Zapotin, a Polymethoxyflavone, with Potential Therapeutic Attributes

The use of plants as traditional medicines is common and has prevailed in many different cultures over time. Polymethoxyflavones (PMFs) are natural polyphenols from the group of flavonoids. Zapotin, a member of the PMFs, is found mainly in citrus plants and is almost exclusively limited to their peels. The chemical structure of zapotin has been questioned from the very beginning, since the structure of flavonoids with a single oxygen atom in the C2′ position is extremely rare in the plant kingdom. To clarify this, the structural determination and bio-inspired synthesis of zapotin are discussed in detail in this review. Due to the broad biological potential of PMFs, the complication in the isolation process and characterization of PMFs, as well as their purification, have been estimated by adapting various chromatographic methods. According to available data from the literature, zapotin may be a promising curative agent with extensive biological activities, especially as a chemopreventive factor. Apart from that, zapotin acts as an antidepressant-like, anticancer, antifungal, and antioxidant agent. Finally, accessible studies about zapotin metabolism (absorption, distribution, metabolism, excretion, and toxicity) underline its potential in use as a therapeutic substance.

Chemical genetics strategy to profile kinase target engagement reveals role of FES in neutrophil phagocytosis via SYK activation

Chemical tools and methods that report on target engagement of endogenously expressed protein kinases by small molecules in human cells are highly desirable. Here, we describe a chemical genetics strategy that allows the study of non-receptor tyrosine kinase FES, a promising therapeutic target for cancer and immune disorders. Precise gene editing was used in combination with a rationally designed, complementary fluorescent probe to visualize endogenous FES kinase in HL-60 cells. We replaced a single oxygen atom by a sulphur in a serine residue at the DFG-1 position of the ATP-binding pocket in an endogenously expressed kinase, thereby sensitizing the engineered protein towards covalent labeling and inactivation by a fluorescent probe. The temporal control offered by this strategy allows acute inactivation of FES activity both during myeloid differentiation and in terminally differentiated neutrophils. Our results show that FES activity is dispensable for differentiation of HL-60 cells towards macrophages. Instead, FES plays a key role in neutrophil phagocytosis by activation of SYK kinase, a central regulator of immune function in neutrophils. This strategy holds promise as a target validation method for kinases.

Geometric and electronic properties of gold clusters doped with a single oxygen atom

A systematic theoretical study on single oxygen atom doped gold clusters showed that a single oxygen atom can be adsorbed on various sites of gold surfaces, and obtain nearly one electron from gold atoms.

Single and double addition of oxygen atoms to propyne on surfaces at low temperatures

Experiments designed to simulate the low temperature surface chemistry occurring in interstellar clouds provide clear evidence of a reaction between oxygen atoms and propyne ice. The reactants are dosed onto a surface held at a fixed temperature between 14 and 100 K. After the dosing period, temperature programmed desorption (TPD), coupled with time-of-flight mass spectrometry, are used to identify two reaction products with molecular formulae C3H4O and C3H4O2. These products result from the addition of a single oxygen atom, or two oxygen atoms, to a propyne reactant. A simple model has been used to extract kinetic data from the measured yield of the single-addition (C3H4O) product at surface temperatures from 30–100 K. This modelling reveals that the barrier of the solid-state reaction between propyne and a single oxygen atom (160 ± 10 K) is an order of magnitude less than that reported for the gas-phase reaction. In addition, estimates for the desorption energy of propyne and reaction rate coefficient, as a function of temperature, are determined for the single addition process from the modelling. The yield of the single addition product falls as the surface temperature decreases from 50 K to 30K, but rises again as the surface temperature falls below 30 K. This increase in the rate of reaction at low surface temperatures is indicative of an alternative, perhaps barrierless, pathway to the single addition product which is only important at low surface temperatures. The kinetic model has been further developed to characterize the double addition reaction, which appears to involve the addition of a second oxygen atom to C3H4O. This modelling indicates that this second addition is a barrierless process. The kinetic parameters we extract from our experiments indicate that the reaction between atomic oxygen and propyne could occur under on interstellar dust grains on an astrophysical time scale.

A Preliminary Remark: Water and Friends

Water is the most miraculous of fluids. As well as being ubiquitous on Earth and essential for life as we know it, it has remarkable properties which at first sight don’t seem to be consistent with its almost laughably simple chemical composition. Each molecule of water consists of a single oxygen atom (O) and two hydrogen atoms (H); its chemical formula is therefore, as just about everyone already knows, H2O. Here is one odd but hugely important anomalous property. A water molecule is only slightly heavier than a methane molecule (CH4; C denotes a carbon atom) and an ammonia molecule (NH3, N denotes a nitrogen atom). However, whereas methane and ammonia are gases, water is a liquid at room temperature. Water is also nearly unique in so far as its solid form, ice, is less dense than its liquid form, so ice floats on water. Icebergs float in water; methanebergs and ammoniabergs would both sink in their respective liquids in an extraterrestrial alien world, rendering their Titanics but not their Nautiluses safer than ours. Another very important property is that water is an excellent solvent, being able to dissolve gases and many solids. One consequence of this ability is that water is a common medium for chemical reactions. Once substances are dissolved in it, their molecules can move reasonably freely, meet other dissolved substances, and react with them. As a result, water will figure large in this book and this preliminary comment is important for understanding what is to come. You need to get to know the H2O molecule intimately, for from it spring all the properties that make water so miraculous and, more prosaically, so useful. The molecule also figures frequently in the illustrations, usually looking like 1, where the red sphere denotes an O atom and the pale grey spheres represent H atoms. Actual molecules are not coloured and are not made up of discrete spheres; maybe 2 is a better depiction, but it is less informative. I shall use the latter representation only when I want to draw your attention to the way that electrons spread over the atoms and bind them together.