生物適合性スクリーニングの一環としてLogPの決定
Marko Turkalj1, Siemon De Nys1, Jeroen Vanoirbeek2
1KU Leuven, Department of Oral Health Sciences, BIOMAT & UZ Leuven, Dentistry, Leuven, Belgium.
まとめ
複合モノメアの実験的に決定されたオクタノール-水分割係数 (logP) 値は,生物蓄積リスクを評価する上で極めて重要です. in vitro測定は,現在のin-silicoモデルよりも信頼性が高く,logPを過剰に予測する傾向があります.
科学分野:
- 毒理学 毒理学 毒理学
- 環境科学 環境科学
- マテリアルサイエンス 材料科学
背景:
- オクタノール-水分割係数 (logP) は,生物蓄積と環境リスクの予測に不可欠です.
- 複合モノメアの生物互換性を評価するために,正確なlogP決定は不可欠です.
研究 の 目的:
- シェイクフラスク法を使用して複合モノマーのlogPを実験的に決定する.
- 実験的な logP 値と,in-silico モデルによって予測された値を比較する.
- logP予測のためのin-silicoモデルの信頼性を評価する.
主な方法:
- 複合モノマー (BisEMA3,BisEMA6,BisEMA10,BisGMA,HEMA,TEGDMA,UDMA) は,logPの決定のためにシェイクフラスク法に従った.
- 均衡は24,48,72時間にわたって実施され,その後はUHPLC-MS/MS分析が行われました.
- In-silico logP予測は,KOWWIN,ACD/LogP,XLogP3モデルを使用して生成されました.
主要な成果:
- 時間点 (p > 0.05) の間にlogPの有意な差は観察されず,24時間後に均衡が示された.
- 72時間の実験 logP 値は,4.05 ± 0.09 (BisEMA10) から 0.09 ± 0.03 (HEMA) までの範囲でした.
- インシリコンモデルは,特に水害性の高いモノマーについて,一貫してlogP値を過剰に予測しました.
結論:
- 現在のin-silicoモデルの信頼性が低いため,in vitro logP決定が推奨されています.
- 実験的に決定されたlogP値は,in-silico予測よりも低かったため,生物蓄積の可能性が低いことが示唆された.
- in-silicoモデルのさらなる開発には,実験的に検証された logP 値の大規模なデータセットが必要です.
関連する概念動画
02:53Determining Order of Reaction
62.7K
Rate laws describe the relationship between the rate of a chemical reaction and the concentration of its reactants. In a rate law, the rate constant k and the reaction orders are determined experimentally by observing how the rate of reaction changes as the concentrations of the reactants are changed. A common experimental approach to the determination of rate laws is the method of initial rates. This method involves measuring reaction rates for multiple experimental trials carried out using...
62.7K
01:51Determination
21.1K
During embryogenesis, cells become progressively committed to different fates through a two-step process: specification followed by determination. Specification is demonstrated by removing a segment of an early embryo, “neutrally” culturing the tissue in vitro—for example, in a petri dish with simple medium—and then observing the derivatives. If the cultured region gives rise to cell types that it would normally generate in the embryo, this means that it is specified. In...
21.1K
02:46Genetic Screens
5.8K
Genetic screens are tools used to identify genes and mutations responsible for phenotypes of interest. Genetic screens help identify individuals or a group of people at risk of developing genetic diseases and help them with early intervention, targeted therapy, and reproductive options.
Forward genetic screens
Forward or “classical” genetic screens involve creating random mutations in an organism’s DNA using radiation, mutagens, or insertion of additional bases, which...
Forward genetic screens
Forward or “classical” genetic screens involve creating random mutations in an organism’s DNA using radiation, mutagens, or insertion of additional bases, which...
5.8K
04:08Determining the pH of Salt Solutions
48.3K
The pH of a salt solution is determined by its component anions and cations. Salts that contain pH-neutral anions and the hydronium ion-producing cations form a solution with a pH less than 7. For example, in ammonium nitrate (NH4NO3) solution, NO3− ions do not react with water whereas NH4+ ions produce the hydronium ions resulting in the acidic solution. In contrast, salts that contain pH-neutral cations and the hydroxide ion-producing anions form a solution with a pH greater than 7. For...
48.3K
03:08Rate-Determining Steps
37.6K
Relating Reaction Mechanisms
In a multistep reaction mechanism, one of the elementary steps progresses significantly slower than the others. This slowest step is called the rate-limiting step (or rate-determining step). A reaction cannot proceed faster than its slowest step, and hence, the rate-determining step limits the overall reaction rate.
The concept of rate-determining step can be understood from the analogy of a 4-lane freeway with a short-stretch of traffic-bottleneck caused due to...
In a multistep reaction mechanism, one of the elementary steps progresses significantly slower than the others. This slowest step is called the rate-limiting step (or rate-determining step). A reaction cannot proceed faster than its slowest step, and hence, the rate-determining step limits the overall reaction rate.
The concept of rate-determining step can be understood from the analogy of a 4-lane freeway with a short-stretch of traffic-bottleneck caused due to...
37.6K
02:37Experimental Determination of Chemical Formula
47.8K
The elemental makeup of a compound defines its chemical identity, and chemical formulas are the most concise way of representing this elemental makeup. When a compound’s formula is unknown, measuring the mass of its constituent elements is often the first step in determining the formula experimentally.
47.8K