On the Mechanism of Thiamine Action. IV.1 Evidence from Studies on Model Systems

Molecular imprinting science and technology: a survey of the literature for the years up to and including 2003

Fluorescence spectroscopy, one of the most informative and sensitive analytical techniques, has played and continues to play key roles in modern research. Indeed, unraveling the inner workings of biomolecules, cells and organisms relied on the development of fluorescence-based tools. As many of the players in these sophisticated interactions and exceedingly complex systems are not inherently emissive, researchers have relied on synthesizing fluorescent analogs of the building blocks found in biological macromolecules. These are the constituents of the cell surface and cell membrane, as well as proteins and nucleic acids. This review article is dedicated to emissive analogs of these relatively small molecules.

For organizational purposes, we have arbitrarily selected to approach these diverse families of biomolecules by imagining “a journey into the center of the cell”. Approaching the exterior of a cell, one first encounters oligosaccharides that decorate the cell surface and are involved in cell recognition and signaling. Next, we arrive at the cell membrane itself. This semi-permeable envelope sets the cell boundaries and regulates its traffic. Several types of building blocks assemble this membrane, most notably among them are the phospholipids. Upon entering the cell, the cytosol reveals a plethora of small and large molecules, including proteins, as well as soluble RNA molecules and RNA-rich ribosomes. Within the cytosol of eukaryotes and prokaryotes lies the nucleus or nucleoid, respectively. This membrane-enclosed control center contains most of the cells’ genetic material. DNA, the cellular blueprint, is permanently found in the nucleus, which also hosts diverse RNA molecules. Accordingly, we first discuss emissive carbohydrate derivatives. We then present fluorescent membrane constituents, followed by emissive amino acids. Our journey ends by focusing on emissive analogs of nucleosides and nucleotides, the building blocks of nucleic acids.

The common biomolecular building blocks, excluding a few amino acids, lack appreciably useful fluorescence properties. This implies that structural modifications are required to impart such photophysical features. Ideally, a designer probe should closely resemble its natural counterpart in size and shape without the loss of the original function (a feature we refer to as “isomorphicity”). This presents a fundamental predicament, as any modification attempting to alter the electronic nature of a molecule, typically by including aromatic residues or extending conjugation, will also alter its steric bulk and therefore the interactions with its surroundings.

Clearly not all biomolecular building blocks can or need to accommodate strict isomorphic design criteria. The heterocycles found in nucleosides already provide a platform that facilitates the extension of π-conjugation, which is also true for some aromatic amino acids. In contrast, employing fluorescence spectroscopy to membrane research requires very creative probe designs. Saccharides can be viewed as the most restrictive in this context, as no chemical modification is conceivable without a major structural disruption and likely loss of function. Such aliphatic biomolecules accommodate labeling only, where an established fluorophore is covalently conjugated to provide an emissive derivative. We therefore reserve the term probe to molecular designs that are expected to furnish useful modified biomolecules capable of reliable reporting. Understandably, fluorescent probes must meet the most stringent isomorphic design principles to ensure a biologically meaningful read-out. The isomorphic design principle is therefore a central theme of this review.

This article focuses on designing fluorescent probes for the four major families of macromolecular building blocks discussed above. Although not necessarily in chronological order, it spans roughly four decades of probe design with emphasis, when justified, on recent contributions. As the reader may imagine, this topic encapsulates a vast research field and cannot be comprehensively reviewed within the space limitation of Chemical Reviews. Nevertheless, we have attempted to summarize the most important and general contributions discussing fluorescent probes that were designed to shed light on biological processes and refer the reader to other resources.1 Although a few examples have found their way into the text, we do not generally address here the development of small molecule fluorophores and sensors that are not part of biomolecular assemblies. We open this article with a brief overview of the key features of fluorescence spectroscopy, where essential theoretical, experimental, and practical elements are discussed.

