Liquid chromatographic assay of phenothiazine, thioxanthene and butyrophenone neuroleptics and antihistamines in blood and plasma with conventional and radial compression columns and UV and electrochemical detection

An assay strategy for determining a wide range of phenothiazine, thioxanthene and butyrophenone neuroleptics and antihistamines both alone and in combination in blood and plasma is described. The general method employs liquid chromatography with both conventional and radial compression nitrile bonded columns. Detection is by ultraviolet absorption spectrophotometry or by amperometry depending on the concentrations to be measured. Ultraviolet absorption is suitable down to 10 ng/ml. Below this level amperometry is preferable. The various compounds are used as internal standards for each other. The lower limit of detection is approximately 0.1 ng ml-1 with 10-ml sample. The with-run coefficient of variation is a maximum of 7.3%.     

Simultaneous spectrophotometric determination of molybdenum and selenium,and of molybdenum and tellurium

A method is reported for the extraction of molybdenum-phenylfluorone by chloroform. The extraction is complete whether perchlorate ions are present or not but the extractions in the presence of perchlorate ions gave a somewhat more sensitive procedure for the spectrophotometric determination of molybdenum in the solvent phase as the molybdenum-phenylfluorone complex.A procedure is reported for the simultaneous determination of molybdenum and selenium, and molybdenum and tellurium. The method involves first the formation and solvent extraction of the molybdenum-phenylfluorone complex by chloroform in the presence of perchlorate ions, followed by determination of selenium in the remaining aqueous phase as selenium-diethyldithiocarbamate complex after solvent extraction with 2-ethyl-1-hexanol in the presence of perchlorate ions. A similar procedure is reported for the simultaneous determination of molybdenum and tellurium except that in the determination of molybdenum, the phenylfluorone complex is extracted by chloroform in the absence of perchlorate ions. Tellurium is determined in the remaining aqueous phase as tellurium-diethyldithiocarbamate complex after solvent extraction by 2-ethyl-1-hexanol solvent extraction in the presence of perchlorate ions.     

Sizes of atoms and ions and covalency of bonding in molecules and crystals

A new system of atomic radii for the elements up to barium inclusive is constructed. Values of the radii are chosen so as the dependence between the dissociation energy of diatomic homonuclear molecules and a depth of atom overlapping is monotonous, and the scatter of data is minimal. The depth of overlapping is calculated as a difference between the sum of atomic radii and an experimental interatomic distance. Conclusions are made that: the radii of free atoms and ions are determined by the value of the electron density equal to 0.01 au; they considerably change in molecules and crystals only as a result of the charge transfer from cation to anion; covalent bonding is well described by the overlapping of free atoms (ions), confined by the surface of the given radius, and its energy depends upon the depth of overlapping of valence electron densities of atoms. A method of overlapping atoms is proposed for the approximate estimation of ionic sizes and charges in bound systems.     

Ground- and excited-state aromaticity and antiaromaticity in benzene and cyclobutadiene

The aromaticity and antiaromaticity of the ground state (S 0), lowest triplet state (T 1), and first singlet excited state (S 1) of benzene, and the ground states (S 0), lowest triplet states (T 1), and the first and second singlet excited states (S 1 and S 2) of square and rectangular cyclobutadiene are assessed using various magnetic criteria including nucleus-independent chemical shifts (NICS), proton shieldings, and magnetic susceptibilities calculated using complete-active-space self-consistent field (CASSCF) wave functions constructed from gauge-including atomic orbitals (GIAOs). These magnetic criteria strongly suggest that, in contrast to the well-known aromaticity of the S 0 state of benzene, the T 1 and S 1 states of this molecule are antiaromatic. In square cyclobutadiene, which is shown to be considerably more antiaromatic than rectangular cyclobutadiene, the magnetic properties of the T 1 and S 1 states allow these to be classified as aromatic. According to the computed magnetic criteria, the T 1 state of rectangular cyclobutadiene is still aromatic, but the S 1 state is antiaromatic, just as the S 2 state of square cyclobutadiene; the S 2 state of rectangular cyclobutadiene is nonaromatic. The results demonstrate that the well-known "triplet aromaticity" of cyclic conjugated hydrocarbons represents a particular case of a broader concept of excited-state aromaticity and antiaromaticity. It is shown that while electronic excitation may lead to increased nuclear shieldings in certain low-lying electronic states, in general its main effect can be expected to be nuclear deshielding, which can be substantial for heavier nuclei.     

