Bisoprolol fumarate is a beta blocker-type drug substance which has been well known for several decades. However, no relevant data can be found in the literature about its crystal polymorphism. The purpose of this paper was to present two anhydrous forms (Form I and Form II) and a hydrate of bisoprolol fumarate substance. Crystalline forms were studied by various solid-state analytical methods: Fourier transform infrared (FT-IR) spectroscopy, X-ray powder diffraction (XRPD), dynamic vapor sorption (DVS) and thermoanalytical methods (thermogravimetry and differential scanning calorimetry). Thermodynamic stability and solubility of the presented polymorphs were also investigated. Both FT-IR and XRPD methods were found to be suitable for the characterization of the different crystal structures. Thermoanalytical measurements showed that (1) Form I and Form II own clearly different melting points and (2) both Form II and hydrate forms can transform into Form I at higher temperature values. Results of the DVS measurements prove that both Form I and Form II became metastable under extremely humid conditions (>?80% RH) and converted into the hydrate. Thermodynamic stability studies showed that Form I and Form II polymorphs are in enantiotropic relationship with an enantiotropic point at about 40–45 °C. Solubility studies indicated that all of the prepared forms are highly soluble, and no difference was found between them. Considering the recommendations of the corresponding International Conference of Harmonization guideline, it can be stated that no specification is required for crystal polymorphism in case of this substance.
We report a novel, fast, and automatic SPME-based method capable of extracting a small molecule-drug conjugate (SMDC) from biological matrices. Our method relies on the extraction of the drug conjugate followed by direct elution into an electrospray mass spectrometer (ESI-MS) source for qualitative and quantitative analysis. We designed a tool for extracting the targeting head of a recently synthesized SMDC, which includes acetazolamide (AAZ) as high-affinity ligand specific to carbonic anhydrase IX. Specificity of the extraction was achieved through systematic optimization. The design of the extraction tool is based on noncovalent and reversible interaction between AAZ and CAII that is immobilized on the SPME extraction phase. Using this approach, we showed a 330% rise in extracted AAZ signal intensity compared to a control, which was performed in the absence of CAII. A linear dynamic range from 1.2 to 25 μg/ml was found. The limits of detection (LOD) of extracted AAZ from phosphate-buffered saline (PBS) and human plasma were 0.4 and 1.2 μg/ml, respectively. This with a relative standard deviation of less than 14% (n = 40) covers the therapeutic range.
N-Heterocyclic carbenes (NHCs, :C ) can interact with azolium salts ( C−H+ ) by either forming a hydrogen-bonded aggregate ( CHC+ ) or a covalent C−C bond ( CCH+ ). In this study, the intramolecular NHC–azolium salt interactions of aromatic imidazolin-2-ylidenes and saturated imidazolidin-2-ylidenes have been investigated in the gas phase by traveling wave ion mobility mass spectrometry (TW IMS) and DFT calculations. The TW IMS experiments provided evidence for the formation of these important intermediates in the gas phase, and they identified the predominant aggregation mode (hydrogen bond vs. covalent C−C) as a function of the nature of the interacting carbene–azolium pairs. 相似文献
The topology of the molecular electron density of benzene dithiol gold cluster complex Au4−S−C6H4−S′−Au′4 changed when relativistic corrections were made and the structure was close to a minimum of the Born–Oppenheimer energy surface. Specifically, new bond paths between hydrogen atoms on the benzene ring and gold atoms appeared, indicating that there is a favorable interaction between these atoms at the relativistic level. This is consistent with the observation that gold becomes a better electron acceptor when relativistic corrections are applied. In addition to relativistic effects, here, we establish the sensitivity of molecular topology to basis sets and convergence thresholds for geometry optimization. 相似文献
Applied Biochemistry and Biotechnology - A capacitive sensor was developed to analyze the presence and enzymatic activity of a model protease from standard solutions by following the degradation of... 相似文献
The objective of this work is to explore approaches to enhance electrochemical signals through sequential deposition and capping of gold particles. Gold nanoparticles are electrodeposited from KAuCl4 solution under potentiostatic conditions on glassy carbon substrates. The number density of the nanoparticles is increased by multiple deposition steps. To prevent secondary nucleation processes, the nanoparticles are isolated after each potentiostatic deposition step by self‐assembled monolayers (SAMs) of decanethiol or mercaptoethanol. The increasing number of particles during five deposition/protection rounds is monitored by assembling electroactive SAMs using a ferrocene‐labeled alkanethiol. A precise estimation of the surface area of the gold nanoparticles by formation of an oxide layer on gold is difficult due to oxidation of the glassy carbon surface. As an alternative approach, the charge flow of the electroactive SAM is used for surface measurement of the gold surface area. A sixfold increase in the redox signal in comparison to a bulk gold surface is observed, and this increase in redox signal is particularly notable given that the surface area of the deposited nanoparticles is only a fraction of the bulk gold surface. After five rounds of deposition there is a gold loading of 1.94 μg cm?2 of the deposited nanoparticles as compared to 23.68 μg cm?2 for the bulk gold surface. Remarkably, however, the surface coverage of the ferrocene alkanethiol on the bulk material is only 10 % of that achieved on the deposited nanoparticles. This enhancement in signal of the nanoparticle‐modified surface in comparison to bulk gold is thus demonstrated not to be attributable to an increase in surface area, but rather to the inherent properties of the surface atoms of the nanoparticles, which are more reactive than the surface atoms of the bulk material. 相似文献
New auride Ca3Au3In was synthesized from the elements in a sealed tantalum tube in a high‐frequency furnace. Ca3Au3In was investigated by X‐ray powder and single crystal diffraction: ordered Ni4B3 type, Pnma, a = 1664.1(6), b = 457.3(2), c = 895.0(3) pm, wR2 = 0.0488, 1361 F2 values, and 44 variables. The three crystallographically independent boron positions of the Ni4B3 type are occupied by the gold atoms, while the four nickel sites are occupied by calcium and indium in an ordered manner. All gold atoms have trigonal prismatic coordination, i.e. Ca6 prisms for Au1 and Au2 and Ca4In2 prisms for Au3. While the Au3 atoms are isolated, we observe Au1–Au1 and Au2–Au2 zig‐zag chains at Au–Au distances of 292 and 284 pm. These slabs resemble the CrB type structure of CaAu. Consequently Ca3Au3In can be considered as a ternary auride. Together the Au2, Au3 and indium atoms build up a three‐dimensional [Au2In] polyanionic network (281–293 pm Au–In) in which the chains of Au1 centered trigonal prisms are embedded. The crystal chemical similarities with the structures of Ni4B3, CaAuIn, and CaAu are discussed. 相似文献
Crystal structure of the compound entitled 2-methylamino-5-[(5-methyl-2-benzoxazolinone-3-yl)methyl]-1,3,4-thiadiazole dihydrophosphate
is determined using X-ray analysis and compared with the structure obtained from semiempirical and RHF methods at various
levels of theory. RHF/6-31G(d) calculations offer the best conformity with X-ray results for bond lengths and bond angles.
Moreover, at the result of the comparison of various combinations of basis sets and methods, it appears that there is not
much gain in accuracy by using sophisticated methods. 相似文献