PMID: 11325274Apr 28, 2001Paper

The secondary amine/nitric oxide complex ion R(2)N[N(O)NO](-) as nucleophile and leaving group in S9N)Ar reactions

The Journal of Organic Chemistry
Joseph E SaavedraLarry K Keefer

Abstract

Ions of structure R(2)N[N(O)NO](-) and their alkylation products have seen increasing use as nitric oxide (NO)-generating agents for biomedical research applications. Here we show that such diazeniumdiolate anions can readily displace halide from a variety of electrophilic aza- or nitroaromatic substrates to form O(2)-arylated derivatives of structure R(2)N-N(O)=N-OAr. The site of arylation and the cis arrangement of the oxygens were confirmed by X-ray crystallography. Displacement by various nucleophiles showed R(2)N[N(O)NO](-) to be a reasonably good leaving group, with rate constants for displacement by hydroxide, methoxide, and isopropylamine that were between those of chloride and fluoride in the S(N)Ar reactions we surveyed. The Meisenheimer intermediate could be spectrally observed. These O(2)-aryl diazeniumdiolates proved capable of reacting with the nucleophilic sulfur of the HIV-1 p7 nucleocapsid protein's zinc finger assembly to eject the zinc, disrupting a structural motif critical to viral replication and suggesting possible utility in the drug discovery realm.

References

Jan 1, 1996·Methods in Enzymology·G N WelchJ Loscalzo
Sep 30, 1999·Bioconjugate Chemistry·J A HrabieL K Keefer
Jan 29, 2000·Journal of Medicinal Chemistry·J E SaavedraL K Keefer

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Citations

Mar 17, 2010·Investigational New Drugs·Steven HutchensDanyelle M Townsend
Oct 31, 2012·Chemical Research in Toxicology·Ryan J HollandLarry K Keefer
Jul 1, 2010·Chemical Communications : Chem Comm·Debanjan BiswasJoseph A Hrabie
May 11, 2011·Chemical Communications : Chem Comm·Rahul S NandurdikarJoseph E Saavedra
Oct 6, 2010·The Journal of Experimental Medicine·Jonathan M WeissRobert H Wiltrout
Oct 22, 2010·The Journal of Pharmacology and Experimental Therapeutics·Anna E MaciagLarry K Keefer
Jan 15, 2011·Journal of Leukocyte Biology·David A WinkCarol A Colton
Oct 22, 2014·Pharmaceutical Research·Imit KaurPaul J Shami
Aug 26, 2014·Frontiers in Pediatrics·Rupeng ZhuoWen Luo
Aug 21, 2010·The Journal of Pharmacy and Pharmacology·Tanyel KiziltepePaul J Shami
Apr 23, 2004·Molecular Pharmacology·Victoria J FindlayKenneth D Tew
Nov 26, 2019·Chemical Communications : Chem Comm·Dongsik ParkWon Jong Kim
Dec 1, 2015·Journal of Biochemical and Molecular Toxicology·Ling LiuShuying Wang
Feb 23, 2020·Chemical Communications : Chem Comm·Thomas FellowesJonathan M White
May 11, 2012·Chemical Communications : Chem Comm·Debanjan BiswasJoseph E Saavedra
Mar 15, 2020·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·G KaurM Verma
Nov 22, 2020·Journal of Hazardous Materials·Jiajia Liu, Yingjie Xu
Mar 13, 2021·Pharmacological Reports : PR·Kamal S AbdelrahmanMohamed Abdel-Aziz
Dec 8, 2005·The Journal of Physical Chemistry. a·D Scott BohleYan-Ni Wang
May 16, 2017·Journal of Medicinal Chemistry·Zhangjian HuangYihua Zhang
Mar 14, 2020·The Journal of Organic Chemistry·Nabeelah I KauserAmjad Ali

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