Relative alkali-cation affinity of polyoxyethylene (POE) dodecylethers in gas phase was studied by electrospray ionization (ESI) mass spectrometry using dodecylether-poly-ethoxylate (C(12)EO:n, "n" denotes ethyleneoxide unit number) nonionic surfactants, and possible helical conformations of the cationized molecules were demonstrated. The alkali-cation affinity highly depended on the cation diameters. The mass spectra of C(12)EO:8 cationized by alkali-metal ions were dominated by potassiated molecules. The results indicated that the POE moiety could have specific affinity to K(+) ions based on a host-guest interaction between POE helix and potassium ions. This is very similar to the relationships between 18-crown-6 and K(+). The ESI mass spectra exhibited the multiply cationized C(12)EO:n in addition to the singly cationized molecules. The critical EO unit numbers necessary for producing the multiply-charged cationized molecules also depended on the cation diameters. In addition, the POE surfactants highly preferred alkali cations to proton. The results were strongly supported by molecular mechanics/dynamics calculations. A helical conformation of the POE moiety of C(12)EO:15 including two K(+) ions gave a potential minimum, while a lowest energy structure of the protonated molecule took irregular conformations due to the formation of local hydrogen bonds. 相似文献
The protonation states of buried histidine residues in human deoxyhemoglobin were unambiguously identified by using a neutron crystallographic technique. Unexpectedly, the neutron structure reveals that both the alpha- and beta-distal histidines (Hisalpha58 and Hisbeta63) adopt a positively charged, fully (doubly) protonated form, suggesting their contribution to the Bohr effect. In addition, the neutron data provide an accurate picture of the alpha1beta1 hydrogen-bonding network and allow us to observe unambiguously the nature of the intradimeric interactions at an atomic level. 相似文献
The miscibility of a drug with excipients in solid dispersions is considered to be one of the most important factors for preparation of stable amorphous solid dispersions. The purpose of the present study was to elucidate the feasibility of (1)H-NMR spin-lattice relaxation measurements to assess the miscibility of a drug with excipients. Solid dispersions of nifedipine with the hydrophilic polymers poly(vinylpyrrolidone) (PVP), hydroxypropylmethylcellulose (HPMC) and alpha,beta-poly(N-5-hydroxypentyl)-L-aspartamide (PHPA) with various weight ratios were prepared by spray drying, and the spin-lattice relaxation decay of the solid dispersions in a laboratory frame (T(1) decay) and in a rotating frame (T(1rho) decay) were measured. T(1rho) decay of nifedipine-PVP solid dispersions (3 : 7, 5 : 5 and 7 : 3) was describable with a mono-exponential equation, whereas T(1rho) decay of nifedipine-PHPA solid dispersions (3 : 7, 4 : 6 and 5 : 5) was describable with a bi-exponential equation. Because a mono-exponential T(1rho) decay indicates that the domain sizes of nifedipine and polymer in solid dispersion are less than several nm, it is speculated that nifedipine is miscible with PVP but not miscible with PHPA. All the nifedipine-PVP solid dispersions studied showed a single glass transition temperature (T(g)), whereas two glass transitions were observed for the nifedipine-PHPA solid dispersion (3 : 7), thus supporting the above speculation. For nifedipine-HPMC solid dispersions (3 : 7 and 5 : 5), the miscibility of nifedipine and HPMC could not be determined by DSC measurements due to the lack of obviously evident T(g). In contrast, (1)H-NMR spin-lattice relaxation measurements showed that nifedipine and HPMC are miscible, since T(1rho) decay of the solid dispersions (3 : 7, 5 : 5 and 7 : 3) was describable with a mono-exponential equation. These results indicate that (1)H-NMR spin-lattice relaxation measurements are useful for assessing the miscibility of a drug and an excipient in solid dispersions. 相似文献
The environmentally active molecule nitrogen dioxide (NO2) has been systematically studied using high level theoretical methods. The electronic ground state and the low-lying quartet states of NO2 have been investigated. Single reference restricted open-shell self-consistent field (SCF), complete active space SCF (CASSCF), spin-restricted (R) and spin-unrestricted (U) configuration interaction with single and double excitations (CISD), coupled cluster with single and double excitations (CCSD), CCSD with perturbative triple excitations [CCSD(T)], and internally contracted multireference configuration interaction (ICMRCI) methods along with Dunning's correlation consistent polarized valence cc-pVXZ and augmented cc-pVXZ (where X=T,Q,5) basis sets were used in this research. At the aug-cc-pV5Z/UCCSD(T) level the classical adiabatic excitation energies (Te values) of the three lowest-lying quartet excited states were predicted to be 83.3 kcalmol (3.61 eV, 29 200 cm(-1)) for the ? 4A2 state, 93.3 kcalmol (4.05 eV, 32 600 cm(-1)) for the b 4B2 state, and 100.8 kcalmol (4.37 eV, 35 300 cm(-1)) for the c 4A1 state. The quantum mechanical excitation energies (T 0 values) were determined to be 81.6 kcalmol (3.54 eV, 28 500 cm(-1)) for the a 4A2 state and 90.7 kcalmol (3.93 eV, 31 700 cm(-1)) for the b 4B2 state. The lowest quartet linear Renner-Teller 4Pi state gives rise to the a 4A2 state with 112.8 degrees and the b 4B2 state with 124.4 degrees <(ONO) bond angles upon bending. The b state shows some peculiar behavior. Although CASSCF, RCISD, UCISD, RCCSD, UCCSD, and RCCSD(T) methods predicted the presence of a Cs equilibrium geometry (a double minimum 4A' state), SCF, UCCSD(T), and ICMRCI wave functions predicted the C2v structure for the b 4B2 state. The importance of both dynamical and nondynamical correlation treatments for the energy difference between C2v and Cs structures of b state is highlighted in this context. The c 4A1 state is predicted to have a very small bond angle of 85.8 degrees . Potential energy diagrams with respect to the bond angles of the ground state and four quartet states are presented. 相似文献
