Determination of minor conformational changes of a doxorubicin-peptide conjugate under chromatographic conditions

Thermodynamic analysis of the reversed-phase retention behavior of a doxorubicin-peptide conjugate demonstrated that the degree of non-linearity observed in Van't Hoff plots was impacted by mobile phase acetonitrile content over the 25-38% acetonitrile (v/v) range tested. Small decreases in the non-polar surface area of the doxorubicin-peptide conjugate as a function of temperature were estimated from these data using linear solvent strength relationships, suggesting that the retention behavior may be the result of minor analyte conformational changes during the chromatographic experiment. This hypothesis was supported via circular dichroism (CD), Raman and 1H NMR spectroscopic studies of the doxorubicin-peptide conjugate in selected chromatographic mobile phase compositions. The CD and Raman data indicated small changes to the apparent analyte microenvironment as a function of temperature and bulk solvent environment, while 1H NMR studies specifically demonstrated the environmental sensitivity of protons on three non-polar peptide residues and the proximal aromatic region of the analyte. Together, these data suggest that minor changes to the conformational order of the essentially random structure of the doxorubicin-peptide conjugate are sufficient to impact chromatographic performance.     

Investigations into the chromatographic behaviour of silica gels produced from ester silicates

Summary Silica gels produced from ester silicates (ES-gels) are excellent chromatographic supports. In comparison with other silica gels the RP-materials obtained from them show little peak tailing even with polar, and, in particular, with basic compounds. Gels produced by various manufacturing processes have been classified by adsorption with methyl pyridinium chloride. ES-gels yield very low methyl pyridinium chloride values and small asymmetry parameters. The results indicate that there are strongly acidic, structurally-related surface centres which cause peak tailing on most commercial gels. It was shown that surface silanols on silica gels do not, in themselves, lead to peak tailing.     

Investigations into a vessel of the Cyclades

Summary A Cyclade marble vessel has been investigated with regard to its content of fatty acids. TLC and GC techniques have been employed. Archaeological interpretation of the results is presented.Dedicated to Prof. Dr. G. Schulze on the occasion of his 60th birthday     

Nucleophilic behavior of DBU in a conjugate addition reaction

Reaction of DBU with a diarylpyrone results in 1,4 addition of the DBU and subsequent fragmentation of the DBU moiety into an aminopropyl caprolactam. Incorporation of the fragmented DBU into the diarylpyridone is postulated to occur by an addition/elimination pathway.     

Investigations on the chromatographic behavior of hybrid reversed-phase materials containing electron donor-acceptor systems. I. Contribution of sulfur-aromatic interactions

The influence of sulfur-aromatic interactions on the chromatographic separation behavior of hybrid RP phases, containing thiol-groups and/or embedded sulfide-groups (S-RP) has been investigated. To allow a precise outline of this new interaction mode, a wide variety of S-RP phases with different alkyl chain length, with and without residual thiol-groups and silanol-endcapping were prepared and tested in comparison to some conventional monomerical as well as polymerical n-alkyl type RP phases. The solute test sets employed in this study comprised the classical chromatographic column tests from Engelhardt and Tanaka as well as test assemblies containing polycyclic aromatic hydrocarbons, stilbene-based cis/trans isomers and functional isomers of benzene. In general, a pronounced strong planar recognition ability as well as a strong increase in the retention for aromatic compounds have been noticed. It was furthermore found that not only the sulfur atom incorporated into the alkyl chain, but also the residual thiol-groups of the 3-propylthiol silica backbone contribute to the overall retention behavior of these novel S-RP type phases.     

Investigations on the chromatographic behavior of hybrid reversed-phase materials containing electron donor-acceptor systems. II. Contribution of pi-pi aromatic interactions

The chromatographic behavior of three naphthalimide-type stationary phases were elucidated in terms of hydrophobic, silanophilic and pi-pi interaction properties, employing besides common chromatographic column test methods from Engelhardt and Tanaka, also new test mixtures of geometrical and functional aromatic isomers. It was found that the presence of electron donor/acceptor moieties within a reversed phase system did not only increase the overall retention times for aromatic solutes, but also lead to an enhanced shape selectivity of the hybrid stationary phase. In this context, shape discrimination is primarily based on the number of accessible pi-electrons for pi-pi interaction with the embedded electron deficient ligand moieties. The most outstanding results were obtained for the 1,4,5,8-naphthalenediimidic selector with its horizontal arrangement on the silica surface, which enables a direct face-to-face pi-pi interaction with aromatic solutes, with only little hydrophobic contribution.     

