Related Experiment Video
Updated: May 26, 2026
08:46
Preparation and Reactivity of a Triphosphenium Bromide Salt: A Convenient and Stable Source of Phosphorus(I)
Published on: November 22, 2016
Development of an efficient method for phosphorodiamidate bond formation by using inorganic salts
Taro Harakawa1, Hirosuke Tsunoda, Akihiro Ohkubo
1Department of Life Science, Tokyo Institute of Technology, 4259 Nagatsutacho, Midoriku, Yokohama 226-8501, Japan.
Bioorganic & Medicinal Chemistry Letters
|January 10, 2012
Summary
Researchers improved phosphorodiamidate morpholino oligonucleotide (PMO) synthesis by adding inorganic salts. Lithium bromide significantly accelerated PMO chain elongation, enhancing antisense strategy development.
Area of Science:
- Oligonucleotide Chemistry
- Medicinal Chemistry
- Molecular Biology
Background:
- Phosphorodiamidate morpholino oligonucleotides (PMOs) are vital for antisense gene regulation due to stability and low toxicity.
- Current PMO synthesis is hindered by slow chain elongation, necessitating more efficient phosphodiamidate bond formation methods.
Purpose of the Study:
- To investigate additives for enhancing phosphodiamidate bond formation during PMO synthesis.
- To identify specific reagents that accelerate PMO chain elongation.
Main Methods:
- Screening various additives, including inorganic salts, in the reaction media for PMO synthesis.
- Quantifying the reaction rate improvements with different additives.
Main Results:
- Certain inorganic salts effectively improved phosphodiamidate bond formation efficiency.
- Lithium bromide demonstrated the most significant effect, accelerating PMO synthesis approximately 10-fold.
Conclusions:
- Inorganic salt additives, particularly lithium bromide, can substantially enhance PMO synthesis efficiency.
- This finding offers a promising strategy for faster development of PMO-based therapeutics and research tools.
Related Concept Videos
01:14Photoluminescence: Applications
Photoluminescence offers a wide range of applications due to its inherent sensitivity and selectivity. This technique allows for both direct and indirect analyses of the analyte. Direct quantitative analysis is possible when the analyte exhibits a favorable quantum yield for fluorescence or phosphorescence. However, an indirect analysis may be feasible if the analyte is not fluorescent or phosphorescent, or if the quantum yield is unfavorable. Indirect methods include reacting the analyte with...
01:15α-Bromination of Carboxylic Acids: Hell–Volhard–Zelinski Reaction
The method to achieve α-brominated carboxylic acids using a mixture of phosphorus tribromide and bromine is known as the Hell–Volhard–Zelinski reaction. The reaction is catalyzed by phosphorus tribromide, which can be used directly or produced in situ from red phosphorus and bromine. The mechanism comprises PBr3 catalyzed conversion of acid to acid bromide and hydrogen bromide. The acid bromide enolizes to its enol form in the presence of HBr. The nucleophilic enol attacks the bromine molecule...
01:19Diazonium Group Substitution: –OH and –H
Nitrous acid, a weak acid, is prepared in situ via the reaction of sodium nitrite with a strong acid under cold conditions. This nitrous acid prepared in situ reacts with primary arylamines to form arenediazonium salts. Such reactions are known as diazotization reactions. As shown in Figure 1, the formation of arenediazonium salts begins with the decomposition of nitrous acid in an acidic solution to give nitrosonium ions.
01:14Nucleophilic Aromatic Substitution of Aryldiazonium Salts: Aromatic SN1
Treating arylamines with nitrous acid gives aryldiazonium salts that are effective substrates in nucleophilic aromatic substitution reactions. The diazonio group in these salts can be easily displaced by different nucleophiles, yielding a wide variety of substituted benzenes. The leaving group departs as nitrogen gas, and this easy elimination is the driving force for the substitution reaction.
In the Sandmeyer reaction, for example, the diazonio group is replaced by a chloro, bromo, or cyano...
In the Sandmeyer reaction, for example, the diazonio group is replaced by a chloro, bromo, or cyano...
01:11Aryldiazonium Salts to Azo Dyes: Diazo Coupling
The reaction of weakly electrophilic aryldiazonium (also called arenediazonium) salts with highly activated aromatic compounds leads to the formation of products with an —N=N— link, called an azo linkage. This reaction, presented in Figure 1, is known as diazo coupling and occurs without the loss of the nitrogen atoms of the aryldiazonium salt. Highly activated aromatic compounds such as phenols or arylamines favor the diazo coupling reaction. The coupling generally occurs at the para position.
00:49Gravimetry: Inorganic And Organic Precipitating Agents
In gravimetry, the precipitant is chosen carefully to obtain a pure solid that can be easily filtered. Common inorganic precipitants can be used to determine several cations and anions. In some cases, the formation of the same precipitate can be used to determine the cation and the anion. For example, the reaction of barium and chromate ions to give barium chromate is used to determine both barium and chromate. However, precipitates such as hydroxides, oxalates, and metal ammonium phosphates...