ELECTROKINETIC EFFECTS: CARBONIC ANHYDRASE AND CO2 ELECTRODE DYNAMICS

It is well known that the dynamic response rate of the Severinghaus-type CO₂ electrode is improved significantly in some cases by addition of the enzyme carbonic anhydrase to the electrode assembly. Hysteresis in the response rate also is reduced. Experimental data and modelling results indicate that catalysis of the CO₂ hydration reaction in the bulk of the bicarbonate layer (the Nernst film) is not responsible for the improved response behavior, Evidence is presented to show that catalysis in the electrostatic double layer region at the glass electrode surface is a possible explanation. This proposed phenomenon may have widespread implications for the optimal design of analytical devices, commercial processes involving electrochemical phenomena, and may also provide insight into electrobiologi-cal processes.     

Design and synthesis of a novel class of carbonic anhydrase-IX inhibitor 1-(3-(phenyl/4-fluorophenyl)-7-imino-3H-[1,2,3]triazolo[4,5d]pyrimidin 6(7H)yl)urea

Carbonic anhydrase IX (CAIX) is a promising target in cancer therapy especially in the case of hypoxia-induced tumors. The selective inhibition of CA isozymes is a challenging task in drug design and discovery process. Here, we performed fluorescence-binding studies and inhibition assay combined with molecular docking and molecular dynamics (MD) simulation analyses to determine the binding affinity of two synthesized triazolo-pyrimidine urea derived (TPUI and TPUII) compounds with CAIX and CAII. Fluorescence binding results are showing that molecule TPUI has an excellent binding-affinity for CAIX (k_D = 0.048 μM). The TPUII also exhibits an appreciable binding affinity (k_D = 7.52 μM) for CAIX. TPUI selectively inhibits CAIX as compared to TPUII in the 4-NPA assay. Docking studies show that TPUI is spatially well-fitted in the active site cavity of CAIX, and is involve in H-bond interactions with His94, His96, His119, Thr199 and Thr200. MD simulation studies revealed that TPUI efficiently binds to CAIX and essential active site residual interaction is consistent during the entire simulation of 40 ns. These studies suggest that TPUI appeared as novel class of CAIX inhibitor, and may be used as a lead molecule for the development of potent and selective CAIX inhibitor for the hypoxia-induced cancer therapy.     

Colour features and pigment composition of Italian carbonic macerated red wines

Thirty commercially available Italian carbonic macerated young red wines, have been analysed by HPLC–DAD–MS with the aim to characterise their pigment composition and find possible correlations with the colour features evaluated by means of spectrophotometric measurements. The composition in anthocyanin monoglucosides, acetates, p-coumarates as well as that in pyranoanthocyanins and direct and ethyl-bridged adducts with flavanols, was studied. Because of the peculiar maceration process, carbonic macerated wines demonstrated to be qualitatively rich in pyranoanthocyanins and pigment adducts. A number of ethyl-bridged anthocyanin isomers was found, together with significant contents of vitisin A and vitisin B (up to 15.5 mg/L as a sum). Malvidin-3-glc-4-vinylphenol was the main pyranoanthocyanin-vinylphenol adduct (up to 1.10 mg/L). The colour features of the wines were broadly distributed as a consequence of the percentage of carbonic macerated wine present in the marketed product. The statistical treatment of the entire data set revealed that pyranoanthocyanins are positively correlated with colour density (while no correlation was found for monoglucosides) and that direct adducts and/or ethyl-bridged compounds can play a role for what concerns the hue of carbonic macerated wines.     

Preparation and evaluation of in situ gelling ophthalmic drug delivery system for methazolamide

Purpose: In this study, a thermosensitive in situ gelling vehicle was prepared to increase the precorneal resident time and the bioavailability of methazolamide (MTA). Method: Poloxamer analogs were used as the gelling agents, and the in situ gel was obtained by using a cold method. The gelation temperature, rheological properties, in vitro release as well as in vivo evaluation (the elimination of MTA in aqueous humor and intraocular-lowering effect) of the optimized formulations were investigated. Results: The optimum concentrations of poloxamer analogs for the in situ gel-forming delivery system were 21% (w/w) poloxamer 407 and 10% (w/w) poloxamer P188. This formulation was able to flow freely under nonphysiological conditions and underwent sol–gel transition in the cul-de-sac upon placement into the eye. In vitro release studies demonstrated a diffusion-controlled release of MTA from the poloxamer solutions over a period of 10 hours. In vivo evaluation indicated that the poloxamer solutions had a better ability to retain drug than MTA eyedrops did. Conclusion: These results suggested that in situ gelling ophthalmic drug delivery system may hold some promise in ocular MTA delivery.     

