Synthesis and characterization of complexes of the {ReO}³⁺ core with SNS and S donor ligands

Abstract

The reaction of [ReOCl₃(PPh₃)₂] with N,N-bis(2-mercaptoethyl)benzylamine and 4-bromobenzenethiol allowed for the isolation of [ReO{η³-(SCH₂CH₂)₂N(CH₂C₆H₅)}-(η¹-C₆H₄Br-4-S)] (1). The reaction of [ReOCl₃(PPh₃)₂] with [(HSCH₂CH₂)₂N(CH₂C₅H₄N)] and the appropriate thiol in chloroform treated with triethylamine has led to the isolation of a series of neutral rhenium complexes of the type [ReO{η³-(SCH₂CH₂)₂N(CH₂C₅H₄N)}(η¹-C₆H₄X-4-S)] (X = Br (2), Cl (3), F (4), and OCH₃ (5)) and [ReO{η³-(SCH₂CH₂)₂N(CH₂C₅H₄N)}(η¹-C₆H₄OCH₃-4-CH₂S)] (6). Likewise, under similar reaction conditions, the use of the related tridentate ligand, [(HSCH₂CH₂)₂N(CH₂CH₂C₅H₄N)], has led to the isolation of a series of rhenium complexes of the type [ReO{η³-(SCH₂CH₂)₂N(CH₂CH₂C₅H₄N)}(η¹-C₆H₄X-4-S)] (X=Br (7), Cl (8), OCH₃ (9)), as well as [ReO{η³-(SCH₂CH₂)₂N(CH₂CH₂C₅H₄N)}(η¹-C₆H₄Cl-4-CH₂S)]·0.5CH₃(CH₂)₄CH₃ (10). These compounds are extensions of the ‘3+1’ approach to the synthesis of materials with the {MO}³⁺ core (M=Tc and Re), which have applications in nuclear medicine. The ligands chosen allow systematic exploration of the consequences of para-substitution on the monodentate thiolate ligand [S] and of derivatization of the substituent R on the tridentate aminodithiol ligand [SNS] of the type (HSCH₂CH₂)₂NR. Such modifications can influence lipophilicity, charge, size and molecular weight of the complex and consequently the biodistribution.

1. Introduction

The significant contemporary interest in the coordination chemistry of rhenium derives from its analogies to technetium chemistry, as well as its expanding role in therapeutic nuclear chemistry [1]. The radionuclides of Re, the Group 7 congener of technetium, are β-emitters with properties which make them suitable candidates for therapeutic applications. Rhenium-186 is particularly attractive [2–4] because of its half-life (90 h) and strong β-emission (β_max, 1070 keV), capable of delivering high radiation doses to tissues. Rhenium-188, also a β-emitting radionuclide (β_max, 2120 keV), with a half-life of 17 h and available from a ¹⁸⁸W/¹⁸⁸Re radionuclide generator at no carrier added levels [5], has become a logical choice for the development of radio-pharmaceuticals for use in the treatment of cancer [1].

The synthesis of novel compounds, which allow the systematic exploration of size, shape, molecular weight, and charge of the metal–thiolate complexes with respect to their biodistribution patterns, provides a driving force for advances in the radiopharmaceutical chemistry of rhenium. One approach to the systematic design of Re(V) complexes with the {ReO}³⁺ core exploits the ‘3+1’ concept of ligand addition to a Group 7 metal-oxo species [6–16]. The methodology is based on forming a tridentate ‘3’ and a monodentate ‘1’ mixed-thiolate core. The technique uses tridentate dithiolates with the (S–X–S)²⁻ (X=NR, O, S) donor set and a −2 charge in combination with a monothiol ligand of −1 charge disposed about a Group 7 metal-oxo core, so as to occupy four coordination sites on the metal with a total formal charge of −3. The ‘3+1’ ligand combination preserves the metal-oxo core and the formal +5 oxidation state of the metal, thus conforming to the metal coordination and oxidation preferences.

