DOI: 10.1002/asia.201201148

Exploring Nitrogen Ligand Diversity in trans-N-Heterocyclic Carbene–Amine Platinum Complexes : Synthesis, Characterization, and Application to

Fluorescence

Edith Chardon,[a, b] Georges Dahm,[a] Gilles Guichard,*[b] andSt�phane Bellemin-Laponnaz*[a]

Introduction

N-Heterocyclic carbenes (NHC)[1] have become ubiquitousligands in organometallic chemistry[2] with many diversifiedapplications ranging from homogeneous catalysis to materi-al[3] and even to medicinal sciences.[4] Indeed, the high stabil-ity of their corresponding complexes and the ease of deriva-tization of the NHC-ligand make them suitable candidatesfor drug development. Apart from the antimicrobial proper-ties demonstrated by various gold(I),[5,6] silver(I),[7] rutheniu-m(II), and rhodium(I) derivatives,[8] NHC complexes oftransition metals have also been highlighted as promisingagents for anticancer applications.[4] For that purpose, sever-al transition metal NHC complexes have been studied; spe-cifically, those of gold,[9] silver,[10] copper,[10b] palladium,[6,11]

and platinum[12] display antitumor activities at differentlevels and along various pathways. Among them, the devel-opment of platinum-based complexes is of great interest toovercome the limitations encountered with the use of theworld�s best-selling anticancer drug cisplatin, for example,the severe side toxicities sometimes accompanied by ac-quired cell-resistance mechanisms during the treatment.Indeed, it has been shown by Marinetti et al. that trans-con-figured platinum complexes of the general formula(NHC)PtX2(L) (L =amine, Figure 1) are efficient againsta variety of cancer cell lines, including cisplatin-resistantcells.[12a,b] In addition, Che and coworkers reported the useof cationic platinum complexes of the general formula[(NHC)Pt ACHTUNGTRENNUNG(C N N)]+ (Figure 1) as highly cytotoxic anticancer

agents against HeLa (cervical cancer) and HepG2 (hepato-cellular carcinoma) cell lines.[12c]

The development of modular approaches to introducechemical diversity is of great importance in this field. In par-ticular, the chemoselective functionalization directly ona preformed metal complex represents an attractive strategyfor the introduction of specific features (i.e., water solubility,specific cell recognition, delivery, fluorescence, etc.) at thevery last step of the synthesis.[13] We have previously appliedruthenium-catalyzed 1,3-dipolar cycloaddition on PdII andPtII-NHC complexes to conjugate polyethylene glycol(PEG) derivatives as well as oestrogen receptor ligands.[14]

More recently, we have described the non-covalent and se-lective functionalization of a stable preformed (NHC)PtI2ACHTUNGTRENNUNG(pyridine) complex by ligand substitution of the pyridinewith various nitrogen-based ligands to generate novel cyto-toxic platinum complexes (Scheme 1).[15] This simple strat-egy provides a straightforward method to the synthesis ofthese complexes, which were previously obtained via a two-step method from the sensitive Karsted catalyst.[12] Herein,we report the synthesis and characterization of an expandedand diversified set of trans-NHC platinum complexes alongwith the X-ray structure determination for eight of them.We also performed NMR kinetic studies and competitionexperiments on the ligand substitution in order to gain moreinsights into the mechanism of exchange. Finally, we synthe-sized platinum NHC complexes with fluorescent propertiessince ligand exchange allows easy fluorescent labeling of the

[a] Dr. E. Chardon, Dr. G. Dahm, Dr. S. Bellemin-LaponnazInstitut de Physique et Chimie des Mat�riaux de StrasbourgUniversit� de Strasbourg-CNRS UMR 750423 rue du Loess, BP 43, 67034 Strasbourg (France)Fax: (+33) (0)388107246E-mail : bellemin@unistra.fr

[b] Dr. E. Chardon, Dr. G. GuichardInstitut Europ�en de Chimie et Biologie, Universit� de Bordeaux-CNRS UMR52482 rue Robert Escarpit, 33607 Pessac (France)Fax: (+33) (0)540002200E-mail : g.guichard@iecb.u-bordeaux.fr

Supporting information for this article is available on the WWWunder http://dx.doi.org/10.1002/asia.201201148.

Figure 1. Examples of platinum-NHC complexes exhibiting antitumorproperties.

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compounds. This strategy was thus expanded to the designof a NHC-Pt complex containing a dye pair for fluorescenceresonance energy transfer (FRET).[16]

Results and Discussion

Reactivity and Kinetic Studies

Following the synthetic pathway originally reported bySingh and co-workers,[17] the PtII-(pyridine) complex 2 wassynthesized in 72 % yield from 1-methyl-2-benzylimidazoli-um salt 1 in pyridine as solvent (Scheme 2). The formationof the (NHC)Pt-pyridine complex 2 was established by the

appearance of a signal at d= 136.3 ppm in the 13C NMRspectrum, which was assigned to the carbene carbon and bythe absence of the resonance for the 2H-imidazolium protonin the 1H NMR spectrum. The molecular structure of 2 ob-tained by X-ray diffraction analysis is displayed in Figure 2.As predicted, a square planar geometry around the metalcenter was observed with carbene�platinum and platinum�pyridine bond lengths in accordance with literature values[18]

(1.974(7) and 2.094(6) �, respectively).Pyridine substitution was initially evaluated using very

simple amine models like cyclohexylamine and morpholineto yield the expected products 3 and 4, respectively(Scheme 2).[15] The cyclohexylamine complex 3 was obtained

in quantitative yield (1 h, rt)whereas the morpholine com-plex was obtained in 58 % yieldafter 20 hours at room tempera-ture.

The molecular structure ofthe complexes 3 and 4 in thesolid state could be determinedby X-ray diffraction studies(Figure 3). Selected bondlengths are also presented in

Table 1 for comparison purpose. The complexes both dis-play the coordination of the amine ligand trans to the N-het-erocyclic carbene ligand with the expected square-planar ge-ometry at the platinum center. The two iodide ligands adopta trans geometry (I-Pt-I angle of 176.58 for 3 and 174.38 for

Scheme 1. Non-covalent functionalization of PtII-NHC complexes by ligand substitution.

Scheme 2. Pyridine substitution with cyclohexylamine or morpholine.

Figure 2. Molecular structure of the complex 2. Selected bond lengths(�) and angles (deg): Pt(1)–C(1), 1.974(7); Pt(1)–N(3), 2.094(6); Pt(1)–I(1), 2.5934(5); Pt(1)–I(2), 2.6025(5); C(1)-Pt(1)-I(1), 89.4(2); N(3)-Pt(1)-I(2), 90.4(2); N(2)-C(1)-Pt(1)-I(2), 104.3(6); I(1)-Pt(1)-I(2), 178.40(2);N(1)-C(1)-Pt(1)-I(1), 103.0(6); I(1)-Pt(1)-N(3)-C(16), �57.1(5).

