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Biochemistry of Buffering Capacity and Ingestion of Buffers In Exercise and Athletic Performance
Published in Peter M. Tiidus, Rebecca E. K. MacPherson, Paul J. LeBlanc, Andrea R. Josse, The Routledge Handbook on Biochemistry of Exercise, 2020
Bryan Saunders, Guilherme G. Artioli, Eimear Dolan, Rebecca L. Jones, Joseph Matthews, Craig Sale
Since stronger acids tend to dissociate more than the weaker ones, the stronger the acid, the higher its Ka value. Likewise, the weaker the acid, the lower its Ka value. Because the Ka values can differ by several orders of magnitude between weak and strong acids, it is convenient to work with their negative logarithms, thereby obtaining the pKa of an acid. Hence, the pKa of an acid represents the negative log of its dissociation constant, as exemplified in Table 22.1.
Site-Specific Chemical Modification of Proteins
Published in Roger L. Lundblad, Chemical Reagents for Protein Modification, 2020
It should follow from the above discussion that the surface of a globular protein is definitely not homogeneous with respect to electrical charge or, more critically for our consideration, with respect to dielectric constant. As a result of this lack of homogeneity, a variety of surface polarities will surround the various functional groups. The physical and chemical properties of any given functional group will be strongly influenced by the nature (e.g., polarity) of the local microenvironment. Changes in the polarity of the microenvironment can have a profound effect on the dissociation of acids. For example consider the effect of the addition of an organic solvent, ethyl alcohol, on the pKa of acetic acid. In 100% H2O, acetic acid has a pKa of 4.70. The addition of 80% ethyl alcohol results in an increase of the pKa to 6.9. In 100% ethyl alcohol the pKa of acetic acid is 10.3. This is particularly important in considering the reactivity of nucleophilic groups such as amino groups, cysteine, carboxyl groups, and the phenolic hydroxyl group. In the case of the primary amines present in protein, these functional groups are not reactive except in the free base form. In other words the proton present at neutral pH must be removed from the ϵ-amino group of lysine before this functional group can function as an effective nucleophile. A listing of the “average” pKa values for the various functional groups present in protein is also given in Table 1.
Curcumin and Neglected Infectious Diseases
Published in Venkatesan Jayaprakash, Daniele Castagnolo, Yusuf Özkay, Medicinal Chemistry of Neglected and Tropical Diseases, 2019
Francesca Mazzacuva, Agostino Cilibrizzi
The enolic structure of curcumin (1) is characterized by the presence of three ionisable protons: one from the enolic proton and two from the phenolic OH groups. Although different values have been attributed to the three acidity constants (Figure 5), it is now accepted that pKa ranges are between 9.5–10.7, 8.5–10.4 and 7.5–8.5, respectively (Priyadarsini 2009). Prototropic equilibria of curcumin.
In-vitro evaluation of dendrimeric formulation of oxaliplatin
Published in Pharmaceutical Development and Technology, 2021
OXA is a white to off-white crystalline powder with a molecular weight of 397.3 g/mol. It is slightly soluble in water (6–7 mg/mL at 20 °C), very slightly soluble in methanol (0.125 mg/mL at 20 °C), almost insoluble in ethanol or acetone (Levi et al. 2000). The pKa value is 6.1 (Matos et al. 2015). It is a third-generation platinum compound designed for preventing cellular resistance as a result of cisplatin and carboplatin use (Raymond, Chaney, et al. 1998). OXA creates cross-linked complexes with DNA and acts by blocking replication (Raymond, Faivre, et al. 1998). The main lesions responsible for cytotoxicity are intra-chain cross-links that occur between active platinum compounds and specific base sequences. These crosslinks are in particular between two adjacent guanine bases or adjacent guanine-adenine bases (Culy et al. 2000).
Efficiency of 123I-ioflupane SPECT as the marker of basal ganglia damage in acute methanol poisoning: 6-year prospective study
Published in Clinical Toxicology, 2021
Katerina Kotikova, David Zogala, Vaclav Ptacnik, Jiri Trnka, Karel Kupka, Manuela Vaneckova, Zdenek Seidl, Pavel Diblik, Jarmila Heissigerova, Tomas Navratil, Martin Komarc, Ivan Zak, Kamila Polakova, Hana Brozova, Sergey Zakharov
Age dependency has been reported for both males and females for DaT SPECT measurements [53]. In the present study, no correlation of the SBR with age and gender was observed. This lack of association can be explained by the relatively homogenous young age of the study population (IQR 35–58 years), small group size, and the capacity of methanol-induced basal ganglia damage to mask age-related DaT decline. Nevertheless, in the multivariate regression model, both age and gender were significantly associated with DaT availability in the putamen. This model demonstrated that arterial blood pH at admission most strongly affected DaT SPECT measurements (Table 3). The dissociation constant of formic acid (pKa) is 3.8, therefore, a pH drop by 0.3 would double the undissociated formic acid levels and produce significant increases in toxicity. This occurs because only undissociated formic acid crosses the blood-brain barrier and reaches neurons of the basal ganglia [54].
Recent advances in the targeting of systemically administered non-viral gene delivery systems
Published in Expert Opinion on Drug Delivery, 2019
Ikramy A. Khalil, Yusuke Sato, Hideyoshi Harashima
The apparent acid dissociation constant (pKa) is an important factor that affects the biodistribution and delivery efficiency of pH-sensitive cationic lipid-containing LNPs [48]. Jayaraman et al. demonstrated that an apparent pKa from 6.2 to 6.5 is optimal for the LNP-mediated hepatic delivery of siRNA through the screening of a series of pH-sensitive cationic lipids with different linker chemistries between hydrophobic scaffolds and amino moieties [49]. Although a lower pKa value promotes hepatocyte uptake through the endogenous ApoE-LDLR pathway due to its neutral properties in the blood stream, it causes an inefficient conversion to cationic properties in acidic endosomes, which results in poor endosomal escape. On the other hand, a higher pKa value means that cationic properties develop in the blood stream which causes enhanced clearance by the reticuloendothelial system and a decreased uptake by hepatocytes due to its cationic properties in the blood stream, which results in non-specific interactions with serum proteins followed by aggregation. Through screening, a DLin-MC3-DMA (MC3) with an apparent pKa of 6.44 was identified as the most potent lipid that showed a 50% effective dose (ED50) of 0.005 mg siRNA/kg in a mouse factor VII (FVII) model [49]. MC3 is currently used as the main component in Patisiran (ONPATTROTM), which is a first-ever RNAi drug [50].