Electronic structure of brain: structure-activity relationships between electronic structure and neurotransmitters based on molecular hardness concept

In order to understand the relation between the electronic structure of neurotransmitters and the brain, a model of the brain based on absolute hardness (eta) and absolute electronegativity (chi) is described. It was found that the coordinate r(chi, eta) of electronic structures of neurotransmitters obtained using the parameters eta and chi can be graphically classified into three groups: catecholamine type (group I), gamma-aminobutanoic acid (GABA) type (group II), and acetylcholine (ACh) type (group III) in the eta-chi diagram. The results suggest that the brainstem and neocortex in the brain are chemically soft and hard, respectively, because they show that the myelinated nerve is chemically soft and the unmyelinated nerve is chemically hard. If one calculates the r(chi, eta) to understand which group a drug belongs to, one can predict the target receptors of the drug from the eta-chi diagram. Using eta-chi maps, one is then able to design medications like antidepressants, tranquilizers, and ACh agonists.     

Prediction of endocrine disruptors based on a new structure-activity relationship for sex and environmental hormones using chemical hardness concept.

Classification of the relationship between electronic structures and biological activities of endocrine disruptors (so-called environmental hormones) was attempted using the parameters of absolute hardness (eta), absolute electronegativity (chi), and global softness (S), approximately defined as eta=1/2(epsilonLUMO-epsilonHOMO), chi=-1/2(epsilonHOMO+ epsilonLUMO), and S=1/eta, respectively, based on the hardness concept. The strength of binding affinity and toxicity of the chemicals were approximately proportional to the absolute hardness, and laterally toxic chlorinated PCDDs, PCBs, and DDTs are classified as chemically soft. Here we found that the electronic structures of environmental hormones can be classified into four main groups: 17beta-estradiol type (group I), testosterone type (group II), thyroxine type (group III), and HCH (hexachlorocyclohexane) type (group IV). Therefore, if we can predict the coordinate (chi, eta) of the electronic structure of one chemical on the eta-chi activity diagram, we would be able to predict the receptor with which the chemicals (environmental hormones) interact. For instance, 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) is classified in group II, therefore, it would bind with the thyroid receptor more than the estrogen receptor (group I). It appears that dibutyl phthalate would not interact with estrogen receptor because it does not belong to group I. In addition, the coordinates of these four groups do not complementarily overlap with the electronic structures of 20 natural amino acid residues. The eta-chi activity diagram is a new tool for the prediction of the toxicity and biological activity of environmental hormones.     

Development of soft-based double-stranded peptide chelators which selectively separate europium and lanthanum ions based on the hardness concept

New double-stranded peptide chelators (1) conjugated Cat (2,3-dihydroxybenzoic acid) were synthesized and formed a molecular complex 1-Eu(3+) (or 1-Lu(3+)) with Eu(3+) and Lu(3+) but not La(3+). The double-stranded peptide chelator may prove to be useful tools for studying the selective separation of lanthanide ions.     

A quantum theory of chemical processes and reaction rates based on diabatic electronic functions coupled in an external field

The method discussed in this work provides a theoretical framework where simple chemical reactions resemble any other standard quantum process, i.e., a transition in quantum state mediated by the electromagnetic field. In our approach, quantum states are represented as a superposition of electronic diabatic basis functions, whose amplitudes can be modulated by the field and by the external control of nuclear configurations. Using a one-dimensional three-state model system, we show how chemical structure and dynamics can be represented in terms of these control parameters, and propose an algorithm to compute the reaction probabilities. Our analysis of effective energy barriers generalizes previous ideas on structural similarity between reactant, and product, and transition states using the geometry of conventional reaction paths. In the present context, exceptions to empirical rules such as the Hammond postulate appear as effects induced by the environment that supplies the external field acting on the quantum system.     

Steric and electronic contributions to conformational effects on chemical shifts of acyclic alcohols

Our calculations on bi- and polycyclic alcohols reveal that the Mulliken charge distribution and chemical shift patterns due to hyperconjugation of lone pairs on oxygen with neighboring groups break down or are attenuated for certain spatial relationships of the hydroxyl group. Since in strained ring systems other effects on these parameters may be present, we applied a similar analysis to acyclic alcohols. Calculations at the B3LYP/6-31G^* level on conformers of methanol, ethanol, 1- and 2-propanol, 2-methyl-1-propanol, 2-methyl-2-propanol, 2-butanol, 2-methyl-2-butanol, 1- 2- and 3-pentanol and 2-methyl-3-pentanol, where hyperconjugation may be present, reveal steric effects as modifiers of hyperconjugative patterns affecting carbon-13 chemical shifts in such alcohols. Contrary to what is observed in bi- and policyclic systems, where electrostatic effects interfere with effects due to hyperconjugation, these steric effects may be the main cause for the attenuation of deshielding of nuclei that are subject to hyperconjugation. Electrostatic effects are also present but they do not interfere with hyperconjugation by lone pairs. Conformational effects fall off sharply after the third carbon in the chain.     