Figure 3. Molecular structures of complexes 3 (a) and 4 (b). Selectedbond lengths (�) and angles (deg), complex 3 : Pt(1)–C(1), 1.964(5);Pt(1)–N(3), 2.121(5); Pt(1)–I(1), 2.6011(5); Pt(1)–I(2), 2.5891(5); I(1)-Pt(1)-C(1), 90.9(2); I(1)-Pt(1)-I(2), 176.54(2); C(1)-Pt(1)-N(3), 178.4(2);I(1)-Pt(1)-N(3), 89.3(1); N(1)-C(1)-Pt(1)-I(1), �85.6(5); complex 4 :Pt(1)–C(1), 1.964(5); Pt(1)–I(1), 2.5968(5); Pt(1)–I(2), 2.6048(5); Pt(1)–N(3), 2.139(4); C(1)-Pt(1)-N(3), 176.0(2); I(1)-Pt(1)-I(2), 174.34(2); I(1)-Pt(1)-C(1), 88.1(2); I(1)-Pt(1)-N(3), 89.5(1); N(1)-C(1)-Pt(1)-I(1),91.0(5).

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4) and point perpendicularly toward the NHC ligand plane[N(1)-C(1)-Pt(1)-I(1), �85.6(5) for 3 and N(1)-C(1)-Pt(1)-I(1), 91.0(5) for 4], a feature that has been observed in allX-ray structures presented here (Table 2 collects the crystal-lographic data). This possibly indicates interactions betweenthe lone pairs of electrons on the iodo ligands and the for-mally antibonding p orbital of the NHC carbon atom. Thisis supported by the C···I(1) and C···I(2) interatomic distan-ces of 3.27 � for 3 and 3.23 � for 4 when compared with thesum of the van der Waals radii for carbon and iodine (~3.68 �).

We performed kinetic studies on the substitution of thepyridine ligand of complex 2 by the morpholine ligand. The1H NMR studies on the formation of the morpholine com-plex 4 demonstrated that the overall order of the reaction is2 with respect to the initial concentrations of complex 2 andmorpholine (vi =k[complex 2][morpholine], k of 42.2�3.0 �10�4 L mol�1 min�1, see the Supporting Information). The

substitution of the pyridine by amines thus may involve anassociative mechanism with a 5-coordinate species as transi-tion state, as usually observed with platinum complexes.[19]

This pyridine/ligand exchange may be obviously facilitatedby the trans effect of the s-donor NHC ligand.[20,21]

Competitive experiments using an equimolar amount ofcyclohexylamine and morpholine in the presence of oneequivalent of pyridine complex 2 were carried out(Scheme 3). After 20 hours at 55 8C, 70 % of the starting ma-terial was consumed, thus giving the corresponding com-plexes 3 and 4 in a 1.5:1 ratio. After 6 days, the ratio be-tween the two products remained unchanged. The first con-clusions that can be drawn include a higher reactivity of pri-mary amines compared to secondary amines, certainly dueto their lower steric hindrance. Accordingly, addition ofexcess of cyclohexylamine to complex 4 resulted in quantita-tive ligand exchange while addition of morpholine to com-plex 3 did not lead to complete conversion (Scheme 4). Al-

Table 1. Pt–carbene and Pt�N bond lengths (�) for complexes 2–4, 10–13, and 17.

2 3 4 9 10 11 12 17

Pt–CNHC [�] 1.974(7) 1.964(5) 1.964(5) 1.971(4) 1.971(6) 1.961(4) 1.957(17) 1.991(4)Pt–N [�] 2.094(6) 2.121(5) 2.139(4) 2.103(4) 2.109(5) 2.098(4) 2.124(19) 2.051(3)

Table 2. Crystallographic data and refinement details for 2–4, 9–12, and 17.

2 3 4 9 10 11 12 17

Empirical for-mula

C16H17I2N3Pt C17H25I2N3Pt C15H21I2N3OPt C18H21I2N3OPt C11H15I2N3Pt C11H15I2N3OPt C17H25I2N3O2Pt C15H25N5Pt,2(I)

M 700.22 720.29 708.24 744.27 638.15 654.15 752.29 724.29T 173(2) K 173(2) K 173(2) K 173(2) K 173(2) K 173(2) K 173(2) K 173(2) Kl (MoKa) 0.71073 � 0.71073 � 0.71073 � 0.71073 � 0.71073 � 0.71073 � 0.71073 � 0.71073 �Crystalsystem

monoclinic monoclinic monoclinic monoclinic triclinic monoclinic triclinic monoclinic

Space group P21/c P21/c P21/c P21/c P�1 P21/c P�1 P21

a [�] 13.4462(2) 10.7415(4) 15.0784(8) 11.4683(4) 12.5423(7) 16.6260(9) 7.9996(3) 11.0718(9)b 8.6778(2) 13.7045(5) 8.9752(5) 22.7334 (9) 14.2898(8) 10.1471(5) 11.5509(7) 8.6604(7)c 16.5739(4) 14.4708(5) 15.1270(8) 8.6865(3) 15.6905(8) 9.6264(5) 12.4003(7) 11.3741(9)a [8] 90.00 90.00 90.00 90.00 81.8980(10) 90.00 91.211(2) 90.00b 102.883(2) 95.928(2) 108.1750(10) 107.0700(10) 68.34030(10) 90.5180(10) 96.270(3) 99.404(2)g 90.00 90.00 90.00 90.00 63.9980(10) 90.00 102.669(3) 90.00U [�3] 1885.22(7) 2118.81(13) 1945.03(18) 2164.92(14) 2349.4(2) 1623.96(15) 1110.03(10) 1075.96(15)Z 4 4 4 4 6 4 2 2Dc [gcm�1] 2.467 2.258 2.419 2.283 2.706 2.676 2.251 2.236m [mm�1] 10.718 9.539 10.393 9.344 12.886 12.436 9.116 9.396F ACHTUNGTRENNUNG(000) 1272 1328 1296 1368 1716 1176 696 668Crystal size[mm]

0.40 � 0.22 � 0.15 0.40 � 0.25 � 0.20 0.35 � 0.30 � 0.20 0.35 � 0.30 � 0.25 0.20 � 0.20 � 0.15 0.25 � 0.20 � 0.15 0.48 � 0.40 � 0.20 0.20 � 0.05 � 0.03

Scan range 1.558 � q �27.498

1.918 � q �27.488

2.688 � q �30.018

2.618 � q �32.068

1.918 � q �30.198

2.458 � q �32.048

1.658 � q �27.528

1.818 � q �29.148

Reflect. col-lected

14630 11603 15 099 21866 37615 21012 11 192 8324

Number ofdata with3 s(I)

4012 4025 4935 6225 11549 4732 4573 4678

Number ofvariables

201 210 204 235 445 173 243 192

R 0.0471 0.0378 0.0342 0.0340 0.0263 0.0284 0.0837 0.0246Rw 0.1200 0.0936 0.0724 0.0585 0.0502 0.0531 0.2109 0.0454GOF 1.135 1.152 1.327 1.149 1.082 1.103 1.294 1.074

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together, these experiments show that ligand exchangefavors the formation of the more thermodynamically stablecompound, with amines having a better Lewis base charac-ter and a lower steric hindrance.

