Purpose: Assessment of the accuracy of experimental and theoretical methods of pKa determination for acids and bases as separate classes.
Methods: Four literature pKa datasets were checked for errors and pKa values assigned unambiguously to a single acidic and/or basic ionisation centre. A new chemically diverse and drug-like dataset was compiled from high-throughput UV-vis spectrophotometry pKa data. Measured pKa values were compared with data obtained by alternative methods and predictions by the Epik, Chemaxon and ACD pKa DB software packages.
Results: The pKa values of bases were considerably less accurately predicted than those of acids, in particular for structurally complex bases. Several new chemical motifs were identified for which pKa values were particularly poorly predicted. Comparison of pKa values obtained by UV-vis spectrophotometry and different literature sources revealed that low aqueous solubility and chromophore strength can affect the accuracy of experimental pKa determination for certain bases but not acids.
Conclusions: The pKa prediction tools Epik, Chemaxon and ACD pKa DB provide significantly less accurate predictions for bases compared to acids. Certain chemical features are underrepresented in currently available pKa data sets and as a result poorly predicted. Acids and bases need to be considered as separate classes during pKa predictor development and validation.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/s11095-013-1232-z | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Design of pH-responsive and amphiphilic pullulan-based biological macromolecule for gene delivery.
Int J Biol Macromol
January 2025
Institute of Organic Chemistry and Macromolecular Chemistry (IOMC), Friedrich Schiller University Jena, Humboldtstr. 10, D-07743 Jena, Germany; Jena Center for Soft Matters (JCSM), Friedrich Schiller University Jena, Philosophenweg 7, D-07743 Jena, Germany. Electronic address:
Nanomedicine, particularly gene delivery, holds immense potential and offers promising therapeutic options. Non-viral systems gained attention due to their binding capacity, stability and scalability. Among these, natural polysaccharides, such as pullulan, are advantageous in terms of sustainability, biocompatibility and potential degradability.
View Article and Find Full Text PDFContribution of Weak Bases to Isoxaflutole Hydrolysis: Implications for Hydrolysis in Laboratory and Natural Waters.
Environ Sci Technol
January 2025
Department of Energy, Environmental & Chemical Engineering Washington University in St. Louis, St. Louis, Missouri 63130, United States.
The hydrolysis rates of many organic chemicals are accelerated under alkaline conditions by the presence of hydroxide (HO), which is typically assumed to be the predominant species contributing to base-catalyzed hydrolysis in both natural waters and laboratory buffers used in standard protocols. In this study, we demonstrated that weak bases (e.g.
View Article and Find Full Text PDF5'-Amino-Formyl-Thieno[3,2-]thiophene End-Label for On-Strand Synthesis of Far-Red Fluorescent Molecular Rotors and pH-Responsive Probes.
Bioconjug Chem
January 2025
Departments of Chemistry and Toxicology, University of Guelph, Guelph, Ontario N1G 2W1,Canada.
The ability to label synthetic oligonucleotides with fluorescent probes has greatly expanded their nanotechnological applications. To continue this expansion, it is essential to develop approachable, modular, and tunable fluorescent platforms. In this study, we present the synthesis and incorporation of an amino-formyl-thieno[3,2-]thiophene (AFTh) handle at the 5'-position of DNA oligonucleotides.
View Article and Find Full Text PDFChromatographic analysis and pK evaluation of active pharmaceutical ingredients in anti-metastatic breast cancer: Green vs. conventional RPLC.
J Pharm Biomed Anal
January 2025
Sabanci University Nanotechnology Research and Application Center (SUNUM), Istanbul 34956, Turkey.
This study aimed to determine the chromatographic retention and dissociation/protonation constant (pK) values of lapatinib and tamoxifen, key drugs used in metastatic breast cancer treatment, at 37°C using both conventional and green high-performance liquid chromatography (HPLC) methods. Qualitative analysis was conducted on an XTerra C18 column (250 ×4.6 mm I.
View Article and Find Full Text PDFMEDOC: A Fast, Scalable, and Mathematically Exact Algorithm for the Site-Specific Prediction of the Protonation Degree in Large Disordered Proteins.
J Chem Inf Model
January 2025
Max-Planck-Institut für Immunbiologie und Epigenetik (MPI-IE), Stübeweg 51, 79108 Freiburg im Breisgau, Germany.
Intrinsically disordered regions are found in most eukaryotic proteins and are enriched with positively and negatively charged residues. While it is often convenient to assume that these residues follow their model-compound p values, recent work has shown that local charge effects (charge regulation) can upshift or downshift side chain p values with major consequences for molecular function. Despite this, charge regulation is rarely considered when investigating disordered regions.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!