Over the past decade, thiol based tridentate ligands have received significant attention in the design of new Group 7 metal-oxo complexes [8–11,17–31]. One such series of compounds belongs to the class of [SSS]/[S] ‘3+1’ mixed ligand complexes [10,11,17–21]. Numerous groups have synthesized neutral rhenium and technetium compounds containing 2-mercaptoethyl sulfide as the tridentate in combination with various monothiols, to produce complexes such as [ReO{(SCH₂CH₂)₂-S}{SCH₂C₆H₅}] [11], [ReO{(SCH₂CH₂)₂S}{SCH₂CH-(OH)CH(OH)CH₂SH}] [17], [ReO{(SCH₂CH₂)₂S}-{S(CH₂)₃N(CH₃)(CH₂)₃C₆H₅}] [18] and [ReO{(SCH₂C-H₂)₂S}{SCH₂CH(CH₂CH₃)-4-HOC₆H₅}] [19]. Not only have such neutral compounds reported but also several cationic complexes such as [ReO{(SCH₂CH₂)₂S}-{C₅H₄NH-2-S}][Br] [20].

Another subclass of compounds includes the class of [SOS]/[S] ‘3+1’ mixed ligand complexes [11,21,22]. In most instances of this family of compounds, the tridentate 2-mercaptoethylether seems to be the tridentate of choice, and has been used in the design of such neutral compounds as [ReO{(SCH₂CH₂)₂O}{SC₆H₅}] [11] and [ReO{(SCH₂CH₂)₂O}{SCH₂-4-CH₃OC₆H₅}] [22], a cationic species [ReO{(SCH₂CH₂)₂O}{C₅H₄NH-2-S}] [22], and several binuclear complexes, of which [Tc₂O₂{(SC-H₂CH₂)₂O}₂{SCH₂CH₂OCH₂CH₂S}] [21] and [Re₂-O₂{(SCH₂CH₂)₂O}₂{SCH₂CH₂OCH₂CH₂S}] [22] are representatives.

A third series of ‘3+1’ complexes includes the [ONS]/[S] mixed ligand complexes [8,9,20,23–27]. One subclass of this family incorporates the tridentate Schiff base [HOC₆H₄C(H)NC₆H₄SH] and includes complexes such as [TcO{OC₆H₄C(H)NC₆H₄S}{SC₆H₅}] [9], [TcO-{OC₆H₄C(H)NC₆H₄S}{n-SC₈H₁₇}] [8], and a cationic species [ReO{OC₆H₄C(H)NC₆H₄S}{C₅H₄NH-2-S}][Br] [23]. Another tridentate ligand type found in the [ONS]/[S] series is represented by [C₅H₃N-2-CH₂OH-6-CH₂SH], which allows isolation of both neutral compounds, such as [ReO{C₅H₃N-2-CH₂O-6-CH₂S}{S-4-ClC₆H₄}] [27], and cationic species, [ReO{C₅H₃N-2-CH₂O-6-CH₂S}{C₅H₄NH-2-S}][Br] [20].

The vast majority of the ‘3+1’ Group 7 metal-oxo complexes belong to the class [SN(R)S]/[S], where the −R group of the tridentate may be exploited to provide a variety of derivatives and secondary functionality [19,28–31]. Examples include [ReO{C₅H₃N(CH₂S)₂}{S-4-C₆H₄OH}] [19], [ReO{C₂H₅N(CH₂CH₂S)₂}{S-4-Cl-C₆H₄}] [28], [ReO{C₂H₅SCH₂CH₂N(CH₂CH₂S)₂}{S-4-CH₃OC₆H₄}] [29], a binuclear complex [Re₂-O₂{C₂H₅N(CH₂CH₂S)₂}₃] [28] and a cationic species, [ReO{C₅H₃N(CH₂S)₂}{C₅H₄NH-2-S}][Cl] [27].

