Azido-Adamantyl Tin Sulfide Clusters for Bioconjugation

Article Cite This: Organometallics XXXX, XXX, XXX−XXX

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Azido-Adamantyl Tin Sulfide Clusters for Bioconjugation Jan-Philipp Berndt,†,‡ Annikka Engel,§ Radim Hrdina,†,‡ Stefanie Dehnen,*,§ and Peter R. Schreiner*,†,‡ †

Institute of Organic Chemistry and ‡Laboratory of Materials Research (LaMa), Justus Liebig University, 35392 Giessen, Germany § Department of Chemistry and Wissenschaftliches Zentrum für Materialwissenschaften (WZMW), Philipps-Universität Marburg, Hans-Meerwein-Straße 4, 35037 Marburg, Germany

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S Supporting Information *

ABSTRACT: We present a new versatile route toward biomoleculefunctionalized tin sulfide clusters. A novel bifunctional orthogonal spacer was developed and used for the formation of a trifold azido-adamantylterminated cluster, serving as a building block for click reactions. The azido cluster was quantitatively bioconjugated via a strain-promoted 1,3-dipolar cycloaddition, affording a peptide-decorated cluster.

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INTRODUCTION The sensitivity of many organometallic compounds toward air and moisture makes their application as drugs rather counterintuitive. Still, there is a variety of metal-based therapeutic agents for medicinal applications.1 Platinum complexes are essential in the field of cancer chemotherapy.1e,2 Ferrocene derivatives display a broad range of biomedical activities as anticonvulsant, antimalarial, antioxidant, and antitumor agents.3 Gold compounds are used for treatment of rheumatoid arthritis,4 and organotin compounds show great potential in anticancer therapy.5 Furthermore, organotin compounds also possess biocidal properties and are used as antifouling agents,6 fungicides, acaricides, and antimicrobials.7 The multifaceted applications of metal compounds result from their vast structural diversity. Coordination modes can vary from two to ten, thus providing access to a large variety of structural entities. Moreover, ligand design allows fine-tuning of properties such as reactivity, solubility, hydrolytic stability, and in the case of drugs, specificity for target recognition and absorption.1b On the basis of our experience in functionalization of tin chalcogenides,8 we showed that the aggregation level and hence composition and structures of tin sulfide clusters can be controlled by introducing highly rigid organic ligands.9 The embedding of chalcogenide clusters into organic shells facilitates the property tuning, affects solubility, enhances stability, and enables further postfunctionalization.8e,10 Recently, we demonstrated the functionalization of tin chalcogenide clusters with amino acids and oligopeptides.11 The logical extension of this work is the design of ligands enabling control of the aggregation level as well as © XXXX American Chemical Society

postfunctionalization with biomolecules, such as peptides, consequently affecting biocompatibility and bioactivity of the clusters. Cell-penetrating peptides (CPPs) are well-known as cellular delivery agents and facilitate the transport of a variety of therapeutic agents,12 polymers,13 and nanoparticles14 into cells.15 The attachment of such biomolecules may permit the specific delivery of polar and potentially hydrolyzable tin chalcogenide moieties into cells, allowing their targeted use as inhibitors or cytotoxic agents. The functionalization of keto-terminated tin sulfide clusters with hydrazides via hydrazone formation is well-known.8a−h However, there are still challenges to be met for an efficient functionalization of these clusters, e.g., yields are often low due to isolation or stability issues and cross-reactivities with amines are observed. Inspired by previous reports on bioconjugations, we envisioned a modular approach for the functionalization of chalcogenide clusters to be an efficient and versatile route to prepare biomolecule-functionalized clusters.16 These reactions have to meet certain criteria, such as no cross-reactivity with any natural functional group (bioorthogonality), fast reaction rates, and high yields, ideal requirements for the functionalization of chalcogenides. Polyoxometalates (POMs) and nanoparticle materials can be assembled via Huisgen 1,3-dipolar cycloadditions, peptide and related bond formations, and Sonogashira or Heck cross-coupling reactions.17 However, to the best of our knowledge, the previously mentioned reactions have never been applied for the functionalization of tin sulfide clusters. Such a modular approach requires the design of a Received: October 9, 2018

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DOI: 10.1021/acs.organomet.8b00734 Organometallics XXXX, XXX, XXX−XXX

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Organometallics Scheme 1. Modular Approach toward Biomolecule-Functionalized Tin Sulfide Clusters

Scheme 2. Synthesis and Molecular Structure of 2a

a (A) Synthesis of 3-azido-adamantanecarboxylic acid hydrazide 2. (B) Molecular structure of an H-bonded dimer of compound 2. Ellipsoids are drawn at 50% probability. Nonrelevant hydrogen atoms are omitted for clarity. Ranges of selected bond length [Å]: N1−N2 1.419(3), N6−N7 1.420(3), C1−O1 1.235(3), C12−O2 1.232(3), N3−N4 1.229(4), N4−N5 1.137(4), N8−N9 1.229(3), N9−N10 1.130(4), C1−N1 1.342(3), C12−N7 1.343(3), O2−H2B 2.1250(16), O1−H6A 2.139(2).

