Platinum metallodrug-protein binding studies by capillary electrophoresis-inductively coupled plasma-mass spectrometry: characterization of interactions between Pt(II) complexes and human serum albumin

Characterizing how platinum metallocomplexes bind to human serum albumin (HSA) is essential in evaluating anticancer drug candidates. Using cisplatin as a reference complex, the application of capillary electrophoresis (CE) to reliably assess drug/HSA interactions was validated. Since this complex is small compared to the size of the protein, the binding response could only be recognized when applying CE coupled to a (platinum) metal-specific mode of detection, namely inductively coupled plasma-mass spectrometry (ICP-MS). This coupling allowed for confirmation of a specific affinity of cisplatin and novel Pt complexes to HSA, measurement of the kinetics of binding reactions, and determination of the number of drug molecules attached to the protein. As the cisplatin/HSA molar ratio increased, the reaction rate became faster with a maximum on the kinetic curve appearing at about 50 h of incubation at 20 times excess of cisplatin. The reaction was characterized as a pseudo-first order reaction with the rate constant k = 0.003 min(-1) at 37 degrees C. When incubated with a 20-fold excess of cisplatin, HSA bound up to 10 mol of Pt per mol of the protein. This is indicative for a strong metal-protein coordination occurring at several HSA sites other than the only protein cysteine residue. Structural analogs of cisplatin, bearing aminoalcohol ligands, showed comparable protein binding reactivity and stoichiometry but a common equilibrium was not reached even after one week of incubation. Also apparent was a two-step mechanism of the binding reaction. Results demonstrated the suitability of CE-ICP-MS as a rapid assay for high-throughput studying of drug/HSA interactions.     

Tunable negative index metamaterial employing in-plane switching mode at terahertz frequencies

We analysed the response of a tunable liquid crystal metamaterial transducer in the terahertz frequency range. Tunability of scattering parameters is achieving by an in-plane switching (IPS) effect. The metamaterial structure is based on Ω-shape resonators. A full-wave analysis technique based on the finite-difference time-domain (FDTD) method was performed using the QuickWave 3D electromagnetic solver. Terahertz transmission properties of the metamaterial structure can be controlled by the director of the liquid crystal layer. The effective refractive index for operation frequency varies from negative to positive values. A novel approach to switching of metamaterial transducer by IPS mode is presented.     

Probability issues in molecular design: predictive and modeling ability in 3D-QSAR schemes

In the current work we investigated 3D-QSAR data by the use of the coupled leave-several-out (LSO) and leave-one-out (LOO) cross-validation (CV) procedures. We verified the above mentioned scheme using both simulated data and real 3D QSAR data describing a series of CoMFA steroids, heterocyclic azo dyes and styrylquinoline HIV integrase inhibitors. Unlike in standard analyses, this technique characterizes individual method not by a single performance metrics but screens a whole possible modeling space by sampling different molecules into the training and test sets, respectively. This allowed us for the discussion of the information included in the estimators validating cross-validation procedures, as well as the comparison of the efficiency of several 3D QSAR schemes, in particular, Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Surface Analysis (CoMSA). Moreover, it allows one to acquire some general knowledge about predictive and modeling ability in 3D QSAR method.     

Hydrophobic modification of nanocellulose and all-cellulose composite films using deep eutectic solvent as a reaction medium

Cellulose - In this work, deep eutectic solvent (DES) based on imidazole and triethylmethylammonium chloride was used as a reaction medium for the esterification of cellulose nanofiber (CNF) and...     

Kinetic study of the reaction of OH with CH2I2

Flash photolysis (FP) coupled to resonance fluorescence (RF) was used to measure the absolute rate coefficients (k(1)) for the reaction of OH(X(2)Π) radicals with diiodomethane (CH(2)I(2)) over the temperature range 295-374 K. The experiments involved time-resolved RF detection of the OH (A(2)Σ(+)→X(2)Π transition at λ = 308 nm) following FP of the H(2)O/CH(2)I(2)/He mixtures. The OH(X(2)Π) radicals were produced by FP of H(2)O in the vacuum-UV at wavelengths λ > 120 nm. Decays of OH radicals in the presence of CH(2)I(2) are observed to be exponential, and the decay rates are found to be linearly dependent on the CH(2)I(2) concentration. The results are described by the Arrhenius expression k(1)(T) = (4.2 ± 0.5) × 10(-11) exp[-(670 ± 20)K/T] cm(3) molecule(-1) s(-1). The implications of the reported kinetic results for understanding the atmospheric chemistry of CH(2)I(2) are discussed.     