Exploration of Ligand Diversity

We further extended the pyridine substitution with variousstructurally diverse nitrogen-based ligands to generate a li-brary of functionalized PtII-NHC complexes (at 55 8C and inethanol as solvent). A series of compounds (5–9) was thuseasily obtained by exchange with amines, hydrazine, or O-hydroxylamines as shown on Figure 5. These results evi-denced the easy access to various platinum NHC complexes.Noticeably, pyridine substitution with a polyethylene glycolamine gave access to the Pt-complex 5, for which the hydro-solubility could be of particular interest for biomedical ap-plications.[22]

The molecular structure of O-benzylhydroxyamine plati-num complex 9 could be obtained by X-ray diffraction stud-ies as displayed in Figure 4. Complex 9 adopts the typicalsquare planar conformation akin to the previous complexeswith a carbene�platinum and platinum�N bond lengths of1.971(4) � and 2.103(4) �, respectively.

We performed the synthesis of even more diverse struc-tures starting from ammonium salts derived from protectedamino acids or a sorbitol in the presence of a base (typicallyEt3N) to generate in situ the free amino group (compounds10–14, Figure 5). Moreover, reaction with ammonium chlo-ride or hydroxylammonium chloride in the presence of trie-thylamine afforded the corresponding NHC-diiodide com-plexes in reasonable yield. Suitable crystals of complexes 10

and 11 for X-ray analysis were obtained, and the molecularstructures are represented in Figure 6 along with relevantbond lengths and angles. As usual, this arrangement is simi-lar to that found for complex 4.

The tolerance of the substitution reaction to the presenceof functional groups was exemplified by the synthesis ofcomplexes 12–14. The modest yields observed in this seriescould be ascribed to the poor reactivity of the liganditself.[23] Similarly to the previously discussed complexes 4and 10, the molecular structure of complex 12 representedin Figure 7 adopts a square planar coordination at the plati-

Scheme 3. Competitive experiment between cyclohexylamine and mor-pholine in the presence of pyridine complex 2.

Scheme 4. Reversibility of ligand substitution.

Figure 4. Molecular structure of complex 9. Selected bond lengths (�)and angles (deg): C(1)–Pt(1), 1.971(4); N(3)–Pt(1), 2.103(4); I(1)–Pt(1),2.5853(4); I(2)–Pt(1), 2.5940(4); N(3)–O(1), 1.445(5); C(1)-Pt(1)-I(1),89.67(13); I(1)-Pt(1)-I(2), 177.277(16); C(1)-Pt(1)-N(3), 178.66(18); N(3)-Pt(1)-I(1), 89.40(11); N(1)-C(1)-Pt(1)-I(1), �96.7(4).

Figure 5. Ligand substitution on complex 2 with various nitrogen ligands;yields are given in parenthesis.

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num center where the aminoester ligand is N-coordinatedtrans to the carbene. In addition, an intramolecular hydro-gen bond is observed between the hydrogen H(3B) of theamino group and the oxygen O(1) of valine methylester(H(3B)···O(1) distance of 2.35 �).

Dinuclear complexes were also envisioned because theycould further allow the delivery of a higher local concentra-tion of cytotoxic platinum moieties within the cell. The syn-thesis of compound 15 was thus performed starting from l-lysine methyl ester dihydrochloride (0.5 equiv. based on 2)bearing two amino coordination sites (Scheme 5).

By contrast, reaction of ethylenediamine with the Pt-(pyr-idine) complex 2 gave the mononuclear bis-amino coordi-

nated complex 16 owing to the chelating effect of the dia-mine. A hydrosoluble cationic platinum species bearing onlyone iodide ligand was thus generated (Scheme 6).

In a similar way, we also performed the synthesis of com-plex 17 for which mass spectrometry revealed the presenceof at least one coordinated iodide in solution and whosesolid-state molecular structure demonstrated that the diethy-lene triamine can also bind the metal center in a h3 fashionresulting in a distorted square planar coordination geometry(dihedral angle N(2)-C(1)-Pt-N(4) of �988) where the twoiodide ligands have been substituted by the NH2 groups ofdiethylene triamine (Figure 8). The triamine ligand thus ar-ranges in a perpendicular plane with respect to the NHCbackbone. Interestingly, compound 17 crystallizes in thechiral space group P21 with a Flack parameter of 0.49, there-by indicating that the crystal is racemic twinned. Additional-ly, intra- and intermolecular hydrogen bonds between NH,NH2 and the iodide counterions were noticed (H ACHTUNGTRENNUNG(1N4)···I(1)distance of 2.732 � and H ACHTUNGTRENNUNG(2N4)···I(2) distance of 2.764 �;not shown in the figure).

Figure 6. Molecular structures of complexes 10 (a) and 11 (b). Selectedbond lengths (�) and angles (deg), complex 10 : Pt–C(1), 1.971(6); Pt–I(1), 2.6081(3); Pt–I(2), 2.5929(3); Pt–N(3), 2.109(5); C(1)-Pt-N(3),177.9(3); I(1)-Pt-I(2), 177.73(1); I(1)-Pt-C(1), 89.0(1); I(1)-Pt-N(3),89.9(1); N(2)-C(1)-Pt-I(2), �105.0(4); complex 11: C(1)–Pt(1), 1.961(4);N(3)–Pt(1), 2.098(4); I(1)–Pt(1), 2.5929(4); I(2)–Pt(1), 2.5935(4); N(3)–O(1), 1.407(6); C(1)-Pt(1)-I(1), 90.73(13); I(1)-Pt(1)-I(2), 176.783(13);C(1)-Pt(1)-N(3), 178.4(2); N(3)-Pt(1)-I(1), 90.75(16); N(1)-C(1)-Pt(1)–I(1), 84.8(4); intermolecular hydrogen bond O(1)–I(1), 3.450(10).

Figure 7. Molecular structure of complex 12. Selected bond lengths (�)and angles (deg): Pt(1)–C(1), 1.957(17); Pt(1)–I(1), 2.593(1); Pt(1)–I(2),2.592(1); Pt(1)–N(3), 2.124(19); C(16)–O(1), 1.15(7); C(16)–O(2),1.32(4); H(3B)···O(1), 2.35(5); C(1)-Pt(1)-N(3), 173.4(8); I(1)-Pt(1)-I(2),175.63(5); I(1)-Pt(1)-C(1), 87.6(5); I(2)-Pt(1)-N(3), 91.8(6); N(2)-C(1)-Pt(1)-I(2), 101(1); I(1)-Pt(1)-N(3)-C(12), �61(3); Pt(1)-N(3)-C(12)-C(13), �53.4.