3-azido-adamantanecarboxylic acid hydrazide 2, in 45% overall yield over seven steps. Slow evaporation of a solution of 3azido-adamantanecarboxylic acid hydrazide 2 (R1) in deuterated chloroform afforded colorless crystals (Scheme. 2B). The compound crystallizes in the monoclinic space group P21 (Z = 4). In the unit cell, two molecules are connected via two hydrogen bonds between the terminal amino group and the oxygen atom of the carbonyl group. The azide units are nearly linear, with dihedral angles of 172.754(2) and 173.542(2)°. All bond lengths are in the expected range. The synthesis of organo-functionalized tin sulfide cluster 3Cl was carried out in two steps (Scheme 3A). A condensation reaction of 3-azido-adamantanecarboxylic acid hydrazide 2 with 4-methyl-4-(trichlorostannyl)-pentane-2-one 10 (R2SnCl3) afforded azido-adamantyl-terminated organotin trichloride 11 (R3SnCl3) in 98% yield, which was characterized by NMR spectroscopy (Supporting Information). Structure 11 was characterized by single crystal X-ray analysis after crystallization from the reaction solution in dichloromethane at −20 °C for 4 months, affording approximately 5% crystalline yield. The organotin trichloride 11 crystallizes in the monoclinic space group P21/c (Z = 4) (Chart 1) with Sn− Cl bond lengths of 2.3601(12)−2.5484(12) Å, which is slightly longer compared to the keto-functionalized organotin trichloride parent compound (2.3286(7)−2.3866(8) Å).24 One chlorine atom engages in two intermolecular hydrogen bonds, one to nitrogen-bonded H2 (2.4404(12) Å) and one to the adamantyl hydrogen atom H9B (2.6980(12) Å). This way, the molecules form an H-bonded chain along the crystallographic c axis. The tin atom is part of one nearly planar five-membered N−N···Sn···O−C ring, together with the nitrogen and oxygen atoms that coordinate to the tin atom in an intramolecular

bifunctional spacer such as 2, consisting of a hydrazide for condensation with keto-terminated cluster 1 and a second orthogonal functionality for the bioconjugation (Scheme 1). The development of such a spacer enables the direct conjunction of tin sulfide clusters with biomolecules without any additional protection or deprotection step. Azides are outstanding substituents that provide excellent chemoselectivity, while possessing intrinsically high reactivity. Structural moieties can be easily connected via Huisgen 1,3-dipolar cycloadditions catalyzed with Cu(I) (CuAAC) or Ru(II) (RuAAC) or strain-promoted with alkynes (SPAAC).18 Moreover, the traceless Staudinger ligation provides the necessary chemoselectivity for modification and derivatization by amide bond formation (Scheme 1).19 Adamantane is an ideal scaffold for this purpose. Its incorporation in peptides or drugs leads to enhanced lipophilicity, rigidity, and stability.20 Moreover, based on our previous findings, diamondoiddecorated tin sulfide clusters exhibit enhanced stability toward moisture and can control the cluster aggregation level depending on the substitution pattern.9,21

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RESULTS AND DISCUSSION 3-Bromo-adamantanecarboxylic acid 5 was synthesized from adamantanecarboxylic acid 4 according to known procedures (Scheme 2A).22 The key step for the synthesis of building block 2 is the incorporation of the azide moiety, afforded by a stannic chloride catalyzed substitution with azidotrimethylsilane.23 Optimization studies indicated the need for the esterification of carboxylic acid 5 prior azide incorporation. Subsequent hydrolysis of ester 7, followed by introduction of the hydrazide moiety via an EDC-mediated coupling with Bochydrazide, and Boc-deprotection afforded bifunctional spacer, B


