Functionalized hyperbranched polymers via olefin metathesis

Hyperbranched polymers are highly branched, three-dimensional macromolecules which are closely related to dendrimers and are typically prepared via a one-pot polycondensation of AB_(n≥2) monomers.^1 Although hyperbranched macromolecules lack the uniformity of monodisperse dendrimers, they still possess many attractive dendritic features such as good solubility, low solution viscosity, globular structure, and multiple end groups.^1-3 Furthermore, the usually inexpensive, one-pot synthesis of these polymers makes them particularly desirable candidates for bulk-material and specialty applications. Toward this end, hyperbranched polymers have been investigated as both rheology-modifying additives to conventional polymers and as substrate-carrying supports or multifunctional macroinitiators, where a large number of functional sites within a compact space becomes beneficial

Formation and modern state of ecosystem in Tolmachevskoye reservoir (Kamchatka) and the acclimatized there population of kokanee ( <i>Oncorhynchus nerka kennerlyi</i>)

Evolution of local ecosystem in Tolmachevskoye reservoir and changes in its artificial population of kokanee salmon are traced on the data of authors’ observations in 2009-2013 and previous archival and cited data. Decreasing of inorganic phosphorous, nitrogen, and bioavailable iron is detected in the water against a background of water warming. As the result, phytoplankton production and abundance decrease, its species composition becomes simpler, chlorophyll а concentration becomes lower. Zooplankton abundance is stable (1-2 g/m3), as before the reservoir appearance, but species structure of plankton crustaceans is changed, and the copepods Cyclops scutifer , small cladocerans Holopedium gibberum, Bosmina longirostris , and Daphnia ( Daphnia ) cristata group prevail recently. The salmon food spectrum is wide and includes a lot of unedible fractions as wood chips and plant detritus; coefficient of consumption is high - these factors indicate a deficiency of forage resources for fish. The fish condition indicates a chronic malnutrition. The state of female gonads is satisfactory, without any visible pathology, as in 2003-2007, but the oocytes resorption goes concurrently with maturation of gonads that is a sign of hard competition for the food within the kokanee population. The current stable state of the population differs from preceded stages of its development by lower stock add smaller size of fish, the age of spawning is now 4-7 years. Among other freshwater fish, the kokanee salmon is distinguished by high content of ω-3 polyunsaturated fatty acids. Artificial populations in Kamchatka could be considered as a resource for both amateur or sport fishing and commercial aquaculture

Organometallic palladium reagents for cysteine bioconjugation

Reactions based on transition metals have found wide use in organic synthesis, in particular for the functionalization of small molecules. However, there are very few reports of using transition-metal-based reactions to modify complex biomolecules, which is due to the need for stringent reaction conditions (for example, aqueous media, low temperature and mild pH) and the existence of multiple reactive functional groups found in biomolecules. Here we report that palladium(II) complexes can be used for efficient and highly selective cysteine conjugation (bioconjugation) reactions that are rapid and robust under a range of bio-compatible reaction conditions. The straightforward synthesis of the palladium reagents from diverse and easily accessible aryl halide and trifluoromethanesulfonate precursors makes the method highly practical, providing access to a large structural space for protein modification. The resulting aryl bioconjugates are stable towards acids, bases, oxidants and external thiol nucleophiles. The broad utility of the bioconjugation platform was further corroborated by the synthesis of new classes of stapled peptides and antibody–drug conjugates. These palladium complexes show potential as benchtop reagents for diverse bioconjugation applications.National Institutes of Health (U.S.) (GM-58160)National Institutes of Health (U.S.) (GM-101762)MIT Faculty Start-up FundDamon Runyon Cancer Research FoundationSontag Foundation (Distinguished Scientist Award)Massachusetts Institute of Technology. Dept. of Chemistry (George Buchi Research Fellowship)David H. Koch Institute for Integrative Cancer Research at MIT (Graduate Fellowship in Cancer Research

Development of new catalytic transformations and reagents for the construction of C-N and C-S bonds

