Video Experimental Relacionado
Updated: May 23, 2026
05:48
Controlled Photoredox Ring-Opening Polymerization of O-Carboxyanhydrides Mediated by Ni/Zn Complexes
Published on: November 21, 2017
Los conjugados degradables de los reactivos de oxanorbornadieno son reactivos de oxanorbornadieno
Alexander A Kislukhin1, Cody J Higginson, Vu P Hong
1Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
Journal of the American Chemical Society
|March 30, 2012
Resumen
Los reactivos de Oxanorbornadienedicarboxilato (OND) permiten la liberación controlada del fármaco de los portadores de albúmina sérica. Al modificar los enlaces OND, las tasas de liberación de fármacos se pueden ajustar de minutos a días para aplicaciones terapéuticas versátiles.
Área de la Ciencia:
- Biología Química Biología química.
- Entrega de drogas Envío de drogas
- Bioconjugación Química de la bioconjugación
Sus antecedentes:
- Las albúminas séricas son portadores macromoleculares clave para la administración de fármacos.
- El desarrollo de mecanismos de liberación de fármacos eficientes y controlables es crucial para la eficacia terapéutica.
Objetivo del estudio:
- Para explorar los reactivos oxanorbornadienedicarboxilato (OND) para la unión y liberación de fármacos de las albúminas séricas.
- Investigar las modificaciones que influyen en la estabilidad de los adductos y la cinética de liberación de fármacos.
Principales métodos:
- Síntesis y caracterización de más de 30 modelos de adductos OND con tiolos y aminas.
- Estudios de cinética de reacción que incluyen cisteína y residuos de aminas de albúmina sérica bovina (BSA).
- Evaluación de la estabilidad de OND-adduct bajo diversas condiciones (pH, temperatura).
- Evaluación de los perfiles de liberación de fármacos utilizando carga fluorescente.
Principales resultados:
- Los reactivos OND etiquetan eficientemente los residuos de cisteína BSA en cuestión de minutos a concentraciones micromolares medias.
- Se observó una alta selectividad (>1000 veces) para el etiquetado de tiol sobre aminas en sistemas modelo, pero el etiquetado de proteínas aminas también es práctico.
- Los adductos de OND-amina exhiben hasta 15 veces mayor estabilidad que los adductos de OND-tiol y son sensibles a la liberación catalizada por ácido.
- Las semividas de liberación de fármacos de BSA oscilaron entre 40 minutos y 7 días, sintonizables mediante la modificación del enlace OND.
Conclusiones:
- Los reactivos OND ofrecen una plataforma versátil para el desarrollo de sistemas sintonizables de liberación de fármacos a partir de portadores de proteínas.
- La capacidad de controlar las tasas de liberación mediante la modificación de los enlaces OND proporciona una herramienta valiosa para las aplicaciones de administración de medicamentos.
Videos de Conceptos Relacionados
00:53Olefin Metathesis Polymerization: Acyclic Diene Metathesis (ADMET)
Acyclic diene metathesis polymerization or ADMET polymerization involves cross-metathesis of terminal dienes, such as 1,8-nonadiene, to give linear unsaturated polymer and ethylene. As ADMET is a reversible process, the formed ethylene gas must be removed from the reaction mixture to complete the polymerization process.
Similar to cross-metathesis, ADMET also involves the formation of metallacyclobutane intermediate by [2+2] cycloaddition of one of the double bonds of a terminal diene with...
Similar to cross-metathesis, ADMET also involves the formation of metallacyclobutane intermediate by [2+2] cycloaddition of one of the double bonds of a terminal diene with...
03:08Hydroboration-Oxidation of Alkenes
In addition to the oxymercuration–demercuration method, which converts the alkenes to alcohols with Markovnikov orientation, a complementary hydroboration-oxidation method yields the anti-Markovnikov product. The hydroboration reaction, discovered in 1959 by H.C. Brown, involves the addition of a B–H bond of borane to an alkene giving an organoborane intermediate. The oxidation of this intermediate with basic hydrogen peroxide forms an alcohol.
02:47Alkynes to Aldehydes and Ketones: Hydroboration-Oxidation
Introduction
One of the convenient methods for the preparation of aldehydes and ketones is via hydration of alkynes. Hydroboration-oxidation of alkynes is an indirect hydration reaction in which an alkyne is treated with borane followed by oxidation with alkaline peroxide to form an enol that rapidly converts into an aldehyde or a ketone. Terminal alkynes form aldehydes, whereas internal alkynes give ketones as the final product.
One of the convenient methods for the preparation of aldehydes and ketones is via hydration of alkynes. Hydroboration-oxidation of alkynes is an indirect hydration reaction in which an alkyne is treated with borane followed by oxidation with alkaline peroxide to form an enol that rapidly converts into an aldehyde or a ketone. Terminal alkynes form aldehydes, whereas internal alkynes give ketones as the final product.
02:04Oxidation of Alkenes: Anti Dihydroxylation with Peroxy Acids
Diols are compounds with two hydroxyl groups. In addition to syn dihydroxylation, diols can also be synthesized through the process of anti dihydroxylation. The process involves treating an alkene with a peroxycarboxylic acid to form an epoxide. Epoxides are highly strained three-membered rings with oxygen and two carbons occupying the corners of an equilateral triangle. This step is followed by ring-opening of the epoxide in the presence of an aqueous acid to give a trans diol.
02:01Alkynes to Carboxylic Acids: Oxidative Cleavage
Alkynes undergo oxidative cleavage in the presence of oxidizing reagents like potassium permanganate and ozone. The triple bond — one σ bond and two π bonds — is completely cleaved, and the alkyne is oxidized to carboxylic acids. When warm and basic aqueous potassium permanganate is used as an oxidizing agent, alkynes are first converted to carboxylate salts via an unstable α-diketone intermediate. Further, a mild acid treatment protonates the carboxylate anions generating free carboxylic acid...
02:36Regioselectivity and Stereochemistry of Hydroboration
A significant aspect of hydroboration–oxidation is the regio- and stereochemical outcome of the reaction.
Hydroboration proceeds in a concerted fashion with the attack of borane on the π bond, giving a cyclic four-centered transition state. The –BH2 group is bonded to the less substituted carbon and –H to the more substituted carbon. The concerted nature requires the simultaneous addition of –H and –BH2 across the same face of the alkene giving syn stereochemistry.
Hydroboration proceeds in a concerted fashion with the attack of borane on the π bond, giving a cyclic four-centered transition state. The –BH2 group is bonded to the less substituted carbon and –H to the more substituted carbon. The concerted nature requires the simultaneous addition of –H and –BH2 across the same face of the alkene giving syn stereochemistry.