Peptide reagent design based on physical and chemical properties of amino acid residues

It has tremendous values for both drug discovery and basic research to develop a solid bioinformatical tool for guiding peptide reagent design. Based on the physical and chemical properties of amino acids, a new strategy for peptide reagent design, the so-called AABPD (amino acid based-peptide design), is proposed. The peptide samples in a training dataset are described by a series of HMLP (heuristic molecular lipophilicity potential) parameters and other physicochemical properties of amino acid residues that form a three-dimensional data matrix where each component is defined by three indexes: the first index refers to the peptide samples, the second to the amino acid positions, and the third to the amino acid parameters. The binding free energy between a peptide ligand and its protein receptor is calculated by a linear free energy equation through the physicochemical parameters, resulting in a set of simultaneous linear equations between the bioactivity of the peptides and the physicochemical properties of amino acids. An iterative double least square technique is developed for the solution of the three-dimensional simultaneous linear equation set to determine the amino acid position coefficients of peptide sequence and the physicochemical parameter coefficients of amino acid residues alternately. The two sets of coefficients thus obtained are used for predicting the bioactivity of other query peptide reagents. Two calculation examples, the peptide substrate specificity of the SARS coronavirus 3C-like proteinase and the affinity prediction for epitope-peptides with Class I MHC molecules are studied by using the peptide reagent design strategy.     

A synthesis of chalcones and their thiophene analogs based onβ-chlorovinylketones

A newly developed synthesis [1–3] of chalcones (arylstyryl ketones), based on condensing aryl--chlorovinylketones with ethers of mono- and dihydric phenols in the presence of stannic chloride, is extended. A number of chalcones not previously described are obtained in good yield and derivatives prepared. Hitherto undescribed nitroketones are obtained by addition of nitromethane and 2-nitropropane to an activated double bond of the chalcones and a thiophene analog of a chalcone.     

An immunoassay for bisphenol A based on direct hapten conjugation to the polystyrene surface of microtiter plates

Based on direct hapten coated format a competitive indirect enzyme-linked immunosorbent assay (ciELISA) for bisphenol A (BPA) was developed. Polystyrene surface was modified by 3-Aminopropyltriethoxysilane (APTES) to produce amino groups after H₂SO₄/HNO₃-pre-treatment. 4,4-bis (4-hydroxyphenyl) valeric acid (BVA) which is analogue of BPA, was successfully immobilized on the surface of microtiter plates by N,N′-dicyclohexylcarbodiimide (DCC) method. The essential steps of the assay were optimized, especially blocking procedure which is key step to prevent unspecific binding of antibody. The results indicated that compared with hapten-protein coated format (IC₅₀ = 176.67 ng ml⁻¹, LOD = 15.90 ng ml⁻¹), the direct hapten coated format (IC₅₀ = 23.50 ng ml⁻¹, LOD = 0.27 ng ml⁻¹) could improve assay sensitivity and the detection ranges were 2.30 ng∼157.60 ng ml⁻¹ with good signal reproducibility (P value > 0.05) after careful optimization of assay conditions. Tap water samples and seawater samples were spiked with a known amount of BPA and measured by ciELISA. The average recoveries were between 70 and 142%. As far as we are aware this is the most sensitive ELISA for BPA yet reported.     

An electrochemical sensor based on CuO nanoparticle for simultaneous determination of hydrazine and bisphenol A

In the present research, the direct electrochemical oxidation of hydrazine in the presence of bisphenol A was investigated at a copper oxide nanoparticles/ionic liquid/carbon paste electrode (CuO NPs/IL/CPE). The combination of the good conductive 1-hexyl-3-methylimidazolium hexafluorophosphate and CuO nanoparticles resulted in an electrode with attractive properties for the determination of hydrazine in the presence of bisphenol A. The linear dynamic ranges were obtained in the ranges of 0.05–150 and 0.2–175 µM with the detection limits (3sb/m) 0.03 and 0.1 µM for HY and BPA, respectively. High stability, sensitivity, selectivity and reproducibility, fast response, the ease of preparation, and surface renewal made the sensor well suitable for the determination of hydrazine in the presence of bisphenol A, which are important pollutants in the environment. Finally, this new sensor was used for the determination of HY and BPA in some water samples such as river water and wastewater.     