Scheme 5. Synthesis of the dinuclear species 15.

Scheme 6. Formation of the cationic platinum complexes 16 and 17 by re-action with ethylenediamine and diethylene triamine, respectively.

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Synthesis of Luminescent Pt-NHC Complexes

Access to platinum NHC complexes exhibiting emissionproperties would be of interest for cell imaging. Indeed, at-tachment of a fluorophore moiety may confer a moleculeemission properties that can be monitored in vitro usingfluorescence microscopy as an imaging mode for biologicalapplications. We have therefore investigated the synthesis ofPtII-NHC derivatives with photophysical properties.[24] Asa representative example, we synthesized the Pt-NHC com-plex 19 having a dansyl substituent 18 coordinated to themetal center via pyridine substitution of complex 2. The de-sired product could be obtained in 70 % yield (Scheme 7).

The absorption and the emission spectra of the platinumcomplex 19 along with the starting material 18 are depictedin Figure 9. The emission spectrum of complex 19 recordedupon excitation at 348 nm showed a distinct and broad fluo-rescent pattern with a maximum of emission at 502 nm.However, it is worth noting that emission intensities of thecomplex are significantly lower when compared to thehighly emissive starting ligand 18.

Attachment of fluorophore moieties on the NHC back-bone at the early stage of the synthesis is another way toconfer emission properties to Pt complexes.[25] We used 1-methyl-3-(9-anthracenylmethyl)imidazolium iodide as a pre-

cursor to synthesize the corresponding NHC-pyridine plati-num complex 20, which was then evaluated by luminescencespectroscopy. Upon UV excitation at the absorption maximaof either 276, 368, or 389 nm, the anthracene Pt complexemits in the 400–470 nm range. Figure 10 also shows that

platinum complexation did not affect the emissive propertiesof the anthracene group as no decrease in emission intensitywas observed when comparing the luminescence spectra of20 with the starting 9-anthrace-nylmethyl chloride.

Since fluorescent labelingmay be easily conducted atboth ends of the Pt-NHC mole-cule, it is therefore possible toincorporate a dye pair for fluo-rescence resonance energy

Figure 8. Molecular structure of the dicationic complex 17. Selected bondlengths (�) and angles (deg): Pt(1)–C(1), 1.991(4); Pt(1)–N(3), 2.051(3);Pt(1)–N(4), 2.10(1); Pt(1)–N(5), 1.98(2); C(1)-Pt(1)-N(5), 94.0(6); N(5)-Pt(1)-N(3), 84.7(5); N(4)-Pt(1)-N(3), 84.6(7); N(2)-C(1)-Pt(1)-N(4),�98(1); N(4)-Pt(1)-N(3)-N(5), 176.9(7).

Scheme 7. Synthesis of Pt-NHC dansyl derivative 19.

Figure 9. Absorption (dashed lines) and emission (solid lines) spectra ofcompounds 18 (F=0.39�0.10) and 19 (F=0.04�0.01) in dichlorome-thane at 298 K. Emission spectra were recorded upon excitation at344 nm.

Figure 10. Absorption (dashed lines) and emission (solid lines) spectra ofcompounds 20 and 9-anthracenylmethyl chloride in dichloromethane (c =

1.34 � 10�4m) at 298 K. Emission spectra were recorded upon excitation

at 368 nm.

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transfer (FRET).[16] Such systems would be of particular in-terest to gain insights into the mode of action of these mole-cules in vitro. FRET spectroscopy would permit to localizeand provide evidence of the active intermediate within thecell, that is, to follow the ligand substitution reaction. FRETinvolves a donor fluorophore in an excited electronic state,which may transfer its excitation energy to a close acceptorchromophore in a non-radiative manner through long-rangedipole–dipole interactions. Energy transfer occurs when theexcited fluorophore dipole and the close acceptor dipolehave similar resonance frequencies, which implies that theemission wavelength of the donor overlaps the excitationwavelength of the acceptor. As proof of concept, we havedesigned the NHC-platinum complex 22, combining an an-thracene group on the NHC backbone and a dabsyl deriva-tive as a nitrogen-based ligand located trans to the carbene.Complex 22 was obtained through pyridine ligand exchangefrom the reaction of the anthracene Pt complex 20 anddabsyl derivative 21 in 70 % yield (Scheme 8). The absorp-

tion spectrum of complex 22 (Figure 11) shows intensebands in the regions 250–300 nm and 350–400 nm that arespecific of the anthracene moiety. The broad band at 400–500 nm is specific of the dabsyl moiety and thus may beused as a dark quencher of the excitation energy of the an-thracene moiety. Upon excitation of the anthracene at368 nm, the fluorophore�s emission is suppressed(Figure 11), which confirmed that the anthracene emission isquenched by the dabsyl group. We envisioned that the lumi-nescent properties of the anthracene moiety may be recov-ered upon the release of the dabsyl quencher from the plati-num complex (i.e. , ligand exchange of the dark quenchertrans to the carbene). As expected, the emission of the plati-num complex was shown to switch on, for instance, in thepresence of cyclohexylamine (Figure 12). This highlights thegreat potential of this complex to study, for example, the in-teraction of NHC platinum complexes with DNA.

Scheme 8. Synthesis of Pt-NHC dabsyl derivative 22.

Figure 11. Absorption and emission spectra of compound 22 (c =1.34 �10�4

m, 298 K) upon excitation at 368 nm .

Figure 12. Emission spectra of compound 22 (c =10�4m in dichlorome-

thane) upon excitation at 368 nm in the presence of cyclohexylamine(10 equiv) as a function of time at room temperature; t= 0, 3, 6, 7, 8, 9,21 and 32 h.

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Conclusions

We have demonstrated herein the feasibility and versatilityof a method for functionalization of platinum NHC com-plexes by means of pyridine substitution. In this work, theligand substitution proved to be highly selective toward thecoordination of amino groups. Encouraged by these results,we extended the scope of this modular and easy-to-handlemethod to a more diverse set of amines, from amino-substi-tuted polyethylene glycol to hydrazine and hydroxylaminederivatives. We also synthesized cationic platinum moietiesusing di- and triamines. Altogether, these examples highlightthat the post-functionalization of NHC complexes of plati-num represents a method of choice for the generation ofchemical libraries of cytotoxic complexes whose biologicalfeatures could be easily tuned according to the introducedamino moiety.

We also have presented a luminescent platinum(II) com-plex in which the emission is switched on upon ligand ex-change. Such complexes may be an interesting tool to betterunderstand the interaction of NHC platinum(II) complexeswith DNA. This could form the basis of further studieswhich are worth exploring in the near future.

