Parte 1
12
0
0
Texto completo
(2) The fascinating forms of carbon… Carbon nanoonions. Nanohorns. Peapods. C60@C240@C540. 5 nm. J. Mater. Chem. 2008, 18, 1415-1592 Special issue on Carbon Nanostructures. The fascinating forms of carbon…. Nanocups. Nanotorus. Nanobuds J. Mater. Chem. 2008, 18, 1415-1592 Special issue on Carbon Nanostructures.
(3) Fullerenos para aplicaciones biológicas. Content: • • • • •. Introduction (short) to the use of Fullerenes for biological applications Carbohydrate-protein interactions Synthesis of [60]Fullerene derivatives as “multivalent” Scaffold Glycofullerenes as new and potent inhibitors of viral Infection Other carbon nanoforms (SWCNT and SWCNH) as “multivalent” scaffolds. Biological Applications of Fullerenes?. C60 in toluene. • Fullerene C60 is a toxic molecule which is insoluble in water!!!.
(4) Biological Applications of Fullerenes?. • Fullerenes in contact with water form toxic colloidal aggregates (nC60).. • Clusters of C60 can cause oxidative damage to lipids in the brains of fish. • C60 is highly hydrofobic and redox active, therefore, it can potentially cause oxidative damage. Water dispersed C60 provokes oxidative stress in the brain of largemouth bass and depletion of glutathione in the gills of fish. • This in vivo study, showing the adverse effect of C60 in aquatic species, may predict potential effects in humans.. Biological Applications of Fullerenes?. • Fullerene C60 is a toxic molecule which is insoluble in water!!!. • Therefore, different strategies have been explored to render fullerenes biocompatible. • Solubilization and chemical functionalization are the starting point to integrate this material into living systems (aminoacids, sugars, cyclodextrins, etc).
(5) Biological Applications of Fullerenes? Suitably functionalized, fullerenes show interesting biological properties Anticancer and Inmunological properties. Fullerenes as antiviruses. Photodynamic Therapy. Neuroprotection and antioxidants. Fullerenes for drug delivery. Fullerenes for MRI. Fullerenos para aplicaciones biológicas. Content: • • • • •. Introduction (short) to the use of Fullerenes for biological applications Carbohydrate-protein interactions Synthesis of [60]Fullerene derivatives as “multivalent” Scaffold Glycofullerenes as new and potent inhibitors of viral Infection Other carbon nanoforms (SWCNT and SWCNH) as “multivalent” scaffolds.
(6) Carbohydrate Interactions. Glycocalyx • Protection • Social Behaviour TEM mammalian cell. Funtions of glycocalyx: • Protection: Cushions the plasma membrane and protects it from chemical injury. • Immunity to infection: Enables the immune system to recognize and selectively attack foreign organisms. • Defense against cancer: Changes in the glycocalyx of cancerous cells enable the immune system to recognize and destroy them. • Transplant compatibility: Forms the basis for compatibility of blood transfusions, and organ transplants. • Adhesion: Binds cells together so that tissues do not fall apart • Inflammation regulation: Glycocalyx coating on endothelial walls in blood vessels revents leukocytes from rolling/binding in healthy states. • Fertilization: Enables sperm to recognize and bind to eggs. • Embryonic development: Guides embryonic cells to their destinations in the body.. Carbohydrate Interactions. Glycocalyx • Protection • Social Behaviour TEM. cell. Carbohydrate-protein Interactions Highly selective Calcium dependent Low affinity Multivalent interaction.
(7) Multivalence MULTIVALENT SYSTEMS AND INTERACTION WITH THE GLYCOME. a) b) c). 5. d). Bardane fruits and VelcroTM A virus connecting to many celular receptors Linkage in the presence of a monovalent inhibitor (farmacological classical approach) Inhibiting the linkage and infection by using a multivalent inhibitor. R. Haag et al. Angew. Chem. Int. Ed. 2012, 51, 10472.. Biological examples (natural and pathogenic processes) Embryogenesis Fertilization. The development of tools to understand and intervene in these processes is a hot topic and must be based on a multivalent presentation of carbohydrates Metastases. Pathogen infection.