In an effort to expand the ‘3+1’ chemistry to the oxo-rhenium core, our work has concentrated on the reactions of the tridentate thiol, [(HSCH₂CH₂)₂N-(CH₂C₆H₅)], and the potentially tetradentate ligands-[(HSCH₂CH₂)₂N(CH₂C₅H₄N)] and [(HSCH₂CH₂)₂-N(CH₂CH₂C₅H₄N)] with [ReOCl₃(PPh₃)₂], so as to prepare families of compounds with mixed thiol ligands, and allowing the systematic exploration of the para-substituted benzenethiol and benzylmercaptan series. This study continues our development of the coordination chemistry of the Group 7 metal rhenium [17,20,22,23,27], in order to provide new materials for radiolabeling of chemotatic peptides [32]. We report the synthesis and structural characterization of a series of oxo-rhenium ‘3+1’ complexes, namely [ReO{η³-(SC-H₂CH₂)₂N(CH₂C₆H₅)}(η¹-C₆H₄Br-4-S)] (1), [ReO{η³-(SCH₂CH₂)₂N(CH₂C₅H₄N)}(η¹-C₆H₄X-4-S)] (X=Br (2), Cl (3), F (4), and OCH₃ (5)), [ReO{η³-(SC-H₂CH₂)₂N(CH₂C₅H₄N)}(η¹-C₆H₄OCH₃-4-CH₂S)] (6), [ReO{η³ - (SCH₂CH₂)₂N(CH₂CH₂C₅H₄N)}(η¹ - C₆H₄-X-4-S)] (X=Br (7), Cl (8), OCH₃ (9)), and [ReO{η³-(SCH₂CH₂)₂N(CH₂CH₂C₅H₄N)}(η¹-C₆H₄Cl-4-CH₂S)]· 0.5CH₃(CH₂)₄CH₃ (10).

2. Experimental

2.1. General considerations

NMR spectra were recorded on a Bruker DPX 300 (¹H 300.10 MHz) spectrometer in CDCl₃ (δ 7.27). IR spectra were recorded as KBr discs with a Perkin–Elmer series 1600 FT IR. Elemental analysis for carbon, hydrogen, and nitrogen were carried out by Oneida Research Services, Whitesboro, NY. Ammonium perrhenate (Aldrich), triethylamine (Aldrich), triphenylphosine (Aldrich), benzylamine (Aldrich), 2-(aminomethyl)pyridine (Aldrich), ethylene sulfide (Aldrich), 2-(2-aminoethyl)pyridine (Aldrich), 4-bromobenzenethiol (Aldrich), 4-chlorobenzenethiol (Aldrich), 4-fluorobenzenethiol (Aldrich), 4-methoxy-benzenethiol (Aldrich), 4-chlorobenzyl mercaptan (Aldrich), 4-methoxybenzyl mercaptan (Lancaster) were used as received without further purification. All other solvents and reagents were purchased from Aldrich and used as received, unless otherwise stated. The [ReOCl₃(PPh₃)₂] [33] and N,N-bis(2-mercapto-ethyl)benzylamine [34] were synthesized according to published procedures.

2.2. Syntheses

2.2.1. [(HSCH₂CH₂)₂N(CH₂C₅H₄N)]

A similar procedure was employed as for the preparation of N,N-bis(2-mercaptoethyl)benzylamine. ¹H NMR (CDCl₃, ppm): 1.72 (s, 2H), 2.61 (m, 4H), 2.78 (m, 4H), 3.81 (s, 2H), 7.18 (m, 1H), 7.36, (d, 1H), 7.67 (m, 1H), 8.52 (m, 1H).

2.2.2. [(HSCH₂CH₂)₂N(CH₂CH₂C₅H₄N)]

A similar procedure was employed as for the preparation of N,N-bis(2-mercaptoethyl)benzylamine. ¹H NMR (CDCl₃, ppm): 1.75 (s, 2H), 2.10–2.90 (m, 12H), 7.18 (m, 1H), 7.20, (d, 1H), 7.60 (t, 1H), 8.50 (d, 1H).

2.2.3. General synthetic procedure

To a solution of [ReOCl₃(PPh₃)₂] (0.0822 g, 0.0986 mmol) in 1 ml of chloroform was added dropwise a solution of 1 equiv. (0.0986 mmol) of monothiol (the HSR donor ligand) and 1 equiv. of the dithiol [(HSCH₂CH₂)₂NR, R=CH₂C₆H₅, CH₂C₅H₄N, (CH₂)₂C₅H₄N] (0.0986 mmol) in 1 ml of chloroform. The solution remained olive green until the addition of triethylamine (0.08 ml, 0.574 mmol) whereupon it immediately changed from olive to forest green. The solution was stirred and refluxed for an additional 30 min and then evaporated to dryness. Crystals for each of the compounds were grown as indicated.