Experimental Section

General Considerations

All reactions were performed under an inert atmosphere of argon or ni-trogen using standard Schlenk line techniques. Solvents were purifiedand degassed by standard procedures. All other reagents were used with-out further purification. 1H and 13C NMR spectra were recorded ona Bruker AVANCE 300 spectrometer using the residual solvent peak asreference (CDCl3: dH =7.26 ppm; dC = 77.16 ppm) at 298 K. High-resolu-tion mass spectrometry (HRMS) analyses were performed in the ESImode using a microTOF instrument (Bruker Daltonics). Crystal datawere collected at 173 K using a MoKa graphite monochromated (l=

0.71073 �) radiation on a Nonius KappaCCD diffractometer. The struc-tures were solved using direct methods with SHELXS97. Non-hydrogenatoms were refined anisotropically. Hydrogen atoms were generated ac-cording to stereochemistry and refined using a riding model inSHELXL97. UV/Vis absorption spectra were recorded on a Hitachi U-3000 spectrophotometer, and fluorescence spectra were obtained ona MD-5020 fluorimeter (Photon Technology International). Lumines-cence quantum yields were referenced to quinine sulfate dehydrate in0.1m aqueous H2SO4 (fref =0.54). The synthesis of complexes 2–4 and 7has been previously reported.[15] Literature procedures were followed toprepare compounds 1,[15] 18,[26] and 21.[27] CCDC 911923 (4), 911924 (12),911925 (9), 911926 (11), 911927 (2), 911928 (10), 911929 (17), and 911930(3) contain the supplementary crystallographic data for this paper. Thesedata can be obtained free of charge from The Cambridge Crystallograph-ic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.

Synthesis of Trans-[(NHC)PtI2(methoxy-polyethylene glycol amine)] (5)

Methoxy-polyethylene glycol amine (61 mg, 0.046 mmol, PEG MW =

750 Da) was added to a suspension of trans-[(NHC)PtI2 ACHTUNGTRENNUNG(pyridine)] 2(32 mg, 0.046 mmol) in ethanol (2 mL). The solution was stirred for 20 hat 55 8C, concentrated under reduced pressure, washed with pentane, andpurified by silica gel chromatography (CH2Cl2/MeOH 10:1) to afford 5 asa yellow oil (30 mg, 45 %). 1H NMR (CDCl3, 300 MHz, 20 8C): d=2.05 (s,2H, NH2), 3.18 (m, 4H, 2CH2), 3.37 (s, 3H, OCH3), 3.40–3.79 (m, ~80 H,40CH2), 3.87 (s, 3H, NCH3), 5.60 (s, 2 H, NCH2), 6.60 (d, 1 H, CH), 6.80(d, 1 H, CH), 7.25–7.60 ppm (m, 5H, 5Ar-H); 13C NMR (CDCl3, 75 MHz,

20 8C): d =38.1 (NCH3), 45.1 (NH2CH2), 54.4 (NCH2), 59.0 (OCH3), 70.2(CH2), 70.5 (CH2), 71.9 (CH2), 119.8 (CH), 122.2 (CH), 128.2 (CHar),128.8 (CHar), 129.0 (CHar), 135.4 Car), 141.2 ppm (C-Pt); HRMS (positiveESI) [M+Na] calcd for C46H84I2N3O17PtNa, found 1423.364.

Synthesis of Trans-[(NHC)PtI2(l-prolinol)] (6)

l-Prolinol (13 mL, 0.131 mmol) was added to a suspension of trans-[(NHC)PtI2 ACHTUNGTRENNUNG(pyridine)] 2 (31 mg, 0.044 mmol) in ethanol (2 mL). The so-lution was stirred for 24 h at 55 8C, concentrated under reduced pressure,washed with pentane, and purified by silica gel chromatography (CH2Cl2,then CH2Cl2/MeOH 20:1) to afford 6 as a yellow oil (28 mg, 90%).1H NMR (CDCl3, 300 MHz, 20 8C): d=1.73–1.86 (m, 4 H, 2CH2), 2.36 (t,J =6.1 Hz, 1H, OH), 3.12 (m, 1 H, NH), 3.24–3.68 (m, 4H, 2CH2), 3.89 (s,3H, N-CH3), 4.45 (m, 1H, CH), 5.58 (s, 2H, CH2), 6.57 (d, J =2.1 Hz,1H), 6.79 (d, J =2.1 Hz, 1H), 7.32–7.46 ppm (m, 5H, 5Ar-H); 13C NMR(CDCl3, 75 MHz, 20 8C): d =25.1 (CH2), 26.4 (CH2), 38.3 (NCH3), 52.1(CH2), 54.6 (NCH2), 60.3 (CH), 65.8 (CH2), 120.2 (CH), 122.5 (CH),128.6 (CHar), 129.0 (CHar), 129.2 (CHar), 135.5 (Car), 139.3 ppm (C-Pt);HRMS (positive ESI) [M+Na] calcd for C16H23I2N3PtONa: 744.947,found 744.960; elemental anal. calcd (%) for C16H23I2N3OPt: C 26.61, H3.21, N 5.82; found: C 26.77, H 3.47, N 5.61.

Synthesis of Trans-[(NHC)PtI2(O-methylhydroxyamine)] (8)

A mixture of trans-[(NHC)PtI2ACHTUNGTRENNUNG(pyridine)] 2 (20 mg, 28.6 mmol), O-meth-ylhydroxylammonium chloride (24 mg, 287.4 mmol), and triethylamine(80 mL, 573 mmol) in THF (3 mL) was stirred overnight at 55 8C. The mix-ture was concentrated under reduced pressure, filtered through a Celiteplug with CH2Cl2, concentrated under reduced pressure, washed withpentane, and purified by chromatography on silica gel (cyclohexane/CH2Cl2 1:1) to afford 8 as a yellow solid (7.6 mg, 39 %). 1H NMR(CDCl3, 300 MHz, 20 8C): d =3.90 (s, 3H, O-CH3), 3.93 (s, 3 H, N-CH3),5.58 (s, 2 H, N-CH2), 6.43 (m, 2H, NH2), 6.59 (d, J= 2.2 Hz, 1H, CHim),6.81 (d, J =2.2 Hz, 1 H, CHim), 7.27–7.49 ppm (m, 5 H, CHar); 13C NMR(CDCl3, 75 MHz, 20 8C): d =38.2 (N-CH3), 54.4 (N-CH2), 63.8 (O-CH3),120.1 (CHim), 122.5 (CHim), 128.4 128.8 129.0 (CHar), 135.1 (Car),137. ppm (C-Pt); MS (positive ESI) [M +Na]: calculated forC12H17I2N3O1Pt1Na1: 690.90, found 690.90, [M�I-NH2OMe]: calculatedfor C11H12I1N2Pt1: 493.97, found 493.97, [M�I]: calculated forC12H17I1N3O1Pt1: 541.01, found 541.00.

