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Precipitation and Acid/Base Aqueous Reactions
Published in Patrick E. McMahon, Rosemary F. McMahon, Bohdan B. Khomtchouk, Survival Guide to General Chemistry, 2019
Patrick E. McMahon, Rosemary F. McMahon, Bohdan B. Khomtchouk
Use of the neutral base NH3 produces a variation in the exchange process. Transfer of an H+ forms the ammonium cation (NH4+), which then combines with the remainder of the acid molecule to form only one final ionic product when viewed as a formula equation. The equation is balanced; NH3 always accepts only one transferred H+.
NUTRIENT HOMEOSTASIS
Published in David M. Gibson, Robert A. Harris, Metabolic Regulation in Mammals, 2001
David M. Gibson, Robert A. Harris
Similarly the liver can utilize the twenty different amino acids arriving in the portal blood for its own oxidative metabolism and protein synthesis. However the bulk of the inllux passes into the general circulation for uptake by the peripheral tissues. If there is a prolonged dietary surfeit of amino acids (roast beef) the carbon skeletons will be oxidized in the liver w hile the amino groups are pruned and incorporated into urea for linai excretion by the kidney. In this situation the systemic blood is spared an excess of amino acids which could exceed the abilit\ of peripheral cells to manage the disposal of amino groups. Ammonia (NH,) and its protonated form, the ammonium cation (NH/), are toxic. Tissues incorporate N11,' into the amide ol the amino acid glutamic for transport to the liver, the exclusive site of urea formation, Chapter 8.
Uro-Angiographic Contrast Agents—The Holy Grail
Published in Christoph de Haën, X-Ray Contrast Agent Technology, 2019
Around 1968, Philip E. Wiegert at Mallinckrodt Chemical Works synthesized a trimeric analog of iothalamate (Figure 4.26, 18) and submitted a first version of a US patent application (Wiegert 1968). The molecule possessed three carboxylic groups, one of which was neutralized by internal salt formation with a tertiary ammonium cation. The trimeric molecule carrying nine iodine atoms per molecule responded convincingly to the reigning contrast agent design principle. At the same time, it introduced the idea of offsetting a negative electric charge by a positive charge internal to the molecule. This idea contributed to the next generation of contrast agent design principles, that of maximizing the I/P ratio. More about this later. In the trimeric molecule, this ratio assumed a value of 3.0. Like before with the dimeric molecule, iocarmate, Hilal was involved in testing biologically the trimeric relative (Hilal and Morgan 1968; Hilal 1970). Hilal’s concern with the osmolality of contrast agents and previous collaboration with Mallinckrodt Chemical Works may have fostered the decision of the company to synthesize a trimeric molecule, but as already mentioned for the dimeric analog, Hoey has denied having followed a suggestion by Hilal (1970). Efforts to procure a copy of Hilal’s claimed presentation of the trimer at the annual congress of the RSNA in 1968 and cited as Hilal and Morgan (1968) in Hilal (1970) have failed. In any case, Wiegert’s (1968) initial patent application preceded by at least 2 days the congress. Notwithstanding presumably favorable osmolalities of its solution, the trimeric molecule was never developed further. Oligomers even higher than trimers, as well as polymers, will be dealt with later in this chapter.