Electrochemical sensor based on f-SWCNT and carboxylic group functionalized PEDOT for the sensitive determination of bisphenol A

A simple,sensitive,and reliable method for the voltammetric determination of bisphenol A(BPA) by using carboxylic group functionalized single-walled carbon nanotubes(f-SWCNT)/carboxylic-functionalized poly(3,4-ethylenedioxythiophene)(PC4) complex modified glassy carbon electrode(GCE) has been successfully developed.The electrochemical behavior of BPA at the surface of the modified electrode is investigated by electrochemical techniques.The cyclic voltammetry results show that the as-prepared electrode exhibits strong catalytic activity toward the oxidation of BPA with a well-defined anodic peak at 0.623 V in PBS(0.1 mol/L,pH 7.0).The surface morphology of the 3D network of composite film is beneficial for the adsorption of analytes.Under the optimized conditions,the oxidation peak current is proportional to BPA concentration in the range between 0.099 and 5.794 μmol/L(R~2 = 0.9989),with a limit of detection of 0.032 μmol/L(S/N = 3).The enhanced performance of the sensor can be attributed to the excellent electrocatalytic property of/-SWCNT and the extraordinary conductivity of PC4.Furthermore,the proposed modified electrode displays high stability and good reproducibility.The good result on the voltammetric determination of BPA also indicates that the asfabricated modified electrode will be a good candidate for the electrochemical determination and analysis of BPA.     

An ultrasensitive fluorescent aptasensor based on truncated aptamer and AGET ATRP for the detection of bisphenol A

Given the gigantic harmfulness of bisphenol A (BPA), a novel and ultrasensitive aptasensor, which employs the truncated BPA aptamer, click chemistry, and activators generated by electron transfer for atom transfer radical polymerization (AGET ATRP), was developed herein for the quantitative determination of BPA. Firstly, hairpin DNAs (hairpins) with a thiol at the 5′ end and an azide group at the 3′ end were conjugated with aminated magnetic beads (MBs) through heterobifunctional cross-linkers. BPA truncated aptamer (ssDNA-A) hybridizes with its complementary single-stranded DNA (ssDNA-B) to form double-stranded DNA. In the presence of BPA, ssDNA-A specifically captures BPA, and then ssDNA-B is released. Subsequently, the ssDNA-B hybridizes with hairpins to expose the azide group near the surface of the MBs. Then, propargyl-2-bromoisobutyrate (PBIB), the initiator of AGET ATRP containing alkynyl group, was conjugated with azide group of hairpins via the Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC). Consequently, a large number of fluorescein-o-acrylate (FA) were introduced to the MBs through AGET ATRP, resulting in that the fluorescence intensity was increased dramatically. Obviously, the fluorescence intensity was especially sensitive to the change of BPA concentration, and this method can be used in quantitative determination of BPA. Under optimal conditions, a broad liner range from 100 fM to 100 nM and a low limit of detection (LOD) of 6.6 fM were obtained. Moreover, the method exhibits not only excellent specificity for BPA detection over BPA analogues but high anti-interference ability in real water sample detection, indicating that it has huge application prospect in food safety and environment monitoring.

     

A mass spectral library based on chemical ionization and collision-induced dissociation

Antibodies were purified from normal rabbit, sheep, goat, rat, human and bovine serum using preparative electrophoresis on a Gradiflow in a single-step process using an asymmetrical cartridge with three different pore size polyacrylamide membranes. Recoveries in each case were over 80% and were higher than those obtained using affinity chromatography on protein A, protein G or protein L. Degree of purity was at least comparable with these methods. These results suggest that preparative electrophoresis can be considered a general method for the purification of research quantities of antibodies from multiple serum sources and may be particularly useful where the reactivity with protein A, G or L is unknown.     

