Valentin H K Fell, Tim Kramer, Andreas Heindl, Olivia M Merkel
{"title":"Prediction of the Apparent p<i>K</i> <sub>a</sub> Value of Lipid Nanoparticles by Density Functional Theory.","authors":"Valentin H K Fell, Tim Kramer, Andreas Heindl, Olivia M Merkel","doi":"10.1021/acsmaterialsau.4c00158","DOIUrl":null,"url":null,"abstract":"<p><p>One of the most important parameters for the development of novel ionizable lipids (ILs) for use in lipid nanoparticle (LNP) drug carriers is their p<i>K</i> <sub>a</sub> value. Ideally, the LNP should be deprotonated outside the cell to prevent cytotoxicity and protonated inside the endosome, where pH is lower. To achieve this switch, the LNP's p<i>K</i> <sub>a</sub> value, the so-called \"apparent p<i>K</i> <sub>a</sub> value\", should range generally between 5.5 and 7. For specific applications, the range is narrower. We present a straightforward approach to computationally estimate this apparent p<i>K</i> <sub>a</sub> value of LNPs using density functional theory (DFT). This method uses \"surrogates\" of the ILs, which are hypothetical derivatives featuring an <i>N</i>,<i>N</i>-dimethylethylaminium side group attached to the lipid's nitrogen atom.</p>","PeriodicalId":29798,"journal":{"name":"ACS Materials Au","volume":"5 3","pages":"451-457"},"PeriodicalIF":6.5000,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12082357/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Materials Au","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1021/acsmaterialsau.4c00158","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/5/14 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"CHEMISTRY, PHYSICAL","Score":null,"Total":0}
引用次数: 0
Abstract
One of the most important parameters for the development of novel ionizable lipids (ILs) for use in lipid nanoparticle (LNP) drug carriers is their pKa value. Ideally, the LNP should be deprotonated outside the cell to prevent cytotoxicity and protonated inside the endosome, where pH is lower. To achieve this switch, the LNP's pKa value, the so-called "apparent pKa value", should range generally between 5.5 and 7. For specific applications, the range is narrower. We present a straightforward approach to computationally estimate this apparent pKa value of LNPs using density functional theory (DFT). This method uses "surrogates" of the ILs, which are hypothetical derivatives featuring an N,N-dimethylethylaminium side group attached to the lipid's nitrogen atom.
期刊介绍：
ACS Materials Au is an open access journal publishing letters articles reviews and perspectives describing high-quality research at the forefront of fundamental and applied research and at the interface between materials and other disciplines such as chemistry engineering and biology. Papers that showcase multidisciplinary and innovative materials research addressing global challenges are especially welcome. Areas of interest include but are not limited to:Design synthesis characterization and evaluation of forefront and emerging materialsUnderstanding structure property performance relationships and their underlying mechanismsDevelopment of materials for energy environmental biomedical electronic and catalytic applications
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