Cellulose and chitin esters,and the reactivity of cellulose and chitin

Summary On comparison of the reactivities of chitin and cellulose in their conversion into ethers and esters it is found that chitin is considerably less reactive than cellulose, which is to be attributed to a difference in the internal active surfaces.Paper read at a General Meeting of the Division of Chemical Sciences, Academy of Sciences, USSR, Moscow, March 10, 1961     

Hard and soft acids and bases: structure and process

Under investigation is the structure and process that gives rise to hard-soft behavior in simple anionic atomic bases. That for simple atomic bases the chemical hardness is expected to be the only extrinsic component of acid-base strength, has been substantiated in the current study. A thermochemically based operational scale of chemical hardness was used to identify the structure within anionic atomic bases that is responsible for chemical hardness. The base's responding electrons have been identified as the structure, and the relaxation that occurs during charge transfer has been identified as the process giving rise to hard-soft behavior. This is in contrast the commonly accepted explanations that attribute hard-soft behavior to varying degrees of electrostatic and covalent contributions to the acid-base interaction. The ability of the atomic ion's responding electrons to cause hard-soft behavior has been assessed by examining the correlation of the estimated relaxation energies of the responding electrons with the operational chemical hardness. It has been demonstrated that the responding electrons are able to give rise to hard-soft behavior in simple anionic bases.     

Electronic and Magnetic Properties of Linear and Dimerized Titanium Nanochains Under Compressive and Tensile Strain

The magnetic and electronic properties of both linear and dimerized nanochains of titanium at different atomic distances are calculated within density functional theory with the generalized gradient approximation. Titanium which is a nonmagnetic in its bulk form is shown to become magnetic in its nanochain structure. Also, a close relationship is found between magnetic state and geometry of chain structure and the dependence of electronic properties on the atomic structures of chains is revealed. It is found that, for dimerized nanochains from equilibrium constant, compressive strain leads to a reduction in magnetism. Moreover, characteristics of the systems near the Fermi level are investigated and the charge densities of both nanostructures are studied in the ferromagnetic order. The results show that metallic bonding is mainly responsible for the linear structure; however, for the dimerized structure, the bonding is more directional, i.e. has a more covalent character. With increasing tension along the axis of the nanostructures, a change in the types of bonding is found.     

Direct and sensitized photoprocesses of bis-benzimidazole dyes and the effects of surfactants and DNA

The photoprocesses of two bis-benzimidazole dyes, Hoechst 33258 (1) and an analog, where the phenolic group in p-position is replaced by an ethoxy group, Hoechst 33342 (2), were studied. For 1 and 2 in aqueous solution the quantum yield of fluorescence is strongly pH dependent; it decreases from a maximum value of phi f = 0.4 at pH 5 to phi f = 0.02 at pH 8. The effects of absorption and fluorescence, induced by sodium dodecyl sulfate surfactants below and above the critical micelle concentration and by double-stranded DNA, are interpreted by assuming that in bulk aqueous solution the dyes are essentially present as monomers. The strong enhancement of phi f, when the dye is bound to double-stranded DNA or solubilized in micelles, is suggested to be due to different environments at the benzimidazole rings. A quinoid intermediate with absorption maximum at 380 nm is formed for 1 at neutral pH using lambda exc = 248 or 308 nm. N-centered radicals of 1 or 2 in aqueous solution were observed by laser flash photolysis after electron ejection using wavelengths of 193 or 248 nm (mono and biphotonic, respectively). The precursor radical cation escaped observation but is transformed into the above radicals by deprotonation. Electron transfer from 1 in aqueous solution to triplet acetone takes place, and subsequent deprotonation is proposed to yield N-centered radicals. In addition, energy transfer from acetone to 1 is suggested, leading to T-T absorption with the maximum at 700 nm. The photoprocesses are discussed and the results compared with those known from pulse radiolysis.     

Sarin and Soman: Structure and Properties

The most stable conformers of sarin (isopropyl methylphosphonoflouridate) and soman (pinacolyl methylphosphonofluoridate) are determined in high-level-correlated calculations with extended Gaussian basis sets. The two molecules are found to have three low-energy conformers each. For both molecules two of the lowest energy conformers have almost the same energies with a very small barrier separating the corresponding minima. The third conformer of sarin is found to lie about 1 kcal/mol above the lowest energy form. For soman the corresponding value is equal to about 4 kcal/mol. The significance of these data for the mechanism of the toxic action of sarin and soman is discussed. According to our investigations sarin and soman are highly similar electronically and differences in their features arise mostly from the size and spatial arrangement of the alkoxy substituent at phosphorus. Also the influence of solvents on the conformations and solvation energies of sarin and soman is investigated.     