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Organometallics Scheme 3. Synthesis, Structure, and ESI-MS Spectrum of [(R3Sn)3S4Cl] (3Cl)a

a (A) Synthesis of azido-adamantyl-terminated tin sulfide cluster cation [(R3Sn)3S4Cl] (3Cl), starting from 3-azido-adamantanecarboxylic acid hydrazide 2 and 4-methyl-4-(trichlorostannyl)-pentan-2-one (R2SnCl3). (B) ESI(+)-MS mass spectrum of a solution of the redissolved reaction product containing cluster cations [(R3Sn)3S4]+ (3+). The signal with the highest intensity at m/z = 1434.2389 can be assigned to the desired product 3+, while the signal at m/z = 1215.1073 correlates with sum formula [C40H63N10O3S4Sn3]+, thus illustrating [(R3Sn)2(R2Sn)S4]+ (3a+), in which one original R2 ligand group is recovered.

Chart 1. Packing and Structure of 11a

manner to complete its distorted octahedral environment. The N3−N4−N5 angle is within the range for azides (172.9(7)°). In the second step, azido-adamantyl-terminated organotin trichloride 11 (R3SnCl3) was reacted with 1.3 equiv of (TMS)2S, in order to form the corresponding azido terminated tin sulfide cluster [(R3Sn)3S4Cl] (3Cl) in 45% yield. The cluster [(R3Sn)3S4Cl] (3Cl) was characterized by NMR spectroscopy (1H, 13C, 119Sn), ESI(+)-MS, and X-ray diffraction. The 119Sn NMR spectrum shows only one peak (−103 ppm, see the Supporting Information) shifted downfield with regard to azido-adamantyl-terminated organotin trichloride R3SnCl3, as expected. Consequently, organotin trichloride 11 (R3SnCl3) was completely converted. The ESI(+)-MS mass spectrum shows a mixture of two clusters with different substitution patterns (Scheme 3B). The main signal at m/z = 1434.2389 agrees with a composition of [C51H78N15O3S4Sn3]+, according to desired cluster cation 3+ bearing three R3 substituents. The weaker signal at m/z = 1215.1073 (relative intensity of approximately 5%) can be assigned to a sum formula of [C40H63N10O3S4Sn3]+, according to cluster cation [(R3Sn)2(R2Sn)S4]+ (3a+) binding two adamantyl-terminated ligands R1 and one original ligand R2 (Scheme 3A). We assume that formation of 3a+ takes place under ESI(+)-MS conditions by fragmentation of 3+, as the 119 Sn NMR spectrum shows only one peak. If fragmentation occurred in solution, a second signal with a slightly different

a

Top: Packing of the molecules in the crystal. Ellipsoids are drawn at 50% probability. Nonrelevant hydrogen atoms were omitted for clarity. Bottom: Molecular structure of R3SnCl3 organotin trichloride 11.

C


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Organometallics Chart 2. Molecular Structure of [(R3Sn)3S4Cl] Cluster 3Cl in Two Different Viewsa

a

Ellipsoids are drawn at 50% probability. Nonrelevant hydrogen atoms were omitted for clarity. The disorder of one of the azide groups is indicated by drawing one of the disorder positions in half transparent mode.

Scheme 4. SPAAC and ESI-MS Spectrum of 3Cla

a

(A) SPAAC of azido cluster 3Cl and BCN-containing peptide 12. Note that the substituents are given only once in their full extension, while we abbreviate them elsewhere by using R3 and R4 for clarity. (B) ESI(+) mass spectrum of a solution of the reaction solution from compound 3Cl with 12 with structure proposal for the correlated signals; R3 = CMe2CH2C(NNHC(O)(C10H14N3))Me, R4 = CMe2CH2C(NNHC(O)(C39H53N6O6))Me.

shift is expected to occur in the 119Sn NMR spectrum. This assumption was proven by MS-MS experiments of 3+ (m/z = 1434.2389), in which the second MS experiment led again to the detection of fragmented cluster 3a+ at m/z = 1215.1019 (Figure S24). The structures in Scheme 5B are plausible

suggestions, based on X-ray crystal analysis of trifold azidoadamantyl-terminated cluster 3+ (Chart 2). A solution of the crude compound in dichloromethane was stored at −20 °C for 5 months, leading to crystals of desired product 3Cl in approximately 5% crystalline yield. According to X-ray D


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Organometallics Scheme 5. Low-Field Sections of the