A wide variety of cells usually integrate and respond to the microscale environment, such as soluble protein factors, extracellular matrix proteins, and contacts with neighboring cells. To gain insight into cellular microenvironment design, we investigated two-dimensional microarray formation of endothelial cells on a micropatterned poly(ethylene glycol) (PEG)-brushed surface, based on the relationship between PEG chain density and cellular attachment. The patterned substrates consisted of two regions: the PEG surface that acts as a cell-resistant layer and the exposed substrate surface that promotes protein or cell adsorption. A PEG-brushed layer was constructed on a gold substrate using PEG with a mercapto group at the end of the chain. The density of the PEG-brushed layer increased substantially with repetitive adsorption/rinse cycles of PEG on the gold substrate, allowing marked reduction of nonspecific protein adsorption. These repeated adsorption/rinse cycles were further regulated by using longer (5 kDa) and shorter (2 kDa) PEG to construct PEG layers with different chain density, and subsequent micropatterning was achieved by plasma etching through a micropatterned metal mask. The effects of PEG chain density on pattern formation of cell attachment were determined on micropatterning of endothelial cells. The results indicated that cell pattern formation was strongly dependent on the PEG chain density and on the extent of protein adsorption. Notably, a PEG chain density high enough to inhibit outgrowth of endothelial cells from the cell-adhering region in the horizontal direction could be obtained only by employing formation of a short filler layer of PEG in the preconstructed longer PEG-brushed layer, which prevented nonspecific protein adsorption almost completely. In this way, a completely micropatterned array of endothelial cells with long-term viability was obtained. This clearly indicated the importance of a short underbrushed PEG layer in minimizing nonspecific protein adsorption for long-term maintenance of the active cell pattern. The strategy for cell patterning presented here can be employed in tissue engineering to study cell-cell and cell-surface interactions. It is also applicable for high-throughput screening and clinical diagnostics, as well as interfacing cellular and microfabricated components of biomedical microsystems. 相似文献
The air/liquid interface of 1-alkyl-3-methylimidazolium tetrafluoroborates with the general formula [C(n)mim]BF(4) (n = 4-11) was studied using infrared-visible sum frequency generation (SFG) vibrational spectroscopy. The probability of the gauche defect per CH2-CH2 bond in the alkyl chain decreases as the number of carbon atoms in the alkyl chain increases. This observation suggests that the interaction between the alkyl chains is enhanced as the alkyl chain length becomes longer. The frequencies of the C-H stretching vibrational modes observed in the SFG spectra are higher than those of the corresponding peak positions observed in the infrared spectra of the bulk liquids. This shift is consistent with a structure in which the alkyl chain protrudes from the bulk liquid into the air. A local structure, which originates from the intermolecular interaction between the ionic liquid molecules, is proposed to explain these observations. 相似文献
A highly sensitive simultaneous quantitative method for a cassette cold-microdosing study on celiprolol and atenolol was developed with liquid chromatography-tandem mass spectrometry. The method utilizes a combination of solid-phase extraction (SPE) with strong cation exchange (SCX) cartridge columns and reversed-phase chromatography with an ODS analytical column. SCX-SPE cartridge columns (100 mg sorbent) were used for a selective extraction of celiprolol, atenolol and metoprolol (internal standard) from 500 μL of human plasma samples. Turbo-ion spray at positive mode was employed for the ionization of the drug compounds. Quantitation was performed on a triple quadrupole mass spectrometer by selected reaction monitoring with the transitions of m/z 380 to m/z 251 for celiprolol and m/z 267 to m/z 145 for atenolol. Separation of analytes was achieved on an ODS column (100 mm length × 2.1 mm id, 3 μm) by a gradient elution with 10 mM formic acid and methanol by varying their proportion at a flow rate of 0.2 mL/min. The method was validated in the range of 1-250 pg/mL for celiprolol and 2.5-250 pg/mL for atenolol and was successfully applied to the elucidation of pharmacokinetic profiling in a cold cassette microdosing study of the β-blockers. 相似文献
A novel oligonucleotide carrier which can scavenge ROS is described. The synthesized graft polymer is composed of a PEG segment and a TEMPO‐containing hydrophobic segment for scavenging ROS. This graft polymer can form a PIC through electrostatic interaction with oligonucleotides such as siRNA. The amount of ROS was monitored by fluorescence measurements using H2DCFDA as a probe, and it was confirmed that the ROS level was effectively suppressed. The cellular uptake of PIC containing the fluorescence‐labeled oligonucleotide was evaluated by fluorescence microscopy. Delivered siRNA suppressed the expression of the mRNA. The prepared graft copolymer is thus a promising candidate as a novel oligonucleotide carrier which also reduces ROS damage generated by cationic polymer carriers.