Synthesis of Trans-[(NHC)PtI2(O-benzylhydroxylamine)] (9)

A mixture of trans-[(NHC)PtI2 ACHTUNGTRENNUNG(pyridine)] 2 (30 mg, 42.8 mmol), O-ben-zylhydroxylammonium chloride (68.4 mg, 429 mmol), and triethylamine(120 mL, 889 mmol) in THF (3 mL) was stirred overnight at 55 8C. Themixture was concentrated under reduced pressure, filtered througha Celite plug with CH2Cl2, concentrated under reduced pressure, washedwith pentane, and purified by chromatography on silica gel (cyclohexane/CH2Cl2 1:1) to afford 9 as a yellow solid (25.1 mg, 76%). 1H NMR(CDCl3, 300 MHz, 20 8C): d =3.90 (s, 3H, N-CH3), 5.17 (s, 2H, O-CH2),5.59 (s, 2 H, N-CH2), 6.34 (m, 2H, NH2), 6.59 (d, J= 2.1 Hz, 1H, CHim),6.81 (d, J=2.1 Hz, 1 H, CHim), 7.27–7.52 ppm (m, 10 H, CHar); 13C NMR(CDCl3, 75 MHz, 20 8C): d =38.2 (N-CH3), 54.5 (N-CH2), 77.1 (O-CH2),120.1 (CHim) 122.4 (CHim), 128.3 128.4 128.6 128.9 129.1 129.3 133.8135.2 ppm (Car). MS (positive ESI) [M�I]: calculated forC18H21I1N3O1Pt1: 617.04, found 617.04, [M�I+CH3CN]: calculated forC18H21I1N3O1Pt1CH3CN: 658.06, found 658.07, [M+ Na]: calculated forC18H21I2N3O1Pt1Na1: 766.93, found 766.93.

Synthesis of Trans-[(NHC)PtI2 ACHTUNGTRENNUNG(ammonia)] (10)

Ammonium chloride (9 mg, 0.168 mmol) and triethylamine (20 mL,0.148 mmol) were added to a suspension of trans-[(NHC)PtI2ACHTUNGTRENNUNG(pyridine)]2 (28 mg, 0.040 mmol) in ethanol (1 mL). The solution was stirred for24 h at 55 8C, concentrated under reduced pressure, washed with pentane,and purified by silica gel chromatography (CH2Cl2/cyclohexane 3:1) toafford 10 as a yellow solid (12 mg, 48 %). Spectroscopic data were consis-tent with previously reported data for this compound.[12b]

Chem. Asian J. 2013, 8, 1232 – 1242 � 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim1239

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Synthesis of Trans-[(NHC)PtI2(hydroxylamine)] (11)

A mixture of trans-[(NHC)PtI2ACHTUNGTRENNUNG(pyridine)] 2 (20 mg, 28.6 mmol), hydroxy-lammonium chloride (20 mg, 288 mmol), and triethylamine (77 mL,571 mmol) in THF (3 mL) was stirred overnight at 55 8C. The mixture wasconcentrated under reduced pressure, filtered through a Celite plug withCH2Cl2, concentrated under reduced pressure, washed with pentane, andpurified by chromatography on silica gel (cyclohexane/CH2Cl2 1:1) toafford 11 as a yellow solid (9.3 mg, 49%).1H NMR (CDCl3, 300 MHz,20 8C): d =3.89 (s, 3H, N-CH3), 5.56 (s, 2H, N-CH2), 5.83 (t, J=3.5, 1H,OH), 5.98 (m, 2 H, NH2), 6.62 (d, J =2.1 Hz, 1H, CHim), 6.83 (d, J=

2.1 Hz, 1 H, CHim), 7.27–7.48 ppm (m, 5 H, CHar); 13C NMR (CDCl3,75 MHz, 20 8C): d=38.3 (N-CH3), 54.5 (N-CH2), 120.3 (CHim), 122.6(CHim), 128.4 128.8 128.9 (CHar), 135.0 (Car), 135.8 ppm (C-Pt); MS (posi-tive ESI) [M +Na]: calculated for C11H15I2N3O1Pt1Na1: 676.88, found676.89, [M�I+CH3CN]: calculated for C11H15I1N3O1Pt1CH3CN: 568.02,found 568.01, [M�I]: calculated for C11H15I1N3O1Pt1: 526.99, found526.99.

Synthesis of Trans-[(NHC)PtI2(l-valine methyl ester)] (12)

l-Valine methyl ester hydrochloride (16 mg, 0.093 mmol) and triethyla-mine (21 mL, 0.150 mmol) were added to a suspension of trans-[(NHC)PtI2 ACHTUNGTRENNUNG(pyridine)] 2 (54 mg, 0.077 mmol) in ethanol (6 mL). The so-lution was stirred for 24 h at 75 8C, concentrated under reduced pressure,washed with pentane, and purified by silica gel chromatography (CH2Cl2/cyclohexane 2:1) to afford 12 as a yellow solid (34 mg, 59 %). 1H NMR(CDCl3, 300 MHz, 20 8C): d =1.09 (d, J= 7.2 Hz, 6 H, 2CH3), 2.60 (m,1H, CH), 3.42 (m, 2H, NH2), 3.78 (s, 3H, CH3), 3.88 (s, 3 H, CH3), 4.23(m, 1H, CH), 5.57 (s, 2 H, NCH2), 6.57 (s, 1 H, CH), 6.78 (s, 1H, CH),7.34–7.46 ppm (m, 5H, 5Ar-H); 13C NMR (CDCl3, 75 MHz, 20 8C): d=

17.9 (CH3), 18.8 (CH3), 29.7 (CH), 38.2 (N-CH3), 52.4 (OCH3), 54.4(NCH2), 63.7 (CH), 120.0 (CH), 122.3 (CH), 128.2 (CHar), 128.5 (CHar),128.9 (CHar), 135.3 (Car), 137.5 (C-Pt), 172.8 ppm (CO); HRMS (positiveESI) [M +Na]: calcd for C17H25I2N3PtO2.Na 744.947, found 744.960; ele-mental anal. calcd (%) for C17H25I2N3O2Pt: C 27.14, H 3.35, N 5.59;found: C 26.97, H 3.40, N 5.51.