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C NMR Spectra of 12 and 13Cla

a

(A) 13C NMR of BCN-containing peptide 12 in CDCl3. (B) 13C NMR of the crude reaction mixture of SPAAC in CD2Cl2 of 3Cl and 12, displaying cluster 13Cl as product, R4 = CMe2CH2C(NNHC(O)(C39H53N6O6))Me. The reaction mixture includes naphthalene (crossed peaks), deriving from the synthesis of sodium sulfide, which is used in the synthesis of the tin sulfide cluster.25

(2.317(13) Å-2.477(13) Å),9 which is ascribed to the presence of the sterically demanding adamantane substituents. With azido tin sulfide cluster 3Cl in hand, we focused on the postfunctionalization of 3Cl by a strain-promoted azide− alkyne cyclization (SPAAC, Scheme 4A). We have chosen SPAAC for postfunctionalization of azido cluster 3Cl as only a cyclooctyne moiety is needed for the postfunctionalization. Thus, quantitative cyclization would afford postfunctionalized cluster without any side products. BCN (bicyclononyne) was chosen as cyclooctyne derivative, due to its ready accessibility (4 steps)24 and high reactivity in SPAACs.18a Corresponding peptide S4 was synthesized by liquid-phase peptide synthesis and subsequently coupled to the BCN, affording BCNcontaining peptide 12, respectively. SPAAC was performed in an equimolar ratio with respect to the azido group (Scheme 4A). Analysis of the crude reaction mixture after 16 h by NMR showed high dynamic behavior of functionalized cluster 13Cl. Thus, spectroscopy was only possible at 253 K. The 13C NMR displayed quantitative formation of triply functionalized tin sulfide cluster 13Cl, as illustrated in Scheme 5B. The signal corresponding to alkynyl carbons of 12 at 98.9 ppm disappeared (Scheme 5A), and characteristic signals for the triazole carbons (133.5, 146.9 ppm) appeared (Scheme 5B). Furthermore, ESI(+)-MS data were recorded (Scheme 4). The signal at m/z = 3010.1291 agrees with sum formula C138H195N24O21S4Sn3+, thereby illustrating that a 3-fold “click reaction” took place, affording postfunctionalized cluster [(R4Sn)3S4]+ (13+). Additionally the spectrum displays cluster 3+ [(R3Sn)3S4]+ at m/z = 1432.2497, monofunctionalized cluster 13b+ ([(R3Sn)2(R4Sn)S4]+) at m/z = 1959.5434, and difunctionalized cluster 13a+ ([(R3Sn)(R4Sn)2S4]+) at m/z = 2484.8382. On the basis of the analysis via 13C NMR, we assume that the observed signals 3+, 13a+, and 13b+ result from the retrocyclization during the ESI(+)-MS measurement. This proof-of-concept illustrates that the SPAAC is an efficient method for the quantitative postfunctionalization of tin sulfide clusters with biomolecules.

diffraction, the single-crystals comprise a chloride of the cluster cation, [(R3Sn)3S4Cl]·4CH2Cl2 (3Cl). It crystallizes in the triclinic space group P1̅ (Z = 2), with four highly disordered dichloromethane molecules (Table S1). Although all Sn−S bond lengths of 3Cl are within the normal range of similar clusters, the angles within the inorganic core (Sn1−S2−Sn2 103.23(8)°, Sn1−S4−Sn3 103.30(9)°) indicate heavy distortion of the [Sn3S4] defect heterocubane unit. We ascribe this to the steric influence of the adamantyl ligand, which is supported by the fact that corresponding angles are typically 88−93° in comparable [(RSn)3S4Cl] clusters with smaller ligands like hydrazone groups.8d The chlorine atom Cl1 forms three intramolecular hydrogen bonds, one to each of the organic ligands (Cl1···H48B 2.7500(22) Å, Cl1···H1C 2.7775(21) Å, Cl1···H34B 2.8120(33) Å). Two of the hydrogen bonds involve adamantyl substituents, which causes the respective adamantyl groups to be fixed at this position. The interaction with H1C, in contrast, addresses the CH3 group at the Sn-bonded carbon atom of the third organic ligand. Thus, the third adamantane substituent is free to rotate, which is reflected in a rotational disorder, of which two positions were refined (Chart 2). Further mobility of these groups, however, is indicated by a considerable deviation of the N−N−N angle of one of the disorder positions from linearity (N3A−N4A−N5A 148(6)° and N3B−N4B−N5B 175(2)°, whereas the angles of the azides at the rigid adamantyl groups are in the common range (N8−N9−N10 170.8(15)° and N13−N14−N15 171.1(12)°). Atom N5B of the disordered azide is located on the inversion center between two molecules in the unit cell that therefore need to show different rotational positions of their respective azide group. The Sn···N distances in the almost planar five-membered ring range between 2.4328(99) and 2.4471(67) Å, whereas that of Sn1···N1 (2.3765(81) Å) is significantly shorter owing to the hydrogen bond between Cl1 and H1C in trans position. All Sn···N contacts are elongated compared to those in a related cluster E