Investigations into a free radical-mediated 1,2-imino migration

The radical reactions of a series of bromides 9a-c and selenides 12-15 have been investigated to determine the factors that are important for a successful radical-mediated 1,2-imino migration.     

Investigations into synthetic phytohormones

Conclusions Trialkylsilyl esters of ring-substituted aryloxyacetic acids have been prepared for the first time, and their PMR and IR spectra studied.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 5, pp. 1132–1134, May, 1977.     

Investigations into the synthesis of amine-linked neodisaccharides

Six tail-to-tail amine-linked neodisaccharides were synthesised as potential glycomimetics. Primary-primary linked compounds were synthesised using Mitsunobu chemistry with glucose-6-sulfonamides as nucleophiles and primary carbohydrate alcohols as electrophiles. Primary-secondary linked compounds were synthesised by epoxide ring opening with carbohydrate 6-amines. Deprotection of all neodisaccharides was carried out using dissolving metal reduction.     

Aromatic hydrocarbon metabolites in fish: automated extraction and high-performance liquid chromatographic separation into conjugate and non-conjugate fractions

An automated extractor-concentrator was used to extract metabolites of naphthalene, 2,6-dimethylnaphthalene, and benzo[a]pyrene from serum, bile and liver homogenate of rainbow trout (Salmo gairdneri). The extracts were analyzed by reversed-phase high-performance liquid chromatography (HPLC) with fluorescence detection. Recoveries of naphthalene and 2,6-dimethylnaphthalene metabolites from all matrices were generally greater than 90%; however, the recoveries of benzo[a]pyrene metabolites from serum ranged from 37-99%. In addition, conjugated metabolites of polycyclic aromatic hydrocarbons (PAHs) were separated from non-conjugated metabolites and parent PAHs by using two diol columns with normal-phase HPLC. The extraction and separation techniques were also applied to isolate metabolites in samples from fish fed 2,6-dimethylnaphthalene.     

Investigations into the Aqueous Synthesis of Selenoglycoconjugates

Glycosylation of bioactive molecules has been found to improve the pharmacokinetic properties of the parent molecule. However, their syntheses often require tedious protecting group manipulations. The development of methodologies which allow direct aqueous conversion of unprotected sugars into glycosides is therefore an ambitious goal. Herein, we present a broadly applicable method for the synthesis of selenoglycosides in water. We show the ease of direct conjugation of unprotected glycosyl diselenides with various biomolecules, including resorcinol, resveratrol, and the antitumor agent, gimeracil, furnishing the corresponding selenoglycoconjugates in up to 96 % yield. We also demonstrate the oxidatively-triggered release of the bioactive drug from the sugar, priming these molecules for medicinal applications. The generality and broad substrate scope of this novel transformation will provide access to various selenium-containing glycomimetics and glycoconjugates.     

Investigations into the Manzamine Alkaloid Biosynthetic Hypothesis

The biomimetic synthesis of a pentacyclic alkaloid (keramaphidin B, 1 ), an intermediate in the biogenetic pathway to the manzamine alkaloids, has been achieved. Compound 1 was formed by an intramolecular Diels–Alder reaction of macrocycle 2 in buffer followed by reduction with NaBH₄. This reaction provides the first direct expeimental evidence for the authors' biosynthetic hypothesis.     

Investigations into the role of activated carbon in a moisture-blocking cement formulation

Physical deterioration is a natural consequence of moisture attack in finished concrete. Moisture is retained in open voids in prepared cement during mixing and hydration stages. Further atmospheric moisture uptake occurs following dehydration under use conditions in polymer-containing cement formulations, since polymers act as conduits for moisture ingress. The initial attribute of added strength from the polymer in improved cement formulations is thus nullified. Customary solution to the moisture problem has centered around improving moisture resistance by significant reduction of inherent macro defects. A more complete method of moisture blocking by the reaction of activated carbon with a vinyl polymer included in the cement formulation is described here. The moisture blocking action is due to the mitigation of open voids by the occlusion of a carbon-vinyl additive, essentially resulting in filled voids or no voids in the prepared cement, producing a durable finished concrete product. Supporting evidence for the above by thermal, polarization, X-ray and SEM are reported in this paper. This revised version was published online in July 2006 with corrections to the Cover Date.     