Synthesis of Trans-[(NHC)PtI2(methyl 6-aminohexanoate)] (13)

Methyl 6-aminohexanoate (13 mg, 0.090 mmol) was added to a suspensionof trans-[(NHC)PtI2 ACHTUNGTRENNUNG(pyridine)] 2 (20 mg, 0.029 mmol) in ethanol (2 mL).The solution was stirred for 20 h at 55 8C, concentrated under reducedpressure, washed with pentane, and purified by silica gel chromatography(CH2Cl2, then CH2Cl2/MeOH 20:1) to afford 13 as a yellow oil (10 mg,45%). 1H NMR (CDCl3, 300 MHz, 20 8C): d=1.26 (m, 2H, CH2), 1.66(m, 4 H, 2CH2), 2.33 (t, J =7.2 Hz, 2 H, CH2), 3.04 (m, 4 H, CH2 andNH2), 3.66 (s, 3H, OCH3), 3.89 (s, 3 H, NCH3), 5.59 (s, 2H, NCH2), 6.57(d, J=2.1 Hz, 1 H, CH), 6.78 (d, J =2.1 Hz, 1H, CH), 7.32–7.46 ppm (m,5H, 5Ar-H); 13C NMR (CDCl3, 75 MHz, 20 8C): d=24.4 (CH2), 26.0(CH2), 31.7 (CH2), 33.8 (CH2), 38.2 (NCH3), 45.3 (CH2), 51.5 (OCH3),54.4 (NCH2), 119.9 (CH), 122.2 (CH), 128.3 (CHar), 128.8 (CHar), 129.2(CHar), 135.4 (Car), 139.4 (C-Pt), 173.8 ppm (CO); HRMS (positive ESI)[M+ Na]: calcd for C18H27N3I2O2Pt.Na 788.973, found 788.973; elementalanal. calcd (%) for C18H27I2N3O2Pt: C 28.21, H 3.55, N 5.48; found: C27.99, H 3.36, N 5.56.

Synthesis of Trans-[(NHC)PtI2(d-glucamine)] (14)

d-Glucamine (6 mg, 0.034 mmol) was added to a suspension of trans-[(NHC)PtI2 ACHTUNGTRENNUNG(pyridine)] 2 (18 mg, 0.026 mmol) in ethanol (1 mL). The so-lution was stirred for 20 h at 55 8C, concentrated under reduced pressure,washed with pentane, and purified by silica gel chromatography (CH2Cl2,then CH2Cl2/MeOH 10:1) to afford the complex 14 as a yellow oil (8 mg,38%). 1H NMR (CDCl3, 300 MHz, 20 8C): d=1.99 (m, 4 H, 4OH), 3.15(m, 2H, NH2), 3.40 (m, 1H, CH), 3.51–4.45 (m, 8H, 2CH2, 4CH), 3.84 (s,3H, NCH3), 5.56 (s, 2H, NCH2), 6.48 (s, 1H, CH), 6.71 (s, 1H, CH),7.29–7.43 ppm (m, 5 H, 5Ar-H); HRMS (positive ESI) [M +Na]: calcd forC17H27I2N3O5PtNa 824.958, found 824.956.

Synthesis of Lysine Derivative 15

H-Lys-OMe dihydrochloride (7 mg, 0.029 mmol) and triethylamine(50 mL, 0.370 mmol) were added to a suspension of trans-[(NHC)PtI2ACHTUNGTRENNUNG(pyridine)] 2 (40 mg, 0.057 mmol) in THF (2 mL). The solution wasstirred for 24 h at 55 8C, concentrated under reduced pressure, washedwith pentane, and purified by silica gel chromatography (CH2Cl2/cyclo-hexane 2:1, then CH2Cl2) to afford 15 as a yellow oil (15 mg, 33%).1H NMR (CDCl3, 300 MHz, 20 8C): d=1.62–1.81 (m, 4 H, 2CH2), 1.98–2.34 (m, 2 H, CH2), 2.78–3.10 (m, 4 H, 2NH2), 3.46 (m, 2H, CH2), 3.79 (s,3H, OCH3), 3.86 (s, 6H, 2NCH3), 4.30 (m, 1 H, CH), 5.59 (s, 4H,2NCH2), 6.57 (m, 2 H, 2CH), 6.78 (m, 2 H, 2CH), 7.34–7.46 ppm (m, 10H,10Ar-H); MS (positive ESI) [M +Na]: calcd for C29H40I4N6O2Pt2.Na1424.86, found 1424.85.

Synthesis of [(NHC)PtI(ethylenediamine)] iodide (16).

Ethylenediamine (10 mL, 0.143 mmol) was added to a suspension oftrans-[(NHC)PtI2 ACHTUNGTRENNUNG(pyridine)] 2 (20 mg, 0.029 mmol) in ethanol (1.5 mL).The solution was stirred for 20 h at 55 8C, concentrated under reducedpressure, and washed with CH2Cl2 and pentane to afford 16 as a whitesolid (10 mg, 50 %). 1H NMR (CD3OD, 300 MHz, 20 8C): d=2.20–2.60(m, 4 H, 2CH2), 3.94 (s, 3H, NCH3), 5.36 and 5.84 (2d: AB system, J=

14.7 Hz, 2� 1H, NCH2), 7.04 (d, J=2.1 Hz, 1 H, CH), 7.20 (d, J =2.1 Hz,1H, CH), 7.37–7.47 ppm (m, 5H, 5Ar-H); MS (positive ESI) [M+]: calcdfor C13H20IN4Pt 554.038, found 554.040; elemental anal. calcd (%) forC13H20I2N4Pt: C 22.92, H 2.96, N 8.22; found: C 22.86, H 3.08, N 8.39.

Synthesis of [(NHC)PtI(diethylenetriamine)] iodide (17)

Diethylenediamine (8 mL, 0.072 mmol) was added to a suspension oftrans-[(NHC)PtI2 ACHTUNGTRENNUNG(pyridine)] 2 (10 mg, 0.014 mmol) in ethanol (2 mL).The solution was stirred for 3 h at 55 8C, concentrated under reducedpressure, and washed with CH2Cl2 and THF to afford the 17 as a whitesolid (6 mg, 60%). 1H NMR (CD3CN, 300 MHz, 20 8C): d=2.50–3.20 (m,8H, 4CH2), 3.55–3.86 (m, 2 H, NH2), 3.95 and 4.03 (s, 3H, NCH3), 5.55 (s,2H, NCH2), 7.00–7.61 ppm (m, 7 H, 5Ar-H and 2CH); 13C NMR([D6]DMSO, 75 MHz, 20 8C): d=38.0 (NCH3), 38.1 (NCH3), 51.3(NCH2), 51.5 (NCH2), 51.6 (NCH2), 51.8 (NCH2), 53.7 (NCH2), 54.0(NCH2), 122.0 (CH), 124.0 (CH), 128.7 (CHar), 129.1 (CHar), 129.3(CHar), 129.4 (CHar), 136.7 (Car), 137.1 (Car), 149.6 (C-Pt), 149.9 ppm (C-Pt); HRMS (positive ESI, -H2O/CH3CN) [M�I]: calculated forC15H25N5IPt 597.080, found 597.078.