Tuning the activity of iminosugars: novel N-alkylated deoxynojirimycin derivatives as strong BuChE inhibitors
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2021
Ana I. Ahuja-Casarín, Penélope Merino-Montiel, José Luis Vega-Baez, Sara Montiel-Smith, Miguel X. Fernandes, Irene Lagunes, Inés Maya, José M. Padrón, Óscar López, José G. Fernández-Bolaños
On the one hand, N-alkyl-DNJ derivatives could be partially protonated at physiological pH, thus mimicking the ammonium cation of acetylcholine, and enabling favourable interactions within the CAS. Although it has been reported that the presence of aromatic substituents connected to iminosugars through a short alkyl tether (2–3 carbon atoms) leads to pKa of 6.037 or below 6.038, because of the electron-withdrawing effect of the aryl moiety, compounds prepared herein, with longer alkyl fragments are expected to tentatively exhibit higher pKa values, probably in between for those reported for N-nonyl-DNJ and N-butyl-DNJ (6.7 and 7.1, respectively)39. On the other hand, as aforementioned, 1-DNJ has positive effects against amyloidogenesis. Moreover, 1-DNJ has recently been found40 to ameliorate stable angina pectoris in patients with coronary heart disease by reducing inflammatory responses and by increasing the antioxidant machinery. Taking into consideration that profound oxidative stress and neuroinflammation are common features of Alzheimer’s disease41, the use of 1-DNJ as the pharmacophore might also provide activity against other targets of this multifactorial disease. Furthermore, different substitution patterns on the aromatic appendage might modulate the interactions within the PAS region.
Development of potent reversible selective inhibitors of butyrylcholinesterase as fluorescent probes
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2020
Stane Pajk, Damijan Knez, Urban Košak, Maja Zorović, Xavier Brazzolotto, Nicolas Coquelle, Florian Nachon, Jacques-Philippe Colletier, Marko Živin, Jure Stojan, Stanislav Gobec
With the discovery of the picomolar selective BChE inhibitor 217, the design of an inhibitor with a fluorophore part positioned in the acyl binding pocket was revisited. We hypothesised that the loss of binding affinity that resulted from the substitution of naphthalene with coumarin might be compensated for by the strong cation-π interactions between its dimethylamino group and Trp82, as seen in the crystal structure of inhibitor 2 in complex with BChE17. Compounds 2A and 2B were synthesised without the piperidine moiety of the parent inhibitor 2 (Figure 2). Additionally, the diethylamino group at position 7 of the coumarin scaffold was substituted with a less bulky dimethylamino group. To increase the interactions at the choline binding site, a compound with a permanent charge (2B) was designed, on the basis that compounds with a permanent ammonium cation can produce significantly stronger cation-π interactions compared with compounds with a tertiary amine moiety in the same position37. Indeed, the trimethylammonium fragment mimics the quarternary amine in substrate BSCh. Unfortunately, compounds 2A and 2B showed very low and unselective inhibition of BChE. Naphthalene was seen to be the optimal fit for the acyl binding pocket, and substitution with coumarin resulted in loss of inhibitory activity.
Functional paclitaxel plus honokiol micelles destroying tumour metastasis in treatment of non-small-cell lung cancer
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2018
Xin Wang, Lan Cheng, Hong-Jun Xie, Rui-Jun Ju, Yao Xiao, Min Fu, Jing-Jing Liu, Xue-Tao Li
Dequalinium (DQA) is a quaternary ammonium cation. As a kind of mitochondrial-targeted drug, DQA can selectively accumulated in the mitochondria of cancer cells. Some previous studies had demonstrated that the modification of DQA on the liposomal surface could increase the cellular uptake by electrostatic interactions [14,15]. Honokiol is an active natural extract of traditional Chinese herb Magnolia offcinalis, and it is widely used as a supplementary functional drug in treatment of cancer for the various biological properties such as inhibiting the VM channels, suppressing the invasion of cancer cells and reducing the adhesion rate between cancer cells and body environment [16,17]. Paclitaxel is one of the most effective chemotherapy drugs for treating various kinds of cancer. The underlying mechanism for the cytotoxicity of paclitaxel is mainly from binding tubulin and stabilizing microtubules. These stable microtubules inhibit the division of cancer cells at the G2/M phase of cell cycle [18,19]. Therefore, the combination of paclitaxel plus honokiol was considered for the preparation of micelles. In this way, the proliferation of lung cancer cells was restricted by paclitaxel, and cellular metastases and VM channels were suppressed by honokiol in the meanwhile. This combination fundamentally solved the problem of tumor metastasis which was inevitable for traditional chemotherapy when killing cancer cells.