Isolation and Crystal Structure of Novel by-products Observed During the Formation of bis(thiosemicarbazones)

During the condensation of 4-methyl-4-phenyl-3-thiosemicarbazide (3) with 2,3-butanedione an unexpected by-product, 8a-methyl-6,8a-dihydro-8-methyl-2-[N-methyl-N-phenylamino]-5H-1,3,4-thiadiazolo[3,2-d][1,2,4]triazine-5-thione, (5) was obtained in addition to the desired bis(thiosemicarbazone) (4). An X-ray crystal structure was obtained and is presented together with a proposed mechanism for its formation. A brief investigation of the coordination chemistry of bicycle (5) was carried out. The formation of cyclic compounds during the synthesis of analogues with extended backbones is also described.     

Sparsely substituted chlorins as core constructs in chlorophyll analogue chemistry. II. Derivatization

Stable chlorins bearing few or no substituents have been subjected to a variety of reactions including demetalation, magnesium insertion, oxochlorin formation, and bromination followed by Suzuki coupling. The kinetics of deuteration also have been determined for two oxochlorins and a series of chlorins bearing 0, 1, 2, or 3 meso-aryl substituents.     

Covalent and non-covalent albumin binding of Au(i) bis-NHCs via post-synthetic amide modification

Recent decades have witnessed the emergence of Au(i) bis-N-heterocyclic carbenes (NHCs) as potential anticancer agents. However, these systems exhibit little interaction with serum proteins (e.g., human serum albumin), which presumably impacts their pharmacokinetic profile and tumor exposure. Anticancer drugs bound to human serum albumin (HSA) often benefit from significant advantages, including longer circulatory half-lives, tumor targeted delivery, and easier administration relative to the drug alone. In this work, we present Au(i) bis-NHCs complexes, 7 and 9, capable of binding to HSA. Complex 7 contains a reactive maleimide moiety for covalent protein conjugation, whereas its congener 9 contains a naphthalimide fluorophore for non-covalent binding. A similar drug motif was used in both cases. Complexes 7 and 9 were prepared from a carboxylic acid functionalized Au(i) bis-NHC (complex 2) using a newly developed post-synthetic amide functionalization protocol that allows coupling to both aliphatic and aromatic amines. Analytical, and in vitro techniques were used to confirm protein binding, as well as cellular uptake and antiproliferative activity in A549 human lung cancer cells. The present findings highlight a hitherto unexplored approach to modifying Au(i) bis-NHC drug candidates for protein ligation and serve to showcase the relative benefits of covalent and non-covalent HSA binding.

Au(i) bis-N-heterocyclic carbenes (NHCs) functionalized using an amide linker were found to bind to human serum albumin (HSA) in covalent and non-covalent fashion. The solubility and in vitro anti-cancer activity of these new conjugates were studied.     

Forwards and backwards – synthesis of Laurencia natural products using a biomimetic and retrobiomimetic strategy incorporating structural reassignment of laurefurenynes C–F

Laurefurenynes C–F are four natural products isolated from Laurencia species whose structures were originally determined on the basis of extensive nuclear magnetic resonance experiments. On the basis of a proposed biogenesis, involving a tricyclic oxonium ion as a key intermediate, we have reassigned the structures of these four natural products and synthesized the four reassigned structures using a biomimetic approach demonstrating that they are the actual structures of the natural products. In addition, we have developed a synthesis of the enantiomers of the natural products laurencin and deacetyllaurencin from the enantiomer of (E)-laurefucin using an unusual retrobiomimetic strategy. All of these syntheses have been enabled by the use of tricyclic oxonium ions as pivotal synthetic intermediates.

The synthesis and structural reassignment of laurefurenynes C–F has been achieved, with the new structures fitting with a proposed biosynthesis. Also reported is the synthesis of ent-laurencin and ent-deacetyllaurencin via a retrobiomimetic approach.     

Simplified current decoupler for microchip capillary electrophoresis with electrochemical and pulsed amperometric detection

There is a need to develop broadly applicable, highly sensitive detection methods for microchip CE that do not require analyte derivatization. LIF is highly sensitive but typically requires analyte derivatization. Electrochemistry provides an alternative method for direct analyte detection; however, in its most common form, direct current (DC) amperometry, it is limited to a small number of easily oxidizable or reducible analytes. Pulsed amperometric detection (PAD) is an alternative waveform that can increase the number of electrochemically detectable analytes. Increasing sensitivity for electrochemical detection (EC) and PAD requires the isolation of detection current (nA) from the separation current (muA) in a process generally referred to as current decoupling. Here, we present the development of a simple integrated decoupler to improve sensitivity and its coupling with PAD. A Pd microwire is used as the cathode for decoupling and a second Au or Pt wire is used as the working electrode for either EC or PAD. The electrode system is easy to make, requiring no clean-room facilities or specialized metallization systems. Sensitive detection of a wide range of analytes is shown to be possible using this system. Using this system we were able to achieve detection limits as low as 5 nM for dopamine, 74 nM for glutathione, and 100 nM for glucose.     

Studies in qualitative inorganic analysis. Part XXVIII

Summary Schemes for the analysis of the Copper-Tin group are reviewed. The advantages of the scheme recommended by the Midlands Association for Qualitative Analysis are discussed.

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Zusammenfassung Analysen-Schemata für die Kupfer-Zinn-Gruppe wurden besprochen. Die Vorteile des Analysenganges der Midlands Association for Qualitative Analysis werden diskutiert.

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Résumé Examen des différents processus d'analyse du groupe cuivre-étain. Discussion des avantages de la technique recommandée par la Midlands. Association pour l'analyse qualitative.

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Part XXVII: Mikrochim. Acta [Wien]1967, 389.     

Existence theorem for solitary waves on lattices

In this article we give an existence theorem for localized travelling wave solutions on one-dimensional lattices with Hamiltonian $$H = \sum\limits_{n \in \mathbb{Z}} {\left( {\tfrac{1}{2}p_n^2 + V(q_{n + 1} - q_n )} \right)} ,$$ whereV(·) is the potential energy due to nearest-neighbour interactions. Until now, apart from rare integrable lattices like the Toda latticeV(φ)=ab ^?1(e ^?bφ+bφ?1), the only evidence for existence of such solutions has been numerical. Our result in particular recovers existence of solitary waves in the Toda lattice, establishes for the first time existence of solitary waves in the (nonintegrable) cubic and quartic latticesV(φ)= 1/2φ ² + 1/3aφ ³,V(φ) = 1/2φ ² + 1/4bφ ⁴, thereby confirming the numerical findings in [1] and shedding new light on the recurrence phenomena in these systems observed first by Fermi, Pasta and Ulam [2], and shows that contrary to widespread belief, the presence of exact solitary waves is not a peculiarity of integrable systems, but “generic” in this class of nonlinear lattices. The approach presented here is new and quite general, and should also be applicable to other forms of lattice equations: the travelling waves are sought as minimisers of a naturally associated variational problem (obtained via Hamilton's principle), and existence of minimisers is then established using modern methods in the calculus of variations (the concentration-compactness principle of P.-L. Lions [3]).