Carbon Dioxide Utilisation -The Formate Route

UIDB/50006/2020 CEEC-Individual 2017 Program Contract.The relentless rise of atmospheric CO2 is causing large and unpredictable impacts on the Earth climate, due to the CO2 significant greenhouse effect, besides being responsible for the ocean acidification, with consequent huge impacts in our daily lives and in all forms of life. To stop spiral of destruction, we must actively reduce the CO2 emissions and develop new and more efficient “CO2 sinks”. We should be focused on the opportunities provided by exploiting this novel and huge carbon feedstock to produce de novo fuels and added-value compounds. The conversion of CO2 into formate offers key advantages for carbon recycling, and formate dehydrogenase (FDH) enzymes are at the centre of intense research, due to the “green” advantages the bioconversion can offer, namely substrate and product selectivity and specificity, in reactions run at ambient temperature and pressure and neutral pH. In this chapter, we describe the remarkable recent progress towards efficient and selective FDH-catalysed CO2 reduction to formate. We focus on the enzymes, discussing their structure and mechanism of action. Selected promising studies and successful proof of concepts of FDH-dependent CO2 reduction to formate and beyond are discussed, to highlight the power of FDHs and the challenges this CO2 bioconversion still faces.publishersversionpublishe

Liposomal formulation of a methotrexate lipophilic prodrug: assessment in tumor cells and mouse T-cell leukemic lymphoma

Anna A Alekseeva,1 Ekaterina V Moiseeva,1 Natalia R Onishchenko,1 Ivan A Boldyrev,1 Alexander S Singin,2,† Andrey P Budko,2 Zoya S Shprakh,2 Julian G Molotkovsky,1 Elena L Vodovozova1 1M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, 2N.N. Blokhin Russian Cancer Research Center, the Ministry of Health of the Russian Federation, Moscow, Russian Federation †Alexander S Singin passed away on October 4, 2011 Abstract: In a previous study, a formulation of methotrexate (MTX) incorporated in the lipid bilayer of 100-nm liposomes in the form of diglyceride ester (MTX-DG, lipophilic prodrug) was developed. In this study, first, the interactions of MTX-DG liposomes with various human and mouse tumor cell lines were studied using fluorescence techniques. The liposomes composed of egg phosphatidylcholine (PC)/yeast phosphatidylinositol/MTX-DG, 8:1:1 by mol, were labeled with fluorescent analogs of PC and MTX-DG. Carcinoma cells accumulated 5 times more MTX-DG liposomes than the empty liposomes. Studies on inhibitors of liposome uptake and processing by cells demonstrated that the formulation used multiple mechanisms to deliver the prodrug inside the cell. According to the data from the present study, undamaged liposomes fuse with the cell membrane only 1.5–2 hours after binding to the cell surface, and then, the components of liposomal bilayer enter the cell separately. The study on the time course of plasma concentration in mice showed that the area under the curve of MTX generated upon intravenous injection of MTX-DG liposomes exceeded that of intact MTX 2.5-fold. These data suggested the advantage of using liposomal formulation to treat systemic manifestation of hematological malignancies. Indeed, the administration of MTX-DG liposomes to recipient mice bearing T-cell leukemic lymphoma using a dose-sparing regimen resulted in lower toxicity and retarded lymphoma growth rate as compared with MTX. Keywords: liposomes, methotrexate, lipophilic prodrug, endocytosis, hematological malignancies, leukemia/lymphom

A space between two worlds: St. Petersburg in the early eighteenth century

In May 1703, Tsar Peter I of Russia is alleged to have led a small military foray to the Baltic coastline, near the mouth of the river Neva. Accounts of this occasion, both contemporary and retrospective, vary considerably on the precise chronology of the decision-making process and the question of whether the tsar himself was actually present. Regardless of the precise details, the area was claimed (or, some argue, reclaimed) in the name of Russia and plans were made to build a fortress in order to consolidate the Russian presence. This foundation and the associated myths, which have been explored by many writers and historians over the intervening centuries, feature in most discussions of St. Petersburg’s history. One such myth, which presents Peter creating his new city out of nothing, in a wilderness, was essentially poetic license on the part of later writers such as Vasilii Trediakovskii and Aleksandr Pushkin. In fact, the area was the site of a Swedish fortress known as “Nienschants,” the town of Nien, with a population of around four thousand, and a number of smaller settlements nearby that existed before the city was founded. Indeed, given the paucity of usable stone in the region, the ruins of the old fortress likely provided material used in the initial stage of St. Petersburg’s construction, particularly in the foundations of buildings