Progress and prospects in on-line-process gas and liquid chromatography

The present status of both process gas (PGC) and liquid (PLC) chromatographs is examined with regard to the main criteria that any process analyser should fulfil: reliability, credibility, fast response and low maintenance. Despite considerable improvements in the construction of these instruments, owing to the materials used, progress in technology and microelectronics and the advent of microprocessors, their reliability is still a matter of great concern.The deferred standard concept may offer a solution for these problems. Progress is also made by the introduction of fused-silica capillary columns in PGC, which allow a better resolution and a greater speed of analysis. However, this technology requires a redesign of PGCs.Further, particularly for PLC, a new approach based on the concept of instability instead of stability of the main parameters is proposed. This approach leads to a simpler, more reliable and less expensive PLC. The consequence is some radical changes in the design and functions of both the analytical and control units of the chromatograph. The analytical unit is plugged into the chemical reactor and is not temperature controlled. The control unit, incorporating a microcomputer and dedicated software, is able to characterize the peaks despite their fluctuating retention times, to readjust the time functions of the analytical sequence and to validate the detector response in the case of fluctuations of temperature or mobile phase flow-rate. This approach is useful for the implementation of temperature programming and, according to the validation function of the deferred standard, to allow the use of selective but unstable detectors in PGC.Simpler in hardware, PGCs and PLCs could become “intelligent apparatus” capable of new qualitative and quantitative tasks at a more competitive cost.     

Polyhydroxyl-based surfactants and their physico-chemical properties and applications

This contribution deals with the physical-chemical properties of surfactants carrying hydroxyl groups in the polar part. Topics discussed include surface and colloid properties, micelles (both single and multi-component), general phase behaviour and microemulsions. A general conclusion is that our understanding of polyhydroxy surfactants is increasing, but that further work is needed to unravel certain aspects of this important class of surfactants. Examples of such aspects are the origin of the liquid-liquid phase separation and the adsorption to solid surfaces of polyhydroxy surfactants.     

Determination of lanthanides and yttrium in rocks and minerals by atomic-absorption and flame-emission spectrometry

The sensitivity of atomic-absorption and flame-emission determination of lanthanides and yttrium is improved by a factor of 2-5 when an absolute ethanol solution of the perchlorate of the metal (instead of an aqueous solution) is aspirated into a nitrous oxide-acetylene flame. Based on this, a method has been developed for accurate determination of small amounts of certain rare earths and yttrium. Lanthanum (1%) is used as a spectroscopic buffer to eliminate interferences and to enhance the sensitivities in certain determinations. Where the use of lanthanum is not practicable because of interferences (such as in the determination of praseodymium and samarium by flame emission), sodium (2000 ppm) is used as the spectroscopic buffer. Studies with synthetic solutions indicate that yttrium and most lanthanides can be directly determined in minerals without any chemical separation. With rock samples it is necessary to preconcentrate the traces of the rare earths by fluoride or oxalate precipitation with calcium as the carrier, followed by removal of calcium by hydroxide precipitation using mg amounts of iron as the carrier. The method developed has been applied to the determination of certain lanthanides and yttrium in a variety of rocks, including the Canadian reference rocks, syenites SY-1, SY-2 and SY-3, and some minerals such as britholite, cenosite, chevkinite, allanite, apatite and sphene.     

Electronic structure and polarizability of ortho-benzoquinonediimine and its singly and doubly charged anions

The results of electronic structure calculations for o-benzoquinonediimine and its singly and doubly charged anions are presented. The variation of the geometrical and valence structures due to electron addition to the molecule is analyzed, and electron affinity is estimated. Polarizabilities of the neutral molecule and singly charged anion are calculated. The influence of the basis on the results of polarizability calculations for molecular anions is investigated. Translated from Zhumal Struktumoi Khim ii, Vol. 41, No. 1, pp. 34-41, January–February, 2000.     

Walk counts, labyrinthicity, and complexity of acyclic and cyclic graphs and molecules

It is demonstrated how the complexity of a (molecular) graph can be quantified in terms of the walk counts, extremely easily obtained graph invariants that depend on size, branching, cyclicity, and edge and vertex weights (unsaturation, heteroatoms). The influence of symmetry is easily accounted for. The term labyrinthicity is proposed for what is measured by walk counts alone, neglecting symmetry. The total walk count and recently advanced measures of labyrinthicity or complexity are compared with respect to the ordering of structures and to the computational effort required to obtain numerical values.     