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Organometallics

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N.; Guo, Z. Metal-based anticancer chemotherapeutic agents. Curr. Opin. Chem. Biol. 2014, 19, 144−153. (e) Lippert, B. Uses of Metal Compounds in Medicine. In Reference Module in Chemistry, Molecular Sciences and Chemical Engineering; Elsevier, 2013. (2) Apps, M. G.; Choi, E. H. Y.; Wheate, N. J. The state-of-play and future of platinum drugs. Endocr.-Relat. Cancer 2015, 22 (4), R219− R233. (3) (a) Larik, F. A.; Saeed, A.; Fattah, T. A.; Muqadar, U.; Channar, P. A. Recent advances in the synthesis, biological activities and various applications of ferrocene derivatives. Appl. Organomet. Chem. 2017, 31, e3664. (b) Delhaes, L.; Biot, C.; Berry, L.; Delcourt, P.; Maciejewski, L. A.; Camus, D.; Brocard, J. S.; Dive, D. Synthesis of Ferroquine Enantiomers: First Investigation of Effects of Metallocenic Chirality upon Antimalarial Activity and Cytotoxicity. ChemBioChem 2002, 3 (5), 418−423. (c) Ornelas, C. Application of ferrocene and its derivatives in cancer research. New J. Chem. 2011, 35 (10), 1973− 1985. (4) Berners-Price, S. J.; Filipovska, A. Gold compounds as therapeutic agents for human diseases. Metallomics 2011, 3 (9), 863−873. (5) (a) Gielen, M. Review: Organotin compounds and their therapeutic potential: a report from the Organometallic Chemistry Department of the Free University of Brussels. Appl. Organomet. Chem. 2002, 16 (9), 481−494. (b) Hong, M.; Geng, H.; Niu, M.; Wang, F.; Li, D.; Liu, J.; Yin, H. Organotin(IV) complexes derived from Schiff base N′-[(1E)-(2-hydroxy-3-methoxyphenyl)methylidene]pyridine-4-carbohydrazone: Synthesis, in vitro cytotoxicities and DNA/BSA interaction. Eur. J. Med. Chem. 2014, 86, 550− 561. (c) Martins, M.; Baptista, P. V.; Mendo, A. S.; Correia, C.; Videira, P.; Rodrigues, A. S.; Muthukumaran, J.; Santos-Silva, T.; Silva, A.; Guedes da Silva, M. F. C.; Gigante, J.; Duarte, A.; Gajewska, M.; Fernandes, A. R. In vitro and in vivo biological characterization of the anti-proliferative potential of a cyclic trinuclear organotin(iv) complex. Mol. BioSyst. 2016, 12 (3), 1015−1023. (6) Omae, I. Organotin antifouling paints and their alternatives. Appl. Organomet. Chem. 2003, 17 (2), 81−105. (7) Nath, M. Toxicity and the cardiovascular activity of organotin compounds: a review. Appl. Organomet. Chem. 2008, 22 (10), 598− 612. (8) (a) Fard, Z. H.; Halvagar, M. R.; Dehnen, S. Directed Formation of an Organotin Sulfide Cavitand and Its Transformation into a Rugby-Ball-like Capsule. J. Am. Chem. Soc. 2010, 132 (9), 2848− 2849. (b) Halvagar, M. R.; Fard, Z. H.; Dehnen, S. Directed derivatization of organotin sulfide compounds: synthesis and selfassembly of an SnS backpack-like cage and a CuSnS ternary cluster. Chem. Commun. 2010, 46 (26), 4716−4718. (c) Barth, B. E. K.; Leusmann, E.; Harms, K.; Dehnen, S. Towards the installation of transition metal ions on donor ligand decorated tin sulfide clusters. Chem. Commun. 2013, 49 (59), 6590−6592. (d) Eußner, J. P.; Barth, B. E. K.; Leusmann, E.; You, Z.; Rinn, N.; Dehnen, S. Functionalized Organotin-Chalcogenide Complexes That Exhibit Defect Heterocubane Scaffolds: Formation, Synthesis, and Characterization. Chem. Eur. J. 2013, 19 (41), 13792−13802. (e) Fard, Z. H.; Xiong, L.; Müller, C.; Hołyńska, M.; Dehnen, S. Synthesis and Reactivity of Functionalized Binary and Ternary Thiometallate Complexes [(RT)4S6], [(RSn)3S4]2−, [(RT)2(CuPPh3)6S6], and [(RSn)6(OMe)6Cu2S6]4− (R = C2H4COOH, CMe2CH2COMe; T = Ge, Sn). Chem. - Eur. J. 2009, 15 (27), 6595−6604. (f) Halvagar, M. R.; Hassanzadeh Fard, Z.; Dehnen, S. Controlling the Architecture of Discrete Organotin Sulfide Molecules by Optimization of the Intramolecular Spacer Length. Chem. - Eur. J. 2011, 17 (16), 4371−4374. (g) You, Z.; Dehnen, S. Directed Formation of a Ferrocenyl-Decorated Organotin Sulfide Complex and Its Controlled Degradation. Inorg. Chem. 2013, 52 (21), 12332−12334. (h) Eußner, J. P.; Dehnen, S. Bronze, silver and gold: functionalized group 11 organotin sulfide clusters. Chem. Commun. 2014, 50 (77), 11385− 11388. (i) Eußner, J. P.; Barth, B. E. K.; Justus, U.; Rosemann, N. W.; Chatterjee, S.; Dehnen, S. Revisiting [(RSnIV)6SnIII2S12]: Directed Synthesis, Crystal Transformation, and Luminescence Properties.

