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Abstract

Aminoguanidine possesses extensive pharmacological properties. This drug is recognized as a powerful α-dicarbonyl scavenger. In order to better elucidate the reactivity of aminoguanidine with α-dicarbonyls, aminoguanidine was reacted with several aldehydic and diketonic α-dicarbonyls. Electrospray ionization mass spectrometry is a suitable technique to study chemical and biochemical processes and was selected for the purpose. In aminoguanidine reactions, triazines were detected and other compounds that have never been reported before were identified. Triazine precursor forms were detected, namely tetrahydrotriazines and singly dehydrated tetrahydrotriazines. Moreover, species with bicyclic ring structures and dehydrated forms were also identified in aminoguanidine reactions. These species appear to result from tetrahydrotriazines and triazines reactions with one dicarbonyl molecule. Experiments revealed that these bicyclic species, in particular the ones resulting from triazines reactivity, could exist in solution, since they were both identified in the reactions of aminoguanidine and of a selected triazine with the dicarbonyls studied. The results obtained with regard to aminoguanidine/triazines reactivities appear to support the capability of triazines to condensate and form polycyclic ring structures and also to support literature mechanistic data for dihydroimidazotriazines formation via dihydroxyimidazolidine-triazines. The data obtained in this study may prove to be valuable to complement solution information concerning the reactivity of amines with α-dicarbonyls, in particular.

Keywords

aminoguanidine α-dicarbonyls electrospray ionization mass spectrometry aminotriazines

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References

Brownlee

Vlassara

Kooney

Ulrich

Cerami

, “Aminoguanidine prevents diabetes-induced arterial wall protein cross-linking”, Science 232, 1629 (1986). doi: 10.1126/science.3487117

Mišur

Turk

, “Substituted guanidine compounds as inhibitors of nonenzymatic glycation in vitro”, Croat. Chem. Acta. 74, 455 (2001).

Rahbar

Figarola

J.L.

, “Inhibitors and breakers of advanced glycation endproducts (AGEs): A review”, Curr. Med. Chem.—Imun. Endoc. Metab. Agents 2, 135 (2002). doi: 10.2174/1568013023358889

Monnier

V.M.

, “Intervention against the Maillard reaction in vivo”, Arch. Biochem. Biophys. 419, 1 (2003). doi: 10.1016/j.abb.2003.08.014

Thornalley

P.J.

, “Use of aminoguanidine (Pimagedine) to prevent the formation of advanced glycation end-product”, Arch. Biochem. Biophys. 419, 31 (2003). doi: 10.1016/j.abb.2003.08.013

Bharatam

P.V.

Iqbal

Maldi

Tiwari

, “Electron delocalization in aminoguanidine: A computational study”, J. Phys. Chem. A 108, 10509 (2004). doi: 10.1021/jp049366e

Lieber

Smith

G.B.L.

, “The chemistry of aminoguanidine and related substances”, Chem. Rev. 25, 213 (1939). doi: 10.1021/cr60081a003

Wolf

S.P.

, “Aminoguanidine: A drug proposed for prophylaxis in diabetes inhibits catalase and generates hydrogen peroxyde in vitro”, Biochem. Pharmacol. 46, 1139 (1993). doi: 10.1016/0006-2952(93)90461-5

Philis-Tsimikis

Parthasarathy

Picard

Palinski

Witztum

, “Aminoguanidine has both pro-oxidant and antioxidant activity toward LDL”, Arterioscler. Thromb. Vasc. Biol. 15, 367 (1995). doi: 10.1161/01.ATV.15.3.367

10.

Skamarauskas

J.T.

McKay

A.G.

Hunt

J.V.

, “Aminoguanidine and its pro-oxidant effects on an experimental model of protein glycation”, Free Rad. Biol. Med. 21, 801 (1996). doi: 10.1016/0891-5849(96)00183-9

11.

Nohara

Usui

Kinoshita

Watanabe

, “Generation of superoxide anions during the reaction of guanidino compounds with methylglyoxal”, Chem. Pharm. Bull. 50, 179 (2002). doi: 10.1248/cpb.50.179

12.

Price

D.L.

Rhett

P.M.

Thorpe

S.R.

Baynes

J.W.

, “Chelating activity of advanced glycation end-products inhibitors”, J. Biol. Chem. 276, 48967 (2001). doi: 10.1074/jbc.M108196200

13.

Santos

L.S.

Knaack

Metzger

J.O.

