Hexamethylenetetramine carboxyborane: synthesis, structural characterization and CO releasing properties

Abstract

Carbon monoxide, although widely known as a toxic gas, has received great attention in the past few decades due to its promising role as a medical gas. Several classes of carbon monoxide releasing molecules (CORMs) have been synthesised with many of them having pharmacological activities under physiological conditions. Herein, we report the synthesis and structural characterization of the first example of amine carboxyborane that releases CO under physiological conditions without the aid of inducers. A representative compound hexamethylenetetramine carboxyborane (HMTA-CB) described here has a half-life of 2.7 days and gradually releases CO with the rate constant of 3.0 × 10 s. Its ability to promote cell growth shows the beneficial effect of slow CO release to supplement CO in small amounts over time.

Crystal structure of memantine–carboxyborane

“…The stereogenic centres in the adamantane unit were assigned as C4 S and C8 R in the arbitrarily chosen asymmetric unit but crystal symmetry generates a racemic mixture. The bond lengths [C1-O1 = 1.340 (4), C1-O2 = 1.227 (4) Å ] of the carboxylic acid group are in agreement with the data for related carboxylic acids and known amine-carboxyboranes (Gavezzotti, 2008;Spielvogel et al, 1980;Vyakaranam et al, 2002;Ayudhya et al, 2017). The C-C-C bond angles of the adamantine cage fall within the expected ranges and the N1-C2 bond length at 1.504 (4) Å is comparable with previously reported values in aminoadamantane structures (Donohue & Goodman, 1967;Chacko & Zand, 1973).…”

“…Assessment of available crystal structures deposited with the Cambridge Structural Database (Version 5.39; Groom et al, 2016) indicates that not all amine-carboxyboranes form dimers during crystallization. While some amine-carboxyboranes described above are dimers, others such as piperidine-carboxyborane and hexamethylenetetraminecarboxyborane do not form dimers, suggesting that the aminegroup interaction may influence the overall packing Ayudhya et al, 2017). The extended structure of (I) is shown in projection down the b-and c-axis directions in Fig.…”

“…Our attempt was to mask the compound with an additional moiety that can be removed under certain conditions, therefore releasing the drug. With this goal, memantinecarboxyborane was synthesized since the carboxyborate group is known to decompose into carbon monoxide and boric acid, leaving the drug molecule itself (Ayudhya et al, 2017(Ayudhya et al, , 2018. The single crystal structure of the said compound, (I), was solved and its features are described in this report.…”

Metal-free carbon monoxide-releasing micelles undergo tandem photochemical reactions for cutaneous wound healing

“…Although metal carbonyls hold great promise in both laboratory and clinical investigations, 9,[11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] the development of metal-free CORMs has recently been receiveing increasing attention. 27 In this context, boranocarbonates, 28 CO-releasing prodrugs operated in a "click and release" manner, [29][30][31] and photoresponsive organic CORMs such as 3-hydroxyavone (3-HF) derivatives, [32][33][34][35][36][37] xanthene-9-carboxylic acid, 38 BODIPY derivatives, 39 and aromatic a-diketone derivatives 40 have been developed.…”

Ultrasound Responsive Carbon Monoxide Releasing Micelle

“…1,[4][5][6][7][8][9][10] Some nonmetallic CORMs have also been developed in recent years. [12][13][14][15][16][17][18] CORMs allows convenient administration of a certain dose of CO. In addition, the potential to control the release of CO to a specific target is the major advantage of CORMs over gaseous CO as a therapeutic agent.…”