2.2.3.1. Preparation of [ReO{η³-(SCH₂CH₂)₂N(CH₂ -C₆H₅)}(η¹-C₆H₄Br -4 -S)] (1)

X-ray quality crystals were grown by slow diffusion of pentane in a solution of the compound in methylene chloride (yield: 0.021 g, 34.6%). Anal. Calc. for C₁₇H₁₉NOS₃BrRe (mol. wt. 615.62): C, 33.2; H, 3.11; N, 2.28. Found: C, 32.5; H, 3.49; N, 2.16%.

2.2.3.2. Preparation of [ReO{η³-(SCH₂CH₂)₂N(CH₂ -C₅H₄N)}(η¹-C₆H₄Br -4 -S)] (2)

X-ray quality crystals were grown by slow diffusion of pentane in a solution of the compound in methylene chloride (yield: 0.027 g, 44.4%). IR (KBr, cm⁻¹): 1654 (m), 1560 (m), 1508 (w), 1267 (m), 1080 (m), 1008 (m), 948 (s), 813 (w). ¹H NMR (CDCl₃, ppm): 2.73 (m, 2H), 2.85 (m, 2H), 3.52 (m, 2H), 3.85 (m, 2H), 5.03 (s, 2H), 7.26 (m, 2H), 7.38 (m, 2H), 7.53 (m, 2H), 7.80 (m, 1H), 8.71 (m, 1H).

2.2.3.3. Preparation of [ReO{η³-(SCH₂CH₂)₂N(CH₂ -C₅H₄N)}(η¹-C₆H₄Cl -4 -S)] (3)

X-ray quality crystals were grown by slow diffusion of diethylether into a methylene chloride solution of 3 (yield: 0.019 g, 33.9%). IR (KBr, cm⁻¹): 1654 (m), 1560 (m), 1508 (w), 1266 (m), 1085 (m), 1012 (m), 949 (s), 818 (w). ¹H NMR (CDCl₃, ppm): 2.72 (m, 2H), 2.83 (m, 2H), 3.52 (m, 2H), 3.86 (m, 2H), 5.03 (s, 2H), 7.35 (m, 2H), 7.41 (m, 2H), 7.73 (m, 2H), 7.82 (m, 1H), 8.71 (m, 1H). Anal. Calc. for C₁₆H₁₈N₂OS₃ClRe (mol. wt. 572.15): C, 33.6; H, 3.17; N, 4.90. Found: C, 34.1; H, 3.55; N, 4.07%.

2.2.3.4. Preparation of [ReO{η³-(SCH₂CH₂)₂N(CH₂ -C₅H₄N)}(η ¹-C₆H₄F -4 -S)] (4)

X-ray quality crystals were grown by slow diffusion of pentane into a methylene chloride solution of 4 (yield: 0.025 g, 45.6%). IR (KBr, cm⁻¹): 1654 (m), 1560 (w), 1508 (w), 1263 (s), 1154 (m), 1014 (m), 942 (s), 833 (w). ¹H NMR (CDCl₃, ppm): 2.69 (m, 2H), 2.83 (m, 2H), 3.53 (m, 2H), 3.85 (m, 2H), 5.03 (s, 2H), 7.09 (m, 2H), 7.39 (m, 2H), 7.63 (m, 2H), 7.80 (m, 1H), 8.71 (m, 1H).

2.2.3.5. Preparation of [ReO{η³-(SCH₂CH₂)₂N(CH₂ -C₅H₄N)}(η¹-C₆H₄OCH₃ -4 -S)] (5)

X-ray quality crystals were grown by slow diffusion of pentane into a solution of the compound in methylene chloride (yield: 0.023 g, 41.1%). IR (KBr, cm⁻¹): 1654 (m), 1560 (w), 1508 (w), 1283 (s), 1172 (m), 1028 (m), 941 (s), 828 (w). ¹H NMR (CDCl₃, ppm): 2.71 (m, 2H), 2.84 (m, 2H), 3.55 (m, 2H), 3.82 (m, 2H), 3.88 (s, 3H), 5.07 (s, 2H), 6.95 (m, 2H), 7.37 (m, 2H), 7.61 (m, 2H), 7.79 (m, 1H), 8.72 (m, 1H).