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Fluorescent Analogs of Biomolecular Building Blocks: Design, Properties, and Applications

A Roadmap to the Ammonia Economy

An efficient, copper-based catalyst has been discovered that oxidizes a wide range of alcohols into aldehydes and ketones under mild conditions. This catalytic system utilizes oxygen or air as the ultimate, stoichiometric oxidant, producing water as the only by-product.

https://science.sciencemag.org/content/sci/274/5295/2044.full.pdf

Copper-Catalyzed Oxidation of Alcohols to Aldehydes and Ketones: An Efficient, Aerobic Alternative

In aqueous solutions of ATP-complexes of some bivalent alkaline earth and 3d transition metal ions the degree of co-ordination between metal ion and adenine ring has been estimated from UV. Difference spectra. In Ca-ATP, Mg-ATP, Mn-ATP, Co-ATP, Ni-ATP and Zn-ATP only a low percentage of the complex molecules show co-ordination between metal ion and adenine ring, whereas in Cu-ATP complex particles with metal-adenine co-ordination predominate.

Zur Struktur der ATP.‐Komplexe zweiwertiger Kationen IV. Koordinative Besetzung des Adeninrings

Eine Reihe von Verbindungen, die fahig sind, Metalle komplex zu binden, wird auf ihre tuberkulostatische Wirkung untersucht. Es zeigt sich, dass bei einigen in vitro und beim 5-Oxychinoxalin auch in vivo durch Cu‥ eine. Steigerung der Aktivitat zu erzielen ist.

Über die Beeinflussung tuberkulostatischer Wirkungen durch Cu‥. Metallionen und biologische Wirkung, 7. Mitteilung

The hitherto unknown compounds 2-(2′-thieny1)-pyridine and methyl α-picolyl sulphide have been synthesized. The stability constants of Ni2+, Cu2+ and Zn2+ complexes with these two substances and with pyridine, α-picoline, β-picoline, γ-picoline, and 2-phenylpyridine have been measured and are discussed. Evidence for the coordination of the sulphur atom in methyl α-picolyl sulphide as well as in the aromatic 2-(2′-thieny1)-pyridine is given. It is also shown that thiophene is able to coordinate to Cu2+.

Schwefel in aromatischen Verbindungen als Ligandatom in Chelatkomplexen II

The 8-methyl group of riboflavin and lumiflavin is shown to be activated, in agreement with B. & A. Pullman's LCAO-MO-model. Chemical evidence for this is given by reactions of 8-chloro-7,10-dimethyl-flavin with nucleophilic agents, of 8-methylflavins with NO and CO groups, and by the base-catalysed dimerisation of 8-methylflavins giving rise to a new class of flavin-like pigments. The particular redox-behaviour of these “biflavins” is described and their possible biochemical importance is discussed.

Studien in der Lumiflavin‐Reihe V. Spezifische Reaktivität 8‐ständiger Substituenten am Isoalloxazin‐Kern Flavin‐Dimere

The complex alkylation reactions of leucoflavin derivatives are shown to give O-substituted products of a new type rather than N-substituted ones. Characteristic differences in the chemical behaviour of (iso)alloxazines and of their leuco-compounds are outlined. Stabilization and decomposition of flavosemiquinones have been further studied. It is shown, that flavin catabolism (N-10-dealkylation) occurs in the semiquinonoid state at room temperature, and is neither confined to hydroxyalkylflavins, nor to specific catalysis by light. Based upon these and recent findings of other authors, a new mechanism of metal-catalysed flavin catabolism is proposed. 1,3,10-Trimethyl-leucoflavin was prepared and found to give a stabilized monomeric semiquinone on oxidation.

H. Erlenmeyer

Papers

Zur Struktur der ATP.‐Komplexe zweiwertiger Kationen IV. Koordinative Besetzung des Adeninrings

Über die Beeinflussung tuberkulostatischer Wirkungen durch Cu‥. Metallionen und biologische Wirkung, 7. Mitteilung

Schwefel in aromatischen Verbindungen als Ligandatom in Chelatkomplexen II

Studien in der Lumiflavin‐Reihe V. Spezifische Reaktivität 8‐ständiger Substituenten am Isoalloxazin‐Kern Flavin‐Dimere

Studien in der Lumiflavin‐Reihe VI. Alkylierungs‐ und Desalkylierungs‐Reaktionen an (Iso)alloxazinen; 1,3,10‐Trimethylflavosemichinone