CONCLUSION A novel bifunctional orthogonal spacer was synthesized and applied in the bioconjugation of a tin sulfide cluster via a strain-promoted Huisgen cycloaddition. The spacer, 3-azidoadamantanecarboxylic acid hydrazide 2, was condensed with an keto-functionalized organotin trichloride, which was reacted to a trifold azido-adamantyl-terminated cluster [(R3Sn)3S4Cl] (3Cl, R3 = CMe2CH2C(NNHC(O)(C10H14N3))Me). The cluster was characterized by means of NMR, HRMS, and X-ray crystal structure analysis. Postfunctionalization of this cluster was quantitatively achieved by strain-promoted azide−alkyne cycloaddition “click-reaction”, affording a peptide decorated cluster. Future work will focus on the exploration of the resulting cluster properties.

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.organomet.8b00734. Spectroscopy and spectrometry, synthesis of the ligand, conjugated peptide, tin sulfide cluster, and crystallographic details (PDF) Accession Codes

CCDC 1870760−1870762 contain the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by emailing [email protected], or by contacting The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033.

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AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected]. Web: https://www. uni-marburg.de/fb15/ag-dehnen (S.D.). *E-mail: [email protected]. Web: https://www.uni-giessen. de/fbz/fb08/Inst/organische-chemie/agschreiner (P.R.S.). ORCID

Radim Hrdina: 0000-0001-5060-6666 Stefanie Dehnen: 0000-0002-1325-9228 Peter R. Schreiner: 0000-0002-3608-5515 Author Contributions

J.-P.B. and A.E. are considered equal first authors. Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work was financially supported by LOEWE “SynChemBio”. We thank Eugenie Geringer, Carsten Donsbach, and Eike Dornsiepen for their help with the X-ray diffraction experiments and the crystal structure solutions.

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REFERENCES

(1) (a) Allardyce, C. S.; Dorcier, A.; Scolaro, C.; Dyson, P. J. Development of organometallic (organo-transition metal) pharmaceuticals. Appl. Organomet. Chem. 2005, 19 (1), 1−10. (b) Noffke, A. L.; Habtemariam, A.; Pizarro, A. M.; Sadler, P. J. Designing organometallic compounds for catalysis and therapy. Chem. Commun. 2012, 48 (43), 5219−5246. (c) Hartinger, C. G.; Dyson, P. J. Bioorganometallic chemistry-from teaching paradigms to medicinal applications. Chem. Soc. Rev. 2009, 38 (2), 391−401. (d) Muhammad, F