Ru/CeO2催化剂催化苯乙烯氢甲氧基羰基化反应高选择性制备直链酯类化合物

酯类化合物在工业上具有广泛应用,例如可用于合成香水、调味剂(味精)、洗涤剂和表面活性剂等.其中,烯烃的氢烷氧基羰基化反应是一种合成酯类化合物的重要方法,其低消耗、100%的原子经济性和原料的易获得等优势使其在制备酯类化合物中成为一个有效且实际可行的方法.对于该反应,文献多采用Pd或Rh的络合均相催化剂,其中控制反应过程中直链酯类化合物(L)和支链酯类化合物(B)的选择性是一项颇具挑战性的课题.虽然目前可通过配体的设计和修饰来调节,但多集中在均相催化体系,因此在选择性调变方面的研究仍很欠缺.相对于均相催化,多相催化由于产物易分离和提纯、催化剂可循环使用等优势而逐渐引起了研究者的广泛关注.在多相催化体系中, Pd负载在强酸性树脂作为催化剂已被应用于苯乙烯氢甲氧基羰基化反应,但在该反应中支链酯类化合物为主要产物.因此,寻找一个可有效改善多相反应体系中选择性问题的方法是非常有意义的.在本研究工作中,我们分别以CeO2纳米颗粒(NP)、CeO2纳米棒(Rod)和CeO2纳米立方体为载体,利用浸渍法制备了Ru/CeO2、Ru/CeO2-rod和Ru/CeO2-cube三种催化剂,并进一步用于苯乙烯氢甲氧基羰基化反应.探究了CO压力、反应温度和反应时间对三种催化剂催化苯乙烯氢甲氧基羰基化反应的影响.结果表明, Ru/CeO2作为多相催化剂催化苯乙烯氢甲氧基羰基化反应时,苯乙烯选择性高于99%,直链酯选择性为83%,支链酯选择性为12%.机理研究表明,该反应为自由基机理.动力学分析表明,该反应的反应活化能为48.50 k Jmol^–1.结合三种催化剂的反应活性以及HRTEM结构表征结果可知,该反应中L/B比值与Ru的尺寸有较大关系.进一步的拉曼表征和NH3-TPD表征结果证明, Ru的尺寸与金属-载体之间的相互作用以及催化剂表面的氧空位浓度有直接关系.     

2,3‐Dihydro‐1,3‐benzothiazol‐2‐iminium monohydrogen sulfate and 2‐iminio‐2,3‐dihydro‐1,3‐benzothiazole‐6‐sulfonate: a combined structural and theoretical study

The 2‐aminobenzothiazole sulfonation intermediate 2,3‐dihydro‐1,3‐benzothiazol‐2‐iminium monohydrogen sulfate, C₇H₇N₂S⁺·HSO₄⁻, (I), and the final product 2‐iminio‐2,3‐dihydro‐1,3‐benzothiazole‐6‐sulfonate, C₇H₆N₂O₃S₂, (II), both have the endocyclic N atom protonated; compound (I) exists as an ion pair and (II) forms a zwitterion. Intermolecular N—H...O and O—H...O hydrogen bonds are seen in both structures, with bonding energy (calculated on the basis of density functional theory) ranging from 1.06 to 14.15 kcal mol⁻¹. Hydrogen bonding in (I) and (II) creates DDDD and C(8)C(9)C(9) first‐level graph sets, respectively. Face‐to‐face stacking interactions are observed in both (I) and (II), but they are extremely weak.     

Elimination of autofluorescence background from fluorescence tissue images by use of time-gated detection and the AzaDiOxaTriAngulenium (ADOTA) fluorophore

Sample autofluorescence (fluorescence of inherent components of tissue and fixative-induced fluorescence) is a significant problem in direct imaging of molecular processes in biological samples. A large variety of naturally occurring fluorescent components in tissue results in broad emission that overlaps the emission of typical fluorescent dyes used for tissue labeling. In addition, autofluorescence is characterized by complex fluorescence intensity decay composed of multiple components whose lifetimes range from sub-nanoseconds to a few nanoseconds. For these reasons, the real fluorescence signal of the probe is difficult to separate from the unwanted autofluorescence. Here we present a method for reducing the autofluorescence problem by utilizing an azadioxatriangulenium (ADOTA) dye with a fluorescence lifetime of approximately 15 ns, much longer than those of most of the components of autofluorescence. A probe with such a long lifetime enables us to use time-gated intensity imaging to separate the signal of the targeting dye from the autofluorescence. We have shown experimentally that by discarding photons detected within the first 20 ns of the excitation pulse, the signal-to-background ratio is improved fivefold. This time-gating eliminates over 96 % of autofluorescence. Analysis using a variable time-gate may enable quantitative determination of the bound probe without the contributions from the background.