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沙坪场气田石炭系气藏是西南油气田分公司重庆气矿继五百梯、龙门石炭系气藏之后的又一重要发现 ,它是川气东输工程的骨干气田 ,探明储量近 4 0 0× 10 8m3 ,属大储量气田。据 2 0 0 1年 5月完成的开发方案 ,沙坪场石炭系气藏的生产规模为 13× 10 8m3 /a ,推荐的开发方案能否顺利实施 ,对整个东输工程和该气田的开发至关重要。然而 ,气藏局部出现的边水活跃现象不容忽视 ,在试采期间 ,天东 90井投产仅 17d就开始产地层水 ,且水量迅速增至 98.76m3 /d ,该井见水突然、产水量大 ,在川东石炭系气藏中实属罕见。文章通过剖析沙坪场气田石炭系气藏出水特征 ,结合气藏动、静态研究 ,再借鉴川东其它有水气藏的分析研究成果 ,认为沙坪场石炭系气藏天东 90井出现的早期出水属边水沿裂缝水窜 ,天东 90井附近产层存在大、中裂缝 ,水侵方向来自东翼的沙③号断层 ,但边水能量有限。     

Ammonia production using iron nitride and water as hydrogen source under mild temperature and pressure

Ammonia generation was studied in the reaction between water and nitrogen-containing iron at 323 K and atmospheric pressure. Similar to metallic Fe, the interstitial compound Fe₃N reduced water through Fe oxidation to produce hydrogen gas, while the N combined with atomic hydrogen to produce ammonia as a byproduct. The addition of carbon dioxide to this system accelerated the reaction with concomitant consumption of carbon dioxide. The promoted ammonia production upon addition of carbon dioxide can be attributed to the generation of atomic hydrogen from the redox reaction of carbonic acid and Fe, as well as removal of used Fe from the reaction system through the formation of a soluble carbonato complex. When carbonate was added to the reaction system, the production rates of ammonia and hydrogen increased further. The results here confirmed that ammonia can be synthesized from iron nitride under mild conditions by utilizing carbon dioxide.     

Enzyme-Containing Paints Inhibit the Growth of Marine Microorganisms

A new strategy to prevent the biofouling of water-submerged surfaces is presented here. In particular, the authors showthat carbonic anydrase from Methanosarcina thermophila can be entrapped into polyacrylic paints, preserving enzyme activity. In addition, the authors also show that enzyme-containing paints inhibit the growth of marine microorganims, preventing biofouling.     

A Series of Thiadiazolyl-Benzenesulfonamides Incorporating an Aromatic Tail as Isoform-Selective,Potent Carbonic Anhydrase II/XII Inhibitors

We describe the synthesis of a series of thiadiazolyl-benzenesulfonamide derivatives carrying an aromatic tail linked by an amide linker ( 12–34 ), as human carbonic anhydrase (hCA) inhibitors. These thiadiazol derivatives were evaluated against four physiologically relevant CA isoforms (hCA I, II, IX, and XII), and demonstrated intriguing inhibitory activity against CA II with K_i values in the range of 2.4–31.6 nM. Besides hCA II, also hCA XII activity was potently inhibited by some of the derivatives (K_i=1.5–88.5 nM), producing dual inhibitors of both isoforms. Notably, compound 17 was the most potent dual CA II (K_i=3.1 nM) and XII (K_i=1.5 nM) inhibitor with a significant selectivity ratio over CA I and IX isoforms. In conclusion, although all compounds exhibited preferential activity towards hCA II, the nature of the substituents at the tail part of the main scaffold influenced the activity and selectivity toward other isoforms.