2.2.3.6. Preparation of [ReO{η3-(SCH2CH2)2N(CH2 -C5H4N)}(η ¹-C₆H₄OCH₃ -4 -CH₂S)] (6)

X-ray quality crystals were grown by slow diffusion of diethylether into a methylene chloride solution of 6 (yield: 0.027 g, 47.1%). IR (KBr, cm⁻¹): 1654 (m), 1560 (w), 1509 (w), 1248 (s), 1104 (m), 1032 (m), 948 (s), 819 (w). ¹H NMR (CDCl₃, ppm): 2.61 (m, 2H), 3.01 (m, 2H), 3.53 (m, 2H), 3.81 (s, 3H), 3.87 (m, 2H), 4.89 (s, 2H), 5.00 (s, 2H), 6.84 (m, 2H), 7.34 (m, 2H), 7.41 (m, 2H), 7.76 (m, 1H), 8.71 (m, 1H). Anal. Calc. for C₁₈H₂₃N₂O₂S₃Re (mol. wt. 581.76): C, 37.2; H, 3.98; N, 4.82. Found: C, 36.8; H, 3.73; N, 4.55%.

2.2.3.7. Preparation of [ReO{η³-(SCH₂CH₂)₂N(CH₂ -CH₂C₅H₄N)}(η ¹-C₆H₄Br -4 -S)] (7)

X-ray quality crystals were grown by slow diffusion of pentane into a methylene chloride solution of 7 (yield: 0.031 g, 49.9%). IR (KBr, cm⁻¹): 1654 (m), 1578 (w), 1438 (w), 1273 (s), 1095 (m), 1029 (m), 943 (s), 846 (w). ¹H NMR (CDCl₃, ppm): 2.76 (m, 2H), 2.91 (m, 2H), 3.31 (t, 2H), 3.42 (m, 2H), 3.68 (m, 2H), 4.19 (m, 2H), 7.24 (m, 2H), 7.32 (m, 2H), 7.51 (m, 2H), 7.67 (m, 1H), 8.56 (m, 1H). Anal. Calc. for C₁₇H₂₀N₂OS₃BrRe (mol. wt. 630.64): C, 32.4; H, 3.20; N, 4.44. Found: C, 32.9; H, 3.36; N, 4.38%.

2.2.3.8. Preparation of [ReO{η3-(SCH₂CH₂)₂N(CH₂ -CH₂C₅H₄N)}(η¹-C₆H₄Cl -4 -S)] (8)

Crystals were grown by slow diffusion of pentane into a solution of the compound in methylene chloride (yield: 0.024 g, 41.5%). IR (KBr, cm⁻¹): 1654 (m), 1574 (w), 1472 (w), 1268 (s), 1090 (m), 1009 (m), 947 (s), 816 (w). ¹H NMR (CDCl₃, ppm): 2.79 (m, 2H), 2.89 (m, 2H), 3.31 (t, 2H), 3.42 (m, 2H), 3.68 (m, 2H), 4.20 (m, 2H), 7.22 (m, 2H), 7.33 (m, 2H), 7.55 (m, 2H), 7.68 (m, 1H), 8.57 (m, 1H). Anal. Calc. for C₁₇H₂₀N₂OS₃ClRe (mol. wt. 586.19): C, 34.8; H, 3.44; N, 4.78. Found: C, 33.6; H, 3.21; N, 2.84%.