Separation and determination of mixtures containing p-aminosaucylic add and m-aminophenol

A procedure is described for separating and determining p-anunosalicylie add and m-aminophenol m mixtures. Separation is effected by passing a solution of the mixture in dimethylformamide through a column of strong cation-exchange resin. The eluate containing the p-aminosalicylic acid is titrated with sodium methoxide. The m-aminophénol is eluted from the column with ethanolic HC1. The eluate is evaporated to dryness, the residue dissolved in acetic acid, and the solution titrated with perchloric add.     

Cryptands and bismacrocycles with cyanuric and isocyanuric units: synthesis and structural investigations

Hay synthesis of cryptands and bismacrocycles starting from tripodands with cyanuric and isocyanuric cores is reported. The structure of the compounds is revealed by X-ray diffraction, NMR spectrometry and MS investigations. DNMR experiments carried out with bismacrocycles indicated the flipping of the rings and the free-energy barrier for the conformational process could be determined in one case.     

Tetradehydroadamantane-1,3,5,7-di- and tetracations and their helium and hydride inclusion complexes: spherical aromaticity and evidence for a bonding interaction between carbon and helium

The unusual stability of the experimentally known 1,3-dehydro-5,7-adamantyl dication was previously explained by four-center two-electron aromaticity with three-dimensional (tetrahedral) topology. Magnetic criteria (ACID and ring-current analysis) now demonstrate that there is also a very strong contribution from hyperconjugation with all six methylene bridges. The delocalized system of electrons thus includes all valence electrons, and the structure, therefore, should rather be described as a spherically aromatic 50-electron system. The corresponding Td-symmetric tetracation with 48 electrons is antiaromatic and not a minimum structure. With a He atom or a hydride ion at the center of the cage, the tetracation is predicted to form a kinetically stable complex. Magnetic criteria demonstrate that the antiaromaticity is greatly reduced, and a bond analysis hints at bonding interactions between He (and H-) and the carbon atoms of the adamantane cage.     

A configurational and conformational study of aframodial and its diasteriomers via experimental and theoretical VA and VCD spectroscopies

In this work we present the experimental and theoretical vibrational absorption (VA) and the theoretical vibrational circular dichroism (VCD) spectra for aframodial. In addition, we present the theoretical VA and VCD spectra for the diasteriomers of aframodial. Aframodial has four chiral centers and hence has 2⁴ = 16 diasteriomers, which occur in eight pairs of enantiomers. In addition to the four chiral centers, there is an additional chirality due to the helicity of the entire molecule, which we show by presenting 12 configurations of the 5S,8S,9R,10S enantiomer of aframodial. The VCD spectra for the diasteriomers and the 12 configurations of one enantiomer are shown to be very sensitive not only to the local stereochemistry at each chiral center, but in addition, to the helicity of the entire molecule. Here one must be careful in analyzing the signs of the VCD bands due to the ‘non-chiral’ chromophores in the molecule, since one has two contributions; one due to the inherent chirality at the four chiral centers, and one due to the chirality of the side chain groups in specific conformers, that is, its helicity. Theoretical simulations for various levels of theory are compared to the experimental VA recorded to date. The VCD spectra simulations are presented, but no experimental VCD and Raman spectra have been reported to date, though some preliminary VCD measurements have been made in Stephens’ lab in Los Angeles. The flexible side chain is proposed to be responsible for the small size of the VCD spectra of this molecule, even though the chiral part of the molecule is very rigid and has four chiral centers. In addition to VCD and Raman measurements, Raman optical activity (ROA) measurements would be very enlightening, as in many cases bands which are weak in both the VA and VCD, may be large in the Raman and/or ROA spectra. The feasibility of using vibrational spectroscopy to monitor biological structure, function and activity is a worthy goal, but this work shows that a careful theoretical analysis is also required, if one is to fully utilize and understand the experimental results. The reliability, reproduceability and uniqueness of the vibrational spectroscopic experiments and the information which can be gained from them is discussed, as well as the details of the computation of VA, VCD and Raman (and ROA) spectroscopy for molecules of the complexity of aframodial, which have multiple chiral centers and flexible side chains. Festschrift in Honor of Philip J. Stephens’ 65th Birthday.