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Organometallics Inorg. Chem. 2015, 54 (1), 22−24. (j) Hassanzadeh Fard, Z.; Hołyńska, M.; Dehnen, S. Organotin Chalcogenide Salts: Synthesis, Characterization, and Extended Crystal Structures. Inorg. Chem. 2010, 49 (12), 5748−5752. (k) Pohlker, C.; Schellenberg, I.; Pottgen, R.; Dehnen, S. Synthesis and reactivity of ferrocenyl functionalized Sn/S cages. Chem. Commun. 2010, 46 (15), 2605−2607. (l) Hassanzadeh Fard, Z.; Müller, C.; Harmening, T.; Pöttgen, R.; Dehnen, S. Thiostannate Tin−Tin Bond Formation in Solution: In Situ Generation of the Mixed-Valent, Functionalized Complex [{(RSnIV)2(μ-S)2}3SnIII2S6]. Angew. Chem., Int. Ed. 2009, 48 (24), 4441− 4444. (9) Barth, B. E. K.; Tkachenko, B. A.; Eußner, J. P.; Schreiner, P. R.; Dehnen, S. Diamondoid Hydrazones and Hydrazides: Sterically Demanding Ligands for Sn/S Cluster Design. Organometallics 2014, 33 (7), 1678−1688. (10) Halvagar, M. R.; Hassanzadeh Fard, Z.; Xiong, L.; Dehnen, S. Facile Access to the Hydrazone Functionalized PdGeS Cluster [{RNGe(μ-S)3}4Pd6] from the Thiogermanate Anion [{RNGe}2(μS)2S2]2−. Inorg. Chem. 2009, 48 (15), 7373−7377. (11) Rinn, N.; Berndt, J.-P.; Kreher, A.; Hrdina, R.; Reinmuth, M.; Schreiner, P. R.; Dehnen, S. Peptide-Functionalized Organotin Sulfide Clusters. Organometallics 2016, 35 (18), 3215−3220. (12) (a) Rothbard, J. B.; Garlington, S.; Lin, Q.; Kirschberg, T.; Kreider, E.; McGrane, P. L.; Wender, P. A.; Khavari, P. A. Conjugation of arginine oligomers to cyclosporin A facilitates topical delivery and inhibition of inflammation. Nat. Med. 2000, 6 (11), 1253−1257. (b) Dixon, M. J.; Bourré, L.; MacRobert, A. J.; Eggleston, I. M. Novel prodrug approach to photodynamic therapy: Fmoc solidphase synthesis of a cell permeable peptide incorporating 5aminolaevulinic acid. Bioorg. Med. Chem. Lett. 2007, 17 (16), 4518−4522. (c) Lindgren, M.; Rosenthal-Aizman, K.; Saar, K.; Eiríksdóttir, E.; Jiang, Y.; Sassian, M.; Ö stlund, P.; Hällbrink, M.; Langel, Ü . Overcoming methotrexate resistance in breast cancer tumour cells by the use of a new cell-penetrating peptide. Biochem. Pharmacol. 2006, 71 (4), 416−425. (13) Nori, A.; Jensen, K. D.; Tijerina, M.; Kopečková, P.; Kopeček, J. Tat-Conjugated Synthetic Macromolecules Facilitate Cytoplasmic Drug Delivery To Human Ovarian Carcinoma Cells. Bioconjugate Chem. 2003, 14 (1), 44−50. (14) Lewin, M.; Carlesso, N.; Tung, C.-H.; Tang, X.-W.; Cory, D.; Scadden, D. T.; Weissleder, R. Tat peptide-derivatized magnetic nanoparticles allow in vivo tracking and recovery of progenitor cells. Nat. Biotechnol. 2000, 18 (4), 410−414. (15) Stewart, K. M.; Horton, K. L.; Kelley, S. O. Cell-penetrating peptides as delivery vehicles for biology and medicine. Org. Biomol. Chem. 2008, 6 (13), 2242−2255. (16) (a) Sletten, E. M.; Bertozzi, C. R. Bioorthogonal Chemistry: Fishing for Selectivity in a Sea of Functionality. Angew. Chem., Int. Ed. 2009, 48 (38), 6974−6998. (b) Debets, M. F.; van Hest, J. C. M.; Rutjes, F. P. J. T. Bioorthogonal labelling of biomolecules: new functional handles and ligation methods. Org. Biomol. Chem. 2013, 11 (38), 6439−6455. (c) Patterson, D. M.; Nazarova, L. A.; Prescher, J. A. Finding the Right (Bioorthogonal) Chemistry. ACS Chem. Biol. 2014, 9 (3), 592−605. (17) (a) Proust, A.; Matt, B.; Villanneau, R.; Guillemot, G.; Gouzerh, P.; Izzet, G. Functionalization and post-functionalization: a step towards polyoxometalate-based materials. Chem. Soc. Rev. 2012, 41 (22), 7605−7622. (b) Micoine, K.; Hasenknopf, B.; Thorimbert, S.; Lacôte, E.; Malacria, M. A General Strategy for Ligation of Organic and Biological Molecules to Dawson and Keggin Polyoxotungstates. Org. Lett. 2007, 9 (20), 3981−3984. (18) (a) Debets, M. F.; van Berkel, S. S.; Dommerholt, J.; Dirks, A. J.; Rutjes, F. P. J. T.; van Delft, F. L. Bioconjugation with Strained Alkenes and Alkynes. Acc. Chem. Res. 2011, 44 (9), 805−815. (b) Johansson, J. R.; Beke-Somfai, T.; Said Stålsmeden, A.; Kann, N. Ruthenium-Catalyzed Azide Alkyne Cycloaddition Reaction: Scope, Mechanism, and Applications. Chem. Rev. 2016, 116 (23), 14726− 14768. (c) Hein, J. E.; Fokin, V. V. Copper-catalyzed azide-alkyne