Preliminary studies into the direct interfacing of a microreactor to a gas chromatographic instrument

The paper reports on a preliminary study into the coupling of a microreactor to a GC-FID, using a standard GC needle as the interface between the microreactor and the injection port of a conventional GC. Using the injection needle as the ground electrode, electroosmotic flow was used to control the injection of reagent/sample into the GC. Photolithographic and wet etching techniques were used to fabricate the microreactor (channels 200 microns id, 100 microns deep) in a borosilicate glass substrate. The results of the effects of voltage and injection times on the response signal are presented. The critical obstacles to overcome were the backpressure posed by the carrier gas disrupting the liquid flow in the channels and reservoirs of the microreactor and the need to thermally insulate the microreactor, to prevent evaporation of solvent and reagents from the device.     

Thermodynamic behavior of mixed benzodiazepines by a new liquid chromatographic method

Summary Using a rapid chemometric methodology to determine the separation factor, , at different temperatures, Gibbs Helmholtz parameters ( (H), (S), (G)) of two adjacent benodiazepines on a chromatogram were obtained from ln versus T^–1 plots. A temperature dependent reversal of the elution order was studied and the mobile phase composition and column temperature were optimized to obtain the best separation. A flow rate of 0.80 ml min^–1 with 52.6% methanol in the methanol-water mixture and a column temperature of 48°C gave the most efficient separation of ten benzodiazepines.     

Experimental and Theoretical Investigations into the Paratropic Ring Current of a Porphyrin Sheet

Anomalous induced magnetic effects were observed in a directly fused square‐planar porphyrin sheet 1 , in that the protons above the center of the tetraporphyrin core were characteristically shifted downfield in the ¹H NMR spectrum. These observations suggest a rare paratropic ring‐current effect around the planar cyclooctatetraene (COT) core of 1 . To examine the spatial distribution of the induced magnetic effect, face‐to‐face dimeric complexes of porphyrin sheet 1 with bipyridyl‐type guest molecules ( G1 – G3 ) were prepared, which provided complexation‐induced shifts (CISs) of the guest molecules as a neat experimental guide to the distance dependence of the induced magnetic effects in 1 . Nucleus‐independent chemical shift (NICS) values of 1 were calculated by varying the distance of the probe from the plane of 1 . Whereas a simple bell‐type profile was estimated for the complex ( 1 )₂–( G1 )₄, the distance profiles of the CIS became increasingly flat for ( 1 )₂–( G2 )₄ and ( 1 )₂–( G3 )₄. Finally, we investigated the paratropic ring‐current effect just above the COT core of the complex 1 –( G4 )₂, which agrees well with the theoretically estimated distance‐dependent induced magnetic effect. Consequently, both experimental and theoretical studies on the complexes of porphyrin sheets with guest molecules revealed for the first time a unique distance dependence of the paratropic ring current.     

Investigations into the use of a reverse scan in a quadrupole ion trap mass spectrometer

The forward scan (i.e. an increasing RF voltage ramp for the mass-selective instability scan) is commonly used as an analytical scan for ion detection with quadrupole ion trap instruments. A number of phenomena have been observed while using this scan technique. These include space charge effects resulting in the delayed ejection of ions from the ion trap, and the fragmentation of fragile ions producing very broad peaks. Here the use of a reverse scan (i.e. a decreasing RF voltage ramp) is examined to determine the effect of the above phenomena in this acquisition method. With regard to space charge effects, the apparent reduction of the carbon isotope spacing below one Thomson (for singly charged ions) that is observed with the forward scan is now replaced by an apparent increase in this spacing. The reverse scan, which optimizes at lower axial modulation ejection voltages than the forward scan, allows for the intact ejection of fragile ions under its typical operating conditions whereas the forward scan results in fragmentation. Reducing the axial modulation voltage for the ejection of ions in the forward scan results in less dissociation of the fragile ions during ion ejection, but with the observation of ghost peaks due to incomplete ejection of all of the ions at the resonance ejection condition. While performing the reverse scan experiment, the formation of product ions from dissociation of the MH(+) ion has also been observed.     

Investigations into the production and interconversion of phomoidrides A-D

[structure: see text] Fermentation of ATCC 74256 led to the isolation and identification of C7 epimers of phomoidride A (CP-225,917) and phomoidride B (CP-263,114). We suggest the names phomoidrides C and D for these new fermentation products. Studies on the effect of pH on the distribution of phomoidrides A-D suggest phomoidride B (CP-263,114) is the first-formed secondary metabolite and the source of the remaining three phomoidrides.