2.2.3.9. Preparation of [ReO{η³-(SCH₂CH₂)₂N(CH₂ -CH₂C₅H₄N)}(η¹-C₆H₄OCH₃ -4 -S)] (9)

X-ray quality crystals were grown by slow diffusion of diethylether into a solution of the compound in methylene chloride (yield: 0.023 g, 40.1%). IR (KBr, cm⁻¹): 1654 (m), 1577 (m), 1492 (w), 1283 (s), 1171 (m), 1024 (m), 938 (s), 826 (w). ¹H NMR (CDCl₃, ppm): 2.76 (m, 2H), 2.90 (m, 2H), 3.30 (t, 2H), 3.40 (m, 2H), 3.65 (m, 2H), 3.83 (s, 3H), 4.18 (m, 2H), 6.93 (m, 2H), 7.22 (m, 2H), 7.54 (m, 2H), 7.67 (m, 1H), 8.56 (m, 1H).

2.2.3.10. Preparation of [ReO{η³-(SCH₂CH₂)₂N(CH₂ -CH₂C₅H₄N)}(η¹-C₆H₄Cl -4 -CH₂S)] · 0.5CH₃(CH₂)₄CH₃ (10)

X-ray quality crystals were grown by slow diffusion of hexane into a methylene chloride solution of 10 (yield: 0.028 g, 44.2%). IR (KBr, cm⁻¹): 1650 (m), 1589 (w), 1487 (w), 1263 (s), 1090 (m), 1009 (m), 948 (s), 831 (w). ¹H NMR (CDCl₃, ppm): 2.71 (m, 2H), 3.01 (m, 2H), 3.30 (t, 2H), 3.43 (m, 2H), 3.69 (m, 2H), 4.15 (m, 2H), 4.83 (s, 2H), 7.19–7.27 (m, 4H), 7.33 (m, 2H), 7.65 (m, 2H), 8.56 (m, 1H).

2.3. X-ray crystallography

All data were collected on a Bruker SMART diffractometer system using graphite monochromated Mo Kα radiation (λ(Mo Kα)=.71073 Å). All the data collections were carried out at low temperature (87–93 K). The crystal parameters and other experimental details of the data collections are summarized in Table 1. A complete description of the details of the crystallographic methods is given in Supporting Information. Data was corrected for Lorentz and polarization effects, and absorption corrections were made using SAD-ABS [35]. The structures were solved by direct methods [36]. Neutral atom scattering factors were taken from Cromer and Waber [37] and anomalous dispersion corrections were taken from those of Creagh and McAuley [38]. All calculations were preformed using SHELXTL-96 [36]. Non-hydrogen atoms were refined anisotropically. No anomalies were encountered in the refinements of any of the structures. Atomic positional parameters for the structures have been deposited with the Cambridge Structural Database (Section 5).

Table 1.

Summary of the crystallographic data for the compounds (1–10)

	1	2	3	4	5	6	7	9	10
Chemical formula	C17H19NOS3BrRe	C16H18N2OS3BrRe	C16H18N2OS3ClRe	C16H18N2OS3FRe	C17H21N2O2S3Re	C18H23N2O2S3Re	C17H20N2OS3BrRe	C18H23N2O2S3Re	C21H29N2OS3ClRe
a (Å)	11.2989(6)	9.3051(7)	9.3247(4)	8.9720(5)	9.4042(4)	8.3855(4)	9.4161(4)	11.6331(4)	11.2621(7)
b (Å)	13.1804(7)	9.5482(7)	9.4485(4)	9.4770(5)	9.4183(4)	24.8281(12)	9.5641(4)	10.4400(4)	12.0955(7)
c (Å)	13.5621(8)	11.4612(8)	11.3743(5)	11.6194(6)	11.5443(5)	9.7181(5)	12.0349(5)	16.5754(6)	16.5589(10)
α (°)	80.791(1)	69.709(1)	70.320 (1)	72.876(1)	111.975(1)	90	109.8550(10)	90	85.1660(10)
β (°)	75.088(1)	74.940(1)	74.615(1)	70.865(1)	100.927(1)	104.9880(10)	104.4130(10)	105.5100(10)	74.3980(10)
γ (°)	78.042(1)	86.287(1)	84.808(1)	81.471(1)	90.201(1)	90	91.9330(10)	90	85.7420(10)
V (Å3)	1897.15(18)	921.94(12)	909.78(7)	890.54(8)	927.90(7)	1954.44(17)	978.80(7)	1939.77(12)	2161.7(2)
Z	4	2	2	2	2	4	2	4	4
Formula weight	615.62	616.61	572.15	555.70	567.74	581.76	630.64	581.76	643.29
Space group	P1̄	P1̄	P1̄	P1̄	P1̄	P 21/n	P1̄	P21/n	P1̄
T (K)	89(5)	87(5)	87(5)	88(5)	90(5)	87(5)	89(5)	90(5)	93(5)
λ (Å)	0.71073	0.71073	0.71073	0.71073	0.71073	0.71073	0.71073	0.71073	0.71073
Dcalc (g cm−1)	2.155	2.221	2.089	2.072	2.032	1.977	2.140	1.992	1.977
μ (mm−1)	8.846	9.103	7.176	7.190	6.899	6.554	8.577	6.603	6.052
Ra	0.0439	0.0665	0.0289	0.0426	0.0315	0.0641	0.0345	0.0342	0.0560
wR2b	0.0832	0.1158	0.0710	0.1127	0.0710	0.0744	0.0753	0.0534	0.1238

