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Gases
Published in Frank A. Barile, Barile’s Clinical Toxicology, 2019
Cyanic acid (hydrogen cyanate, HCNO) is the starting chemical principle for the various salt forms of cyanide, including the sodium (cyanogran, NaCN), potassium (KCN), and calcium (CaCN) salts. Hydrogen cyanide (HCN, hydrocyanic acid, prussic acid) is a gas and a catalyst and is prepared from the cyanate salts. In addition, the compounds occur naturally as cyanogenic glycosides. The compounds are found from 0.01% to 14% in the seeds of various nuts, including almonds (highest concentration, 2%–14%), cherries, plums, apples, peaches, apricots, pears, plums, and rosaceous plants, as well as in bamboo sprouts and cassava. Figure 25.2 illustrates the hydrolysis of amygdalin, the most widely distributed cyanogenic glycoside. Most hydrolyzing agents, in the presence of the enzyme β-glucuronidase, are capable of producing the hydrolysis products of amygdalin—that is, mandelonitrile glucoside (an intermediate) plus glucose, benzaldehyde, and hydrocyanic acid. Cyanogenic glycosides and hydrolysis of amygdalin.
Chemistries of Chemical Warfare Agents
Published in Brian J. Lukey, James A. Romano, Salem Harry, Chemical Warfare Agents, 2019
Terry J. Henderson, Ilona Petrikovics, Petr Kikilo, Andrew L. Ternay Jr., Harry Salem
Hydrogen cyanide adds chlorine to form cyanogen chloride, which in turn, trimerizes to cyanuric chloride (see Section 2.2.5). A platinum catalyst has been used in the hydrogenation of hydrogen cyanide to produce methylamine (Barratt and Titley, 1919), and a silver or gold catalyst can be used in the high-temperature oxidation of hydrogen cyanide using oxygen. The products of this latter reaction include cyanic acid, HOCN, and lesser amounts of cyanogen, (CN)2 (Zima, 1959). Sodium formate can be produced by reacting hydrogen cyanide with dilute aqueous sodium hydroxide, and the reaction has served as the basis for an analytical method for measuring cyanide (Doizine et al., 1982). Finally, the cyanide ion is a good nucleophile and is able to cleave various bonds, including disulfide bonds, as shown in the following reaction (Gould, 1959):
A review of hydroxyurea-related cutaneous adverse events
Published in Expert Opinion on Drug Safety, 2021
Martin Griesshammer, Kai Wille, Parvis Sadjadian, Frank Stegelmann, Konstanze Döhner
Hydroxyurea (also known as hydroxycarbamide) is an oral chemotherapeutic drug that acts as an antimetabolite. Its mode of action is the reduction of deoxyribonucleotide production by inhibiting the enzyme ribonucleotide reductase through scavenging tyrosyl-free radicals [1]. Dresler and Stein synthesized hydroxyurea (HU) for the first time in 1869 as a so-called substituted urea derivative from hydroxylamine and cyanic acid [2]. As part of a series of experiments on the production of urea derivatives, they produced this simple molecule as a technical exercise in organic chemistry. More than fifty years later, the first biological report on HU was published in 1928 as the result of a study on the toxicity of protein metabolites [3]. In this work, HU was found to cause megaloblastic anemia and a depression in leukocyte formation. In the early 1960s, in vitro studies demonstrated that HU has activity against some tumors [4] as well as leukemia cell lines [5]. However, in subsequent studies, the activity of HU against solid tumors and acute leukemias was inferior to other therapies but HU continued to show particular activity against myeloproliferative neoplasms [6]. In 1967, the Food and Drug Administration (FDA) approved HU for the treatment of solid tumors and chronic myeloid leukemia. Subsequently, the use and approval of HU was extended to BCR-ABL1-negative myeloproliferative neoplasms (hereinafter named as MPN). In addition, 1998 the FDA approved HU for the treatment of adult patients with sickle cell disease (SCD) and in 2017 HU also got approval for SCD in children. In patients with MPN, HU is the most commonly used cytoreductive drug today. Although at the start of therapy the doses of HU used are comparable in SCD and MPN patients, there are fewer reports on HU-related side effects in SCD even with long-term use [7,8]. In the randomized trials comparing HU with placebo in SCD, there was no increase in adverse events associated with HU, particularly with regard to skin toxicities [8]. In the North American MSH study, a multicentre randomized and double blind trial comparing HU with placebo in adults with SCD, there was no increased rate of leg ulcers in the HU group [8,9]. The therapeutic spectrum of HU as an anti-tumor agent is very broad. It is also used in the treatment of HIV [10], chronic myeloid leukemia, essential thrombocytosis, polycythemia vera and sickle-cell anemia [11,12], and in the management of several dermatological conditions including psoriasis [13]. HU acts in the S-phase, causing an arrest of proliferating cell populations in the G1/S phase of the cell cycle [11,14]. The mechanism of action of HU is not completely understood. HU inactivates the enzyme ribonucleotide reductase class I but this agent also might deplete cells via the generation of oxidative stress [15,16]. Moreover, previous reports have indicated that HU kills proliferative cells because it cleaves the DNA molecule directly [17] and affects the DNA by fragmenting the metaphase chromosomes [18].