cycloaddition (CuAAC) and beyond: new reactivity of copper(i) acetylides. Chem. Soc. Rev. 2010, 39 (4), 1302−1315. (19) (a) Nilsson, B. L.; Kiessling, L. L.; Raines, R. T. Staudinger Ligation: A Peptide from a Thioester and Azide. Org. Lett. 2000, 2 (13), 1939−1941. (b) Saxon, E.; Armstrong, J. I.; Bertozzi, C. R. A “Traceless” Staudinger Ligation for the Chemoselective Synthesis of Amide Bonds. Org. Lett. 2000, 2 (14), 2141−2143. (c) Schilling, C. I.; Jung, N.; Biskup, M.; Schepers, U.; Bräse, S. Bioconjugation viaazideStaudinger ligation: an overview. Chem. Soc. Rev. 2011, 40 (9), 4840− 4871. (20) Wanka, L.; Iqbal, K.; Schreiner, P. R. The Lipophilic Bullet Hits the Targets: Medicinal Chemistry of Adamantane Derivatives. Chem. Rev. 2013, 113 (5), 3516−3604. (21) (a) Müller, C. E.; Wanka, L.; Jewell, K.; Schreiner, P. R. Enantioselective Kinetic Resolution of trans-Cycloalkane-1,2-diols. Angew. Chem., Int. Ed. 2008, 47 (33), 6180−6183. (b) Wende, R. C.; Seitz, A.; Niedek, D.; Schuler, S. M. M.; Hofmann, C.; Becker, J.; Schreiner, P. R. The Enantioselective Dakin−West Reaction. Angew. Chem., Int. Ed. 2016, 55 (8), 2719−2723. (22) (a) Wanka, L.; Cabrele, C.; Vanejews, M.; Schreiner, P. R. γAminoadamantanecarboxylic Acids Through Direct C−H Bond Amidations. Eur. J. Org. Chem. 2007, 2007, 1474−1490. (b) Harman, D. G.; Blanksby, S. J. Investigation of the gas phase reactivity of the 1adamantyl radical using a distonic radical anion approach. Org. Biomol. Chem. 2007, 5 (21), 3495−3503. (23) (a) Prakash, G. K. S.; Stephenson, M. A.; Shih, J. G.; Olah, G. A. Synthetic methods and reactions. 125. Preparation of secondary and tertiary cyclic and polycyclic hydrocarbon azides. J. Org. Chem. 1986, 51 (16), 3215−3217. (b) Yoshida, S.; Nonaka, T.; Morita, T.; Hosoya, T. Modular synthesis of bis- and tris-1,2,3-triazoles by permutable sequential azide-aryne and azide-alkyne cycloadditions. Org. Biomol. Chem. 2014, 12 (38), 7489−7493. (24) Dommerholt, J.; Schmidt, S.; Temming, R.; Hendriks, L. J. A.; Rutjes, F. P. J. T.; van Hest, J. C. M.; Lefeber, D. J.; Friedl, P.; van Delft, F. L. Readily Accessible Bicyclononynes for Bioorthogonal Labeling and Three-Dimensional Imaging of Living Cells. Angew. Chem., Int. Ed. 2010, 49 (49), 9422−9425. (25) So, J.-H.; Boudjouk, P.; Hong, H. H.; Weber, W. P. Hexamethyldisilathiane. Inorg. Synth. 2007, 29, 30.

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Azido-Adamantyl Tin Sulfide Clusters for Bioconjugation

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