^aΣ|F_o| − |F_c|/Σ|F_o|.

^b ${[\mathrm{\sum }[w{(F_{\text{o}}^2-F_{\text{c}}^2)}^2]/\mathrm{\sum }[w{(F_{\text{o}}^2)}^2]]}^{1/2}$.

3. Results and discussion

The synthesis of N,N-bis(2-mercaptoethyl)benzylamine employs the route of Schröder and coworkers [34], in which 4 equiv. of ethylene sulfide are reacted with 1 equiv. of benylamine at 65°C for 48 h. A similar procedure was employed in the synthesis of [(HSCH₂-CH₂)₂N(CH₂C₅H₄N)] and [(HSCH₂CH₂)₂N(CH₂CH₂-C₅H₄N)] starting from the appropriate amines, 2-(aminomethyl)pyridine and 2-(2-aminoethyl)pyridine, respectively.

The compounds of this study were all prepared readily from the reactions of the appropriate ligands with [ReOCl₃(PPh₃)₂]. While [Bu₄N][ReOBr₄(OPPh₃)] also proved to be an effective starting material, there was no advantage to its use in terms of yield or product purity. Since the synthesis of [Bu₄N][ReOBr₄(OPPh₃)] is relatively involved and of low yield, the more easily prepared and purified starting material [ReOCl₃(PPh₃)₂] was used exclusively for the synthesis of 1–10. The green solid is indefinitely air and moisture stable making it suitable for probing the reactivities of a variety of ligand types. Consequently, the compounds of this study were synthesized in a straightforward fashion from the reaction of [ReOCl₃(PPh₃)₂] with one equivalent of the tridentate dithiol ligand (or ‘3’ ligand) and 1 equiv. of the monodentate thiol ligand (or ‘1’ ligand) in chloroform. An addition of excess triethylamine produces a forest green solution, which upon workup yields crystalline products 1–10.

The infrared spectrum of 2–10 are characterized by a series of ligand bands in the 1008–1654 cm⁻¹ range and a strong band in the 938–949 cm⁻¹ range attributed to ν(Re=O). The ¹H NMR spectra of compounds 2–6 are unexceptional. All display a series of multiplets ranging from 6.84 to 8.72 ppm assignable to the eight aromatic protons, as well as four multiplets at 2.69, 2.87, 3.53, and 3.85 ppm assignable to each CH₂ moiety comprising the backbone of the tridentate ligand (⁻SCH₂CH₂N(R)CH₂CH₂S⁻). All four of the multiplets integrate to two protons; however, individual assignments of the resonances are tenuous at best, due to the multiplicity of the peaks and the flexibility of the ligand in solution, as noted by others [6]. In addition, compounds 2–6 also displayed a single proton resonance integrating to two protons at 5.03 ppm corresponding to the methylene spacer of the tridentate backbone. Furthermore, [ReO{η³-(SCH₂CH₂)₂N(CH₂-C₅H₄N)}(η¹-C₆H₄OCH₃-4-S)] (5) and [ReO{η³-(SCH₂-CH₂)₂N(CH₂C₅H₄N)}(η¹-C₆H₄OCH₃-4-CH₂S)] (6) exhibited an additional singlet at approximately 3.88 and 3.81 ppm, respectively, which is attributed to the three protons of the methoxy group. The monodentate benzylmercaptan of compound 6 displayed methylene protons at approximately 4.89 ppm as a single peak, as anticipated from Sadtler spectra [39].