, “Investigation of chemical reactions in solution using API-MS”, Int. J. Mass Spectrom. 246, 84 (2005) (and references therein). doi: 10.1016/j.ijms.2005.08.016

14.

Eberlin

M.N.

, “Electrospray ionization mass spectrometry: A major tool to investigate reaction mechanism in both solution and the gas phase”, Eur. J. Mass Spectrom. 13, 19 (2007). doi: 10.1255/ejms.837

15.

Saraiva

M.A.

Borges

C.M.

Florêncio

M.H.

, “Behaviour of 4-(−2-hydroxyethyl)-1-piperazineethane-sulfonic acid under electrospray ionisation mass spectrometry conditions,” Eur. J. Mass Spectrom. 16, 199 (2010). doi: 10.1255/ejms.1061

16.

Erickson

J.G.

, “3-Amino-as-triazines”, J. Am. Chem. Soc. 74, 4706 (1952). doi: 10.1021/ja01138a506

17.

T.W.

Selwood

Thornalley

P.J.

, “Reaction of methylglyoxal with aminoguanidine under physiological conditions and prevention of methylglyoxal binding to plasma proteins”, Biochem. Pharmacol. 48, 1865 (1994). doi: 10.1016/0006-2952(94)90584-3

18.

Constantopoulos

T.L.

Jackson

G.S.

Enke

C.G.

, “Effects of salt concentration on analyte response using electrospray ionization mass spectrometry”, J. Am. Soc. Mass Spectrom. 10, 625 (1999). doi: 10.1016/S1044-0305(99)00031-8

19.

Saraiva

M.A.

Borges

C.M.

Florêncio

M.H.

, “Reactions of a modified lysine with aldehydic and ketonic dicarbonyl compounds: An electrospray mass spectrometry structure activity study”, J. Mass Spectrom. 41, 216 (2006). doi: 10.1002/jms.980

20.

Saraiva

M.A.

Borge

C.M.

Florêncio

M.H.

, “Nonenzymatic model glycation reactions—a comprehensive study of the reactivity of a modified arginine with aldehydic and diketonic dicarbonyl compounds by electrospray mass spectrometry”, J. Mass Spectrom. 41, 755 (2006). doi: 10.1002/jms.1031

21.

Saraiva

M.A.

Borge

C.M.

Florêncio

M.H.

, “Towards the control and inhibition of glycation—the role of the guanidine reaction center with aldehydic and dikeftonic dicarbonyls. A mass spectrometry study. J. Mass Spectrom. 41, 1346 (2006). doi: 10.1002/jms.1109

22.

Sunner

Nicol

Kebarle

, “Factors determining relative sensitivity of analytes in positive mode atmospheric pressure ionization mass spectrometry”, Anal. Chem. 60, 1300 (1988). doi: 10.1021/ac00164a012

23.

Thornalley

P.J.

Yurek-George

Argirov

O.K.

, “Kinetics and mechanism of the reaction of aminoguanidine with the α-oxoaldehydes glyoxal, methylglyoxal, and 3-deoxyglucosone under physiological conditions”, Biochem. Pharmacol. 60, 55 (2000). doi: 10.1016/S0006-2952(00)00287-2

24.

Limanto

Desmond

R.A.

Gauthier

D.R.

Jr Devine

P.N.

Reamer

R.A.

Volante

R.P.

, “A regioselective approach to 5-substituted-3-amino-1,2,4-triazines”, Org. Lett. 5, 2271 (2003). doi: 10.1021/ol034602+

25.

Garnier

Guillard

Pasquinet

Suzenet

Poullain

Jarry

Léger

J.-M.

Lebret

Guillaumet

, “Highly diastereoselective synthesis of C(6)-functionalized dihydroimidazotriazines”, Org. Lett. 5, 4595 (2003). doi: 10.1021/ol035743e

26.

Neunhoeffer

, in Comprehensive heterocyclic chemistry II, Chapter 6.11, Ed by Katrizky

A.R.

Rees

C.W.

Scriven

E.F.V.

, Pergamon Press, Oxford, UK, pp. 507–573 (1996).

27.

Bernhardt

P.V.

Hayes

E.J.

, “Aminotriazines as locking fragments in macrocyclic synthesis”, Inorg. Chem. 37, 4214 (1998). doi: 10.1021/ic980243g

Reactions of Aminoguanidine with α-Dicarbonyl Compounds Studied by Electrospray Ionization Mass Spectrometry

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