,5R)-1,3-bis(trifluoromethanesulfonyl)perhydro-1,3,2-benzodiazaphosphol-2-yl]dimethylamine, C(10)H(16)F(6)N(3)O(4)PS(2), (IIIb), and bis[(4R,5R)-1,3-bis(trifluoromethanesulfonyl)perhydro-1,3,2-benzodiazaphosphol-2-yl]methylamine, (IV), as the chloroform solvate, C(17)H(23)F(12)N(5)O(8)P(2)S(4).0.98CHCl(3), have been prepared from (1R,2R)-N,N'-bis(trifluoromethanesulfonyl)-1,2-cyclohexanediamine and diethyl phosphoramidous dichloride, dimethyl phosphoramidous dichloride or methyl imidodiphosphorus tetrachloride. The pi-acceptor abilities of these new types of ligands have been evaluated by X-ray determination of the P-N bond lengths; it has been found that the most promising ligand is the bis(phosphine) (IV).