(8) O. O. O O. O. O. O. O. O. O. O. O. O. O. O. O. O. O. O. O. O. O. O. O. O. O. O. O. Glycopetides and Glycoproteins. O. O. O. O. O. O. O. O. n. Glycocyclodextrines and glycocalixarenes. Glycopolymers. O. O. O. O O. O. O. O O. O. O. O. O. O O S. O. S. O. S. S. O. S. O. S O. O. S S. S. S. S. O. O O. O. S S. O. O. S. S S. O. O. S. S. O. O. O. S. S. O. O. O. O. O. O. S. S. S. O. O. O O. O. O. O. O O O O. O. O O. O. O. O. O. O. O. O. O. Glycoliposomes. Glycodendrimers. Glyconanoparticles. Goals SYNTHESIS OF NEW WATER SOLUBLE C60 DERIVATIVES (biocompativility and toxicity effects. Globular shape and size control) Hexaaducts of [60]fullerene funcionalized with carbohydrates. Validation of fullerenes and other carbon nanoforms as an efficient and versatile scaffold for the multivalent presentation5 of carbohydrates!!!. Synthetic approach based on Bingel reaction and further 1,3-dipolar cycloadditions between alkynes and azides catalyzed by Cu(I) (CuAAC)..
(9) Synthesis CHEMICAL MODIFICATION OF FULLERENES: Toward water soluble fullerenes Optimizing the CuAAC reaction Reaction conditions: Catalyst: CuBr·S(CH3)2/ Cu0 Solvent: DMSO Reductant: Sodium ascorbate. Synthesis SYNTHESIS AND CHARACTERIZATION OF C60 HEXAADUCTS. Chem. Eur. J. 2011, 17, 766..
(10) Synthesis SYNTHESIS AND CHARACTERIZATION OF C60 HEXAADUCTS. 24H. MS: m/z= 2124.8. 1H-NMR. (700 MHz, CDCl3, 298 K) of alkyne-substituted hexaadduct showing its 84 protons. Synthesis SYNTHESIS AND CHARACTERIZATION OF C60 HEXAADUCTS. FTIR: 2100 cm-1 MS: m/z= 2124.8. 13C-NMR. (175 MHz, CDCl3, 298 K) of alkyne substituted hexaadduct (only 2 sp2 carbons of fullerene!!!).
(11) Synthesis SYNTHESIS AND CHARACTERIZATION OF C60 HEXAADUCTS. Sodium ascorbate. QuadraSil (Si/mercaptopropyl). (8-14) 1 8. 3 10. 2 9. 5 12 7 14. 4 11. 6 13. Synthesis SYNTHESIS AND CHARACTERIZATION OF C60 HEXAADUCTS. 8. 13C-NMR. spectrum (175 MHz, DMSO-d6, 298 K) of compound 8 Chem. Commun. 2010, 46, 3860..
(12) Properties Interaction between lectines and glycofullerenes. •. Excellent multivalent ligand. •. Validation of fullerenes as efficient plataform for the multivalent presentation of carbohydrates. 8. •. Increased valence in carbohydrates, but poorer interaction with Con A. •. Possible steric congestion and self-association phenomena. 12 Chem. Eur. J. 2011, 17, 766.. Diferent Molecular Sructures. ¡¡36 CARBOHYDRATES PER MOLECULE!!. We increase the number of carbohydrates per molecule as well as the spacer length…. Biomacromolecules 2013, 14 , 431..
(13)
Documento similar
The Commission notes the applicant's conviction for having edited, published and distributed various articles and finds, therefore, that there has been an interference with
1.3.2 Synthetic methodologies based on multicomponent reactions As the present thesis deals with multicomponent reaction for the synthesis of pyridine derivatives, we
a) Structural modifications of the chromenopyrazole scaffold led to the synthesis of new cannabinoids allowing fine-tuning of cannabinoid receptor affinity and
This manuscript undertakes a review of the effects resulting from the intake of proteins and/or amino acids administered in carbohydrate drinks as well as whey protein and
Some common approaches to the prediction of protein-protein interactions include: (i) transferring interactions between protein orthologs of different species (referred
Highest ef ficiencies for CZTS cells reported up to this date have been deposited via a process first reported by Shin et al in 2013 using co-evaporation of the elements at low
Protein-protein interactions (PPIs) play essential roles in biological processes: often proteins interact with each other to exert their functions creating a network of
English borrowed an immense number of words from the French of the Norman invaders, later also from the court French of Isle de France, appropriated a certain number of affixed
