Please use this identifier to cite or link to this item: https://hdl.handle.net/1959.11/5016
Title: Hydrolysis and Photolysis of 4-Acetoxy-4-(benzothiazol-2-yl)-2,5-cyclohexadien-1-one, a Model Anti-Tumor Quinol Ester
Contributor(s): Wang, Yue-Ting (author); Jin, Kyoung Joo (author); Myers, Lauren R (author); Glover, Stephen  (author)orcid ; Novak, Michael (author)
Publication Date: 2009
Handle Link: https://hdl.handle.net/1959.11/5016
Abstract: 4-Acetoxy-4-(benzothiazol-2-yl)-2,5-cyclohexadien-1-one, 1, a quinol derivative that exhibits significant anti-tumor activity against human breast, colon, and renal cancer cell lines, undergoes hydrolysis in aqueous solution to generate an oxenium ion intermediate, 3, that is selectively trapped by N3 - in an aqueous environment. The 4-(benzothiazol-2-yl) substituent slows the rate of ionization of 1 compared to analogues with 4-phenyl or 4-(p-tolyl) substituents, 4a or 4b. However, once generated, 3 is somewhat more selective than the 4-phenyl-substituted cation 5a. Calculations performed at the B3LYP/6-31G(d) level agree that the 4-(benzothiazol-2-yl) substituent does significantly stabilize 3. The structure of the major isolated azide adduct, 4-(6-azidobenzothiazol-2-yl)phenol, 9, confirms that the positive charge is highly delocalized in 3. The results of hydrolysis of 1 show that the 4-(benzothiazol-2-yl) substituent has a significant inductive electron-withdrawing effect as well as a significant resonance effect that is electron-donating. Photolysis of 1 in aqueous solution generates the quinol 2 as one of several photolysis products. The presence of the quinol suggests that photolysis also leads, in part, to generation of 3, but photoionization of 1 is significantly less efficient than is the case for the esters 4a and 4b. This study proves that 3 is generated by ionization of 1 in an aqueous environment. A significant number of other 2-benzothiazole derivatives that are not quinols, including ring-substituted derivatives of 2-(4-aminophenyl)benzothiazole 15, are under development as anti-tumor agents as well. The possible generation of the reactive intermediate 17 by hydrolysis of the putative metabolite 16 is under investigation.
Publication Type: Journal Article
Source of Publication: Journal of Organic Chemistry, 74(12), p. 4463-4471
Publisher: American Chemical Society
Place of Publication: United States of America
ISSN: 1520-6904
0022-3263
Field of Research (FOR): 030799 Theoretical and Computational Chemistry not elsewhere classified
030505 Physical Organic Chemistry
030401 Biologically Active Molecules
Peer Reviewed: Yes
HERDC Category Description: C1 Refereed Article in a Scholarly Journal
Statistics to Oct 2018: Visitors: 297
Views: 321
Downloads: 0
Appears in Collections:Journal Article

Files in This Item:
2 files
File Description SizeFormat 
Show full item record

Page view(s)

110
checked on Mar 2, 2019
Google Media

Google ScholarTM

Check


Items in Research UNE are protected by copyright, with all rights reserved, unless otherwise indicated.