The Neglected Pt−N(sulfonamido) Bond in Pt Chemistry. New Fluorophore-Containing Pt(II) Complexes Useful for Assessing Pt(II) Interactions with Biomolecules

Abstract

Treatment of cis-Pt(Me2SO)2Cl2 with DNSH-tren afforded [Pt(DNSH-tren)Cl]Cl and with DNSH-dienH, under increasingly more basic conditions, led to Pt(DNSH-dienH)Cl(2), Pt(DNSH-dien)Cl, and Pt(DNS-dien). (DNSH = 5-(dimethylamino)naphthalene-1-sulfonyl, linked via a sulfonamide group to tris(2-aminoethyl)amine (DNSH-tren) and diethylenetriamine (DNSH-dienH); the H's in DNSH-dienH designate protons sometimes lost upon Pt binding, i.e., sulfonamide NH for the dienH moiety and H8 for the DNSH moiety). Respectively, the three neutral DNSH-dienH-derived complexes are difunctional, monofunctional, and nonfunctional and exhibit decreasing fluorescence in this order as the dansyl group distance to Pt decreases. 2D NMR data establish that Pt(DNS-dien) has a Pt-C8 bond and a Pt-N(sulfonamido) bond. Pt(DNSH-dien)Cl and [Pt(DNSH-tren)Cl]Cl bind to N7 of 6-oxopurines (e.g., 5'-GMP, 3'-IMP, and 9-ethylguanine) and sulfur of methionine (met). Competition and challenge reactions for Pt(II) with met and 5'-GMP typically reveal that met binding is favored kinetically but that 5'-GMP binding is favored thermodynamically. This common type of behavior was found for [Pt(DNSH-tren)Cl]Cl. In contrast, Pt(DNSH-dien)Cl had reduced kinetic selectivity for met. This unusual behavior undoubtedly arises as a consequence of the bound Pt-N(sulfonamido) group, which donates strongly to Pt (as indicated by relatively upfield dien NH signals) and which places the bulky DNSH moiety close to the monofunctional reaction site. The decrease in the relatively upfield shifts of the DNSH group signals indicates that this group stacks with the purine. This stacking could explain the unprecedented, relatively low reactivity of a Pt complex bearing a dien-type ligand toward met vs 5'-GMP.

In vitro cytotoxic evaluation of novel dichlorodiorgano[N-(2-pyridylmethylene)arylamine]tin(IV) derivatives in human tumor cell lines

“…Following its discovery, there has been considerable exploration of the anti-cancer properties of other transition metal complexes [5][6][7][8][9][10][11][12][13][14][15][16]. Among the metals studied to date, which comprise much of the periodic table, complexes of titanium have shown promise due to high activity against tumors that are resistant to cisplatin combined with low toxicity [13,[17][18][19][20][21][22][23][24][25][26]. In particular, the titanium complexes, e.g., Cp 2 TiCl 2 [bis(cyclopentadienyl)titanium dichloride; titanocene dichloride, 5] and (bzac) 2 -Ti(OEt) 2 [cis-diethoxybis(1-phenylbutane-1,3-dionato)titanium(IV); budotitane, 6] stand out as the first metal-based chemotherapeutics to reach Phase I clinical trials since the development of cisplatin.…”

Transition Metal Ion Complexes of N-alkylguanines

“…The two adjacent nucleobases in these adducts are generally coordinated to the Pt metal via the purine N7 nitrogen atoms which reside in the major groove. [24] 23 (m 1 ura-N 3 ) -(m 1 ura-N 3 ) -(Hm 1 ura-C 5 ) -OH2 1-K + 3 · H2O [25] 24a (m 1 ura-N 3 ) -(m 1 ura-N 3 ) -(Hm 1 ura-C 5 ) -Hm 9 gua 1- [25] 25 DNSH-dienHe 9 gua 1+ [26] 31 dien He 9 gua 2+ [33] 34a (2S,3S)-Me2dab He 9 gua He 9 gua 2+ [36] 34b (2S,3S)-Me2dab 3'-GMP 3'-GMP 0 [36] 34c (2S,3S)-Me2dab 5'-GMP 5'-GMP 0 [36] 35f Me3dien G 2+ [37] 35g Me3dien He 9 gua 2+ [37] 36 (1R, 2R)-dach OD2 OD2 2+ [38] 37 (1R, 2R)-dach He 9 gua OD2 2+ [38] 38 (1R, 2R)-dach He 9 gua He 9 gua 2+ [38] 39 (1S, 2S)-dach He 9 gua He 9 gua 2+ [38] 40 NH3 pic ClCl -0 [28] 41 NH3 pic He 9 gua He 9 gua 2+ 2 · ClO4 -2 · H2O · Me2CO [28] 42 NH3 pic He 9 gua He 9 gua 2+ 2 · NO3 -2 · H2O [28] 43 NH3 pic He 9 gua e 9 gua -1+ NO3 -3.5 · H2O [28] 44 NH3 He 9 gua pic e 9 gua -1+ NO3 -8 · H2O [28] 45 m 1 cyt-N 3 m 1 cyt-N 3 He 9 gua He 9 gua 2+ 2 · NO3 - [29] 46 He 9 gua He 9 gua He 9 gua He 9 gua 2+ 2 · NO3 -2 · KNO3 · 5 · H2O [29] 47 He 9 gua He 9 gua e 9 guae 9 gua -0 [29] A series of new platinum(II) and platinum(IV) complexes, [Pt II (cis-1,4-dach)LCl]NO 3 , (4, 5) and [Pt IV (cis-1,4-dach)Ltrans-(L) 2 Cl]NO 3 (6-9), Schemes (1-3) [where cis-1,4-dach = cis-1,4-diamino-cyclohexane (chelated in a unique twist-boat conformation), L = He 9 gua or Hgua and L = hydroxo (6,8) or acetato (7,9)] have been synthesized by Khokhar et al [19]. The complex [Pt II (cis-1,4-dach)Cl 2 ] (3), Schemes (1) and (2), was prepared and used as a precursor for both type of complexes.…”

“…Therefore, it has become highly desirable to identify features which lessen the affinity of these drugs for sulfur whilst maintaining their ability to interact with the guaninyl N7 or N9 nitrogen atoms. Marzilli et al [26] have investigated the chemistry of Pt complexes containing tridentate ligands incorporating both a sulfonamide and an aromatic fluorescent group [N-(2-((2-aminoethyl)amino)ethyl)-5-(dimethylamino)naphthalene-1-sulfonamide, DNSH-dienH, Scheme (2)]. In the fluorescence spectra recorded for the [Pt II (DNSH-dien)(5'-GMP)] adduct, an additional quenching was observed; this was attributed to energy transfer between the naphthalene ring and the guanine nucleotide.…”

1-[5-(Dimethylamino)-1-naphthylsulfonyl]imidazolidine-2-thione

“…For the applications of compounds containing a 5-(dimethylamino)naphthalene-1-sulfonyl group, see: Corradini et al (1996Corradini et al ( , 1997; Christoforou et al (2006). For a related structure, see: Zhang et al (2009).…”

“…Recently many dansyl derivatives have been reported (Corradini et al, 1996(Corradini et al, ,1997Christoforou et al, 2006). We show great interest in preparing fluorescent probes that are expected to bind to hydrophobic sites in proteins or membranes and have recently published a structure reslted to the title compound (Zhang et al, 2009).…”