Thesis: Ph. D. in Organic Chemistry, Massachusetts Institute of Technology, Department of Chemistry, 2015.Cataloged from PDF version of thesis. Vita.Includes bibliographical references.Chapter 1. Palladium-Catalyzed Cross-Coupling of Aryl Chlorides and Triflates with Sodium Cyanate: A Practical Synthesis of Unsymmetrical Ureas. An efficient method for palladium-catalyzed cross-coupling of aryl chlorides and triflates with sodium cyanate is reported. The protocol allows for the synthesis of unsymmetrical N,N'-di- and N,N,N'-trisubstituted ureas in one pot, and is tolerant of a wide range of functional groups. Insight into the mechanism of aryl isocyanate formation is gleaned through studies of the transmetallation and reductive elimination steps of the reaction, including the first demonstration of reductive elimination from an arylpalladium isocyanate complex to produce an aryl isocyanate. Chapter 2. Palladium-Catalyzed Synthesis of N-Aryl Carbamates. An efficient synthesis of aryl carbamates was achieved by performing palladiumcatalyzed cross-coupling of ArX (X = CI, OTf) with sodium cyanate in the presence of alcohols. The use of aryl triflates as electrophilic components in this transformation allowed for an expanded substrate scope for the direct synthesis of aryl isocyanates. This methodology provides direct access to major carbamate protecting groups, Sthiocarbamates, and diisocyanates, which are precursors to polyurethane materials. Chapter 3. Structural Reevaluation of the Electrophilic Hypervalent Iodine Reagent for Trifluoromethylthiolation. Hypervalent iodine [lambda]3-benziodoxoles are common electrophilic transfer reagents known for their enhanced stability compared to their non-cyclic analogues. Here we present data showing that chlorobenziodoxole reacts with two different thiolate nucleophiles (thiocyanate and trifluoromethylthiolate) resulting in the formation of stable thioperoxy complexes rather than the expected benziodoxole derivatives. We further report a revised structure for the earlier described electrophilic trifluoromethylthiolation reagent (1), previously believed to contain the benziodoxole framework. Our findings, which are based on a combination of analytical techniques, including the recently introduced crystalline sponge method for X-ray analysis, unambiguously demonstrate that 1 is a thioperoxy compound both in solution and the solid state. Chapter 4. Organometallic Palladium Reagents for Cysteine Bioconjugation. Organometallic palladium reagents for the selective S-arylation of biomolecules are described. This new bioconjugation toolkit provides a highly versatile technique for the fast functionalization of cysteine with aromatic scaffolds under a broad range of reaction conditions (e.g., pH, solvent, temperature). The resulting bioconjugates are stable under basic and acidic conditions, as well as in the presence of external thiol nucleophiles. The substitution pattern on the aryl ring can be varied to achieve high levels of stability toward oxidation. Lastly, new types of bio-therapeutics - stapled peptides and linker-free antibody-drug conjugates - could be synthesized using the new method.by Ekaterina V. Vinogradova.Ph. D. in Organic Chemistr

Stress and neurobiology of coping styles

In stressful environment, animal can use different coping strategies. Passive animals manifest freezing behaviour at predator attacks, active ones are trying to have an impact on a stressful situation. Each coping style is presupposed to have a neurobiological basis and it helps animals to survive in aggressive and mutable environment. Being under a long lasting stress, leaders can be affected by cardiovascular and ulcer diseases, but a short term impact can cheer them up, improve neuroendocrine stress response more than passive coping style in animals. This paper analyzes animal pattern of coping behaviour, their inheritance based on gender, social status and age. The research shows how anxiety affects social behaviour of people individuals and typological reactions were compared. These patterns can be used by people in a situation of uncontrolled stress to prevent diseases and depressive disorders through altering one’s type of behavior to the one which is more effective. In addition, knowledge of behavioural types can assist teachers in implementing the learning process as in stress situations (e.g. taking exams, working on course papers, doing tests) not all students are able to effectively perceive and present the resulting material. On the other hand, active students could encourage short-term rather than long-term stressor irritation. It is necessary to pay special attention to students with low social economic status who display active response to stress. According to statistics, problem students often become aggressors and commit antisocial and sometimes criminal acts. The coping styles mentioned here above are not polar, there are no clear boundaries of personality. In addition, behaving according to the active / non-active type is identified by customary and inherited behaviour patterns

Multiplexed proteomic profiling of cysteine reactivity and ligandability in human T cells

Summary: Differential amino acid reactivity with chemical probes can provide valuable information on the functionality and ligandability of proteins in native biological systems. Here, we present a quantitative, multiplexed chemical proteomic protocol for in-depth reactivity and ligandability profiling of cysteines in proteins in quiescent and stimulated T cells. This protocol illuminates dynamic immune state-dependent alterations in cysteine reactivity, revealing chemoselective and stereoselective small-molecule interactions with cysteines in structurally and functionally diverse proteins that lack chemical probes.For complete details on the use and execution of this protocol, please refer to Vinogradova et al. (2020)

Leaf Extracts of Invasive Woody Species Demonstrate Allelopathic Effects on the Growth of a Lawn Grass Mixture

Biochemical composition was studied in the leaf litter of alien woody species included in the 100 most aggressive invasive species of Europe: Ailanthus altissima, Quercus rubra, Acer negundo, Robinia pseudoacacia, and Elaeagnus angustifolia. Using GC-MS, we detected 187 metabolites in the leaf litter, which are phenolic acids and their derivatives, carbohydrates and their derivatives, polyphenolic compounds, cyclic esters, glycosides, and amino acids and their derivatives. Species-specific metabolites were identified for each species. The main allelochemicals in the leaf litter extract of Q. rubra are determined mainly by the relative abundance of phenolic and fatty acids and their esters, whereas those in the leaf litter extract of R. pseudoacacia are determined by carbohydrates and their derivatives and ester of fatty acid, and those in the leaf litter extract of A. altissima are determined by glycosides. Profiles of macro- and microelements were characterized. It was found that aqueous extracts of leaf litter from all the invasive woody plants under study have a negative effect on the seed germination and initial growth of Vicia cracca and Avena strigosa used for the reclamation of disturbed urban and industrial lands. At the same time, V. cracca is potentially more sensitive