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Related Concept Videos

Cycloaddition Reactions: Overview01:16

Cycloaddition Reactions: Overview

2.7K
Cycloadditions are one of the most valuable and effective synthesis routes to form cyclic compounds. These are concerted pericyclic reactions between two unsaturated compounds resulting in a cyclic product with two new σ bonds formed at the expense of π bonds. The [4 + 2] cycloaddition, known as the Diels–Alder reaction, is the most common. The other example is a [2 + 2] cycloaddition.
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Thermal and Photochemical Electrocyclic Reactions: Overview01:26

Thermal and Photochemical Electrocyclic Reactions: Overview

2.4K
Electrocyclic reactions are reversible reactions. They involve an intramolecular cyclization or ring-opening of a conjugated polyene. Shown below are two examples of electrocyclic reactions. In the first reaction, the formation of the cyclic product is favored. In contrast, in the second reaction, ring-opening is favored due to the high ring strain associated with cyclobutene formation.
2.4K
Cycloaddition Reactions: MO Requirements for Thermal Activation01:16

Cycloaddition Reactions: MO Requirements for Thermal Activation

3.6K
Thermal cycloadditions are reactions where the source of activation energy needed to initiate the reaction is provided in the form of heat. A typical example of a thermally-allowed cycloaddition is the Diels–Alder reaction, which is a [4 + 2] cycloaddition. In contrast, a [2 + 2] cycloaddition is thermally forbidden.
3.6K
Cycloaddition Reactions: MO Requirements for Photochemical Activation01:12

Cycloaddition Reactions: MO Requirements for Photochemical Activation

2.1K
Some cycloaddition reactions are activated by heat, while others are initiated by light. For example, a [2 + 2] cycloaddition between two ethylene molecules occurs only in the presence of light. It is photochemically allowed but thermally forbidden.
2.1K
[4+2] Cycloaddition of Conjugated Dienes: Diels–Alder Reaction01:16

[4+2] Cycloaddition of Conjugated Dienes: Diels–Alder Reaction

10.3K
The Diels–Alder reaction is an example of a thermal pericyclic reaction between a conjugated diene and an alkene or alkyne, commonly referred to as a dienophile. The reaction involves a concerted movement of six π electrons, four from the diene and two from the dienophile, forming an unsaturated six-membered ring. As a result, these reactions are classified as [4+2] cycloadditions.
10.3K
Olefin Metathesis Polymerization: Acyclic Diene Metathesis (ADMET)00:53

Olefin Metathesis Polymerization: Acyclic Diene Metathesis (ADMET)

2.0K
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...
2.0K

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A Concise Synthetic Approach to Highly Reactive Click-to-Release Trans-Cyclooctene Linkers.

Bing Liu1, Wolter Ten Hoeve2, Ron M Versteegen3

  • 1Tagworks Pharmaceuticals, Toernooiveld 1, 6525 ED, Nijmegen, The Netherlands.

Chemistry (Weinheim an Der Bergstrasse, Germany)
|May 24, 2023
PubMed
Summary

Researchers developed a faster click-to-release reaction for drug delivery using novel trans-cyclooctenes (TCOs). The new sTCO linkers show improved reactivity and stability for in vivo applications.

Keywords:
cleavable linkersclick chemistryiodolactonizationpyridazine eliminationtrans-cyclooctene

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Area of Science:

  • Chemical Biology
  • Organic Synthesis
  • Drug Delivery Systems

Background:

  • Click-to-release reactions are crucial for drug delivery, with trans-cyclooctenes (TCO) and tetrazines being key components.
  • Increasing the reaction rate of TCO-tetrazine click-to-release systems can enhance drug delivery efficiency.

Purpose of the Study:

  • To develop a novel, highly reactive trans-cyclooctene (sTCO) derivative for improved click-to-release applications.
  • To synthesize sTCOs via a short and stereoselective route.
  • To evaluate the in vivo stability and payload release capabilities of the new sTCO linkers.

Main Methods:

  • Developed a stereoselective synthesis for novel trans-cyclooctene (sTCO) derivatives.
  • Quantified tetrazine-triggered payload release kinetics.
  • Assessed in vivo stability of sTCOs as antibody linkers in mouse models.

Main Results:

  • Achieved a fivefold increase in reactivity for the developed sTCOs compared to existing TCOs.
  • Demonstrated quantitative tetrazine-triggered payload release.
  • Confirmed comparable in vivo stability of sTCOs to current TCO linkers in circulation.

Conclusions:

  • The novel sTCOs offer a significant advancement in click-to-release chemistry for drug delivery.
  • The developed synthesis route is efficient and stereoselective.
  • These highly reactive and stable sTCO linkers hold great promise for advanced drug delivery applications.