Structure and properties of an hybrid system based on bisphenol A polycarbonate modified by A polyamide 6/organoclay nanocomposite

Blends of poly(carbonate of bisphenol A) (PC) with minute amounts of a nanocomposite based in polyamide 6 (PA6) with a layered organoclay (nPA6) were obtained upon melt mixing by varying the contents of both nPA6 and organoclay. The ternary nanocomposites (NC) were composed of a PC-rich matrix with some mixed PA6 present, and by a neat nPA6 dispersed phase. Upon dissolution of the matrix of the NC’s, the dispersed phase showed a highly fibrillar morphology that resembled that of thermoplastic/liquid crystalline polymer (LCP) blends. The cryogenically fractured surfaces observed by SEM showed a very fine particle size that was attributed to the presence of PA6 in the matrix and indicated a low interfacial tension. The Young’s modulus behaviour is proposed to be a consequence of the slight orientation of the PC-rich matrix and the highly fibrillated and oriented nPA6 dispersed phase. The important reinforcement effect of the dispersed phase is attributed to the additive effects of its large degree of orientation, and the reinforcing effect of the organoclay.     

Photostabilizing of bisphenol A polycarbonate by using UV-absorbers and self protective block copolymers based on resorcinol polyarylate blocks

Bisphenol A polycarbonate degrades due to sunlight, humidity and oxygen. In this study two possible techniques to stabilize the polymer were compared, i.e. blending of UV-absorbers (UVAs) into the polymer or using block copolymers based on resorcinol polyarylates. Combination of different analysis techniques shows that the protection by UVAs is not as good as by the resorcinol polyarylate block copolymers. The block copolymer rearranges itself through a photo-Fries rearrangement within hours into a UV-absorbing top layer. Two different block compositions were studied, and the copolymer with the highest concentration of resorcinol polyarylate groups shows the best protection.     

Syntheses and permselectivity properties of polysulfones based on bisphenol A and 1, 1 bi‐2 naphthol

Polysulfone copolymers based on mixtures of bisphenol A, BPA, and 1,1 bi‐2 naphthol, BN, diols have been synthesized and their gas permeability coefficients and selectivity separation factors for O₂/N₂ and CO₂/CH₄, at 5 atm and 35 °C, have been measured in a standard permeation cell. The polysulfone copolymers can form flexible thin films suitable for gas separation membranes. The gas selectivity for O₂/N₂ measured for the polysulfone copolymers synthesized with 50 and 70 mol % of BN, with the rest being BPA, in the initial mixture of diols are 6.4 and 6.8, respectively. The corresponding gas permeability coefficients for O₂ are 1.24 and 1.09 Barrers. Compared to the corresponding selectivity and permeability balance reported for polysulfones based on pure BPA, BPA–PSF, the copolymers show a balance that moves in the direction of higher selectivity with small losses in the permeability of the fastest gas. From the glass transition temperature determinations, it is observed that the incorporation of BN in the repeating unit of BPA–PSF inhibits large‐scale segmental motions that are reflected in reductions in the diffusivity coefficients for all gases. © 2003 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 226–231, 2004     

A tactically novel alternative to acyclic stereoselection based on the concept of a replicating chiron — access to 1,3-polyols

(S)-Glutamic acid is used as a chiral template to construct seven carbon subunits containing alternating hydroxyl groups with stereochemical control. Enantiomeric and/or diastereomeric 3,5-dideoxy-heptitols are thus obtained.     

A new original approach to the design of anticancer drugs based on energy-rich quadricyclanes

Russian Chemical Bulletin - Quadricyclane derivatives are shown for the first time to be promising for application as anticancer drugs. The efficiency of such cage compounds is mainly due to...     

A novel multi-electrochromic polymer based on selenophene and benzotriazole via electrochemical and chemical polymerization

In this study, a novel donor-acceptor type monomer was designed based on selenophene and benzotriazole with a bulky pendant group and synthesized through Stille coupling reaction. The monomer was polymerized electrochemically by using cyclic voltammetry and also chemically by oxidation in the presence of FeCl₃. Both polymers were then compared in terms of their optical properties, electrochemical and spectroelectrochemical behaviors, kinetic and colorimetric properties and surface morphologies. Independent of the polymerization method, both electrochemically (E-PSeBTz) and chemically polymerized (C-PSeBTz) coatings showed quite similar properties. Both polymers have p-doping character and multichromic properties in their oxidized states. The polymers can be fully switched between their oxidized and neutral states in fairly short times with acceptable optical contrast at different wavelengths. Both polymers exhibit a λ_max of 505?nm and the optical band gaps of the materials were found to be 1.85?eV and 1.80?eV for E-PSeBTz and C-PSeBTz, respectively.