Synthesis of [(NHC)PtI2(piperazinyl-dansyl)] (19)

N,N-Dimethyl-5-(piperazin-1-ylsulfonyl)naphthalen-1-amine 18 (18 mg,0.056 mmol) was added to a suspension of trans-[(NHC)PtI2ACHTUNGTRENNUNG(pyridine)] 2(30 mg, 0.043 mmol) in ethanol (2 mL). The solution was stirred for 24 hat 55 8C, concentrated under reduced pressure, washed with pentane, andpurified by silica gel chromatography (CH2Cl2) to afford 19 as a yellowoil (28 mg, 70%). 1H NMR (CDCl3, 300 MHz, 20 8C): d= 2.61 (m, 2H,2CH), 2.90 (s, 6 H, 2CH3), 3.04 (m, 2 H, 2CH), 3.45 (m, 2H, 2CH), 3.73(m, 2 H, 2CH), 3.82 (s, 3 H, NCH3), 5.51 (s, 2H, NCH2), 6.54 (d, J=

2.1 Hz, 1H, CH), 6.76 (d, J= 2.1 Hz, 1 H, CH), 7.21 (d, J =7.5 Hz, 1H,CHar), 7.35 (m, 5H, 5Ar-H), 7.56 (dd, J=8.7 and 15.9 Hz, 2 H, 2CHar),8.19 (d, J =7.2 Hz, 1H, CHar), 8.37 (d, J =8.7 Hz, 1H, CHar), 8.60 ppm (d,J =8.4 Hz, 1H, CHar); 13C NMR (CDCl3, 75 MHz, 20 8C): d=38.2(NCH3), 45.4 [N ACHTUNGTRENNUNG(CH3)2], 47.0 (CH2), 49.3 (CH2), 54.5 (NCH2), 115.6(CHar), 119.4 (CHar), 120.0 (CHar), 122.3 (CH), 123.1 (CH), 128.3, 128.5,128.8, 129.0, 130.2, 130.4, 130.9, 131.2, 131.8 (C-SO2), 135.2 (C-Pt),151.9 ppm (C-N); HRMS (positive ESI) [M+H]: calculated forC27H33I2N5O2PtS 941.017, found 941.016; UV/Vis (CH2Cl2) lmax (nm) (e,m�1 cm�1): 257 (21 330), 344 (4030); luminescent properties: lexc =344 nm;

lem =450–550 nm; f= 0.04�0.01.

Synthesis of Trans-[(NHCanthracene)PtI2ACHTUNGTRENNUNG(pyridine)] (20)

A mixture of 3-(anthracen-9-ylmethyl)-1-methyl-1H-imidazol-3-iumiodide[28] (35 mg, 0.087 mmol), platinum chloride (26 mg, 0.096 mmol),sodium iodide (130 mg, 0.167 mmol), and potassium carbonate (121 mg,0.874 mmol) was suspended in pyridine (10 mL). The mixture was soni-cated and then stirred at 100 8C for 24 h. The resulting suspension was

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concentrated under reduced pressure, then dissolved in CH2Cl2, filteredthrough a Celite plug, concentrated under reduced pressure, and purifiedby chromatography on silica gel (CH2Cl2/cyclohexane 2:1) to afford 20 asa yellow solid (22 mg, 31 %). 1H NMR (CDCl3, 300 MHz, 20 8C): d=4.04(s, 3 H, CH3), 5.98 (d, J =2.1 Hz, 1 H, CH), 6.58 (s, 2 H, NCH2), 6.60 (d,J =1.8 Hz, 1H, CH), 7.39 (m, 2H, 2CHpyridine), 7.55 (m, 4H, 4CHanthracenyl),7.77 (m, 1 H, CHpyridine), 8.09 (d, J =7.8 Hz, 2H, 2CHanthracenyl), 8.46 (d, J =

5.7 Hz, 2H, 2CHanthracenyl), 8.59 (s, 1H, CHanthracenyl), 9.18 ppm (m, 2 H,2CHpyridine); HRMS (positive ESI) [M�I]: calculated for C24H21IN3Pt673.043, found 673.045; UV/Vis (CH2Cl2) lmax (nm) (e, m

�1 cm�1): 276(9480), 334 (3490), 351 (5930), 368 (8890), 389 (8230); luminescent prop-erties: lexc =368 nm; lem =400–470 nm.

Synthesis of [(NHC)PtI2(piperazinyl-dabsyl)] (22)

N,N-dimethyl-4-[2-[4-(1-piperazinylsulfonyl) phenyl]diazenyl]-benzena-mine 21 (12 mg, 0.033 mmol) was added to a suspension of trans-[(NHC)PtI2 ACHTUNGTRENNUNG(pyridine)] 20 (22 mg, 0.027 mmol) in ethanol (1 mL). The so-lution was stirred for 24 h at 55 8C, concentrated under reduced pressure,washed with pentane, and purified by silica gel chromatography (CH2Cl2)to afford 22 as a red powder (21 mg, 70%). 1H NMR (CDCl3, 300 MHz,20 8C): d =2.42 (m, 2H, CH2), 3.14 (s, 6 H, N ACHTUNGTRENNUNG(CH3)2), 3.21 (m, 2H, CH2),3.67 (m, 2H, CH2), 3.79 (m, 2 H, CH2), 3.87 (s, 3 H, N-CH3), 5.92 (d, J=

2.1, 1 H), 6.37 (s, 2 H, N-CH2), 6.53 (d, J =2.1, 1 H), 6.78 (d, J =9.3, 2 H,CHdabsyl), 7.55 (m, 4H, CHanthr.), 7.93 (m, 6H, CHdabsyl), 8.05 (d, J =7.8,2H, CHanthr.), 8.35 (d, J= 9.0, 2H, CHanthr.), 8.56 ppm (s, 1H, CHanthr.) ;13C NMR (CDCl3, 75 MHz, 20 8C): d=38.5 (NCH3), 40.5 [N ACHTUNGTRENNUNG(CH3)2], 47.8(CH2 (dabsyl)), 48.0 (CH2), 49.5 (CH2 (dabsyl)), 111.7, 119.9 (CHim), 121.4(CHim), 123.0, 124.5, 125.5 (C9anthr.), 125.7, 126.1, 127.6, 129.0, 129.3,129.7, 131.5, 131.7, 134.7, 138.2 (C-Pt), 143.9, 153.4, 155.9 ppm: HRMS(positive ESI) [M +H]: calculated for C37H40I2N7O2PtS: 1095.070, found1095.068; UV/Vis (CH2Cl2) lmax (nm) (e, m

�1 cm�1): 276 (6080), 334(1580), 351 (2340), 368 (3800), 389 (5400), 447 (8840).

Acknowledgements

The authors gratefully acknowledge the CNRS (France) and the Minis-t�re de l’Enseignement Sup�rieur et de la Recherche (MESR) for a PhDgrant to E.C. This work was supported by La Ligue contre le Cancer—R�gion Grand Est. The authors also thank Dr. C. Bailly and Dr. L.Brelot for X-ray diffraction studies (Strasbourg).

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Received: December 1, 2012Revised: February 14, 2013

Published online: April 4, 2013

Chem. Asian J. 2013, 8, 1232 – 1242 � 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim1242

www.chemasianj.org St�phane Bellemin-Laponnaz et al.