Similarly, the ¹H NMR spectra for compounds 7–10 contain multiplets at 2.76, 2.93, 3.42, and 3.68 ppm assignable to each CH₂ moiety comprising the backbone of the tridentate ligand, as well as series of multiplets ranging from 6.93 to 8.57 ppm assignable to the eight aromatic protons. Compounds 7–10 also displayed a triplet at 3.31 ppm and a multiplet at 4.18 ppm each integrating to two protons and corresponding to the ethylene spacer of the tridentate ligand. In addition, the monodentate benzylmercaptan of compound 10 displayed methylene protons at approximately 4.83 ppm as a single peak, as anticipated from Sadtler spectra [38]. [ReO{η³-(SCH₂CH₂)₂N(CH₂CH₂C₅-H₄N)}(η¹-C₆H₄OCH₃-4-S)] (9) exhibited an additional singlet at approximately 3.83 ppm, which is attributed to the three protons of the methoxy group. In no case does the ¹H NMR data suggest the presence of syn/anti isomers with respect to the amine substituent R and the oxo-group orientations. The crystal structure data, likewise, confirm that all compounds adopt the syn geometry exclusively.

As shown in Fig. 1, the coordination geometry around the metal for [ReO{η³-(SCH₂CH₂)₂-N(CH₂C₆H₅)}(η¹-C₆H₄Br-4-S)] (1) is distorted trigonal bipyramidal, with the oxo group and the sulfur atoms of the [SNS] ligand defining the equatorial plane and the axial positions occupied by the sulfur atom of the monothiol and the nitrogen atom of the [SNS] ligand. The angles between the atoms in the equatorial plane are close to the ideal 120° (Table 2), but a value of 157.91(15)° observed for the N(1)–Re(1)–S(3) angle indicates a distortion of the trigonal bipyramid, which can also be seen in the value of the trigonality index [40], τ=0.61. The bond distances in the coordination environment of the metal are characteristic for this type of complexation [31]. The Re=O bond length is found to be 1.699(5) Å well within the range observed for other {ReO}³⁺ complexes [24,31,41–52]. Likewise, the Re–N bond length [Re–N(1)= 2.208(6) Å] is typical for the Re–N_amine single bond in which the nitrogen atom exhibits sp³ hybridization [24,31,41–52]. However, in the case of the metal–sulfur bond lengths, those in the equatorial plane are similar [Re–S(1)=2.2794(18), Re–S(2)=2.2824(18) Å], while for the Re–S axial bond there is an expected lengthening [Re–S(3)=2.3097(19) Å] [24,31,41–52]. The rhenium atom is situated 0.0817 Å, above the equatorial plane of the trigonal bipyramid in the direction of the monothiol. This distance is within the range reported for five-coordinate Re/Tc(V) complexes with similar distorted trigonal bipyramidal geometry [31].

Fig. 1.

A view of the structure of [ReO{η³-(SCH₂CH₂)₂N(CH₂C₆-H₅)}(η¹-C₆H₄Br-4-S)] (1), showing the atom-labeling scheme and 50% thermal ellipsoids.

Table 2.

Comparison of selected bond angles ^a for the rhenium-mixed thiolate complexes of this study

Angle	1	2	3	4	5	6	7	9	10
O(1)–Re–N(1)	96.3(2)	93.9(2)	93.71(13)	93.10(18)	94.60(14)	94.47(17)	96.23(14)	97.41(10)	97.8(2)
O(1)–Re–S(2)	118.23(17)	121.6(2)	122.19(11)	118.37(14)	117.24(12)	119.65(13)	118.12(11)	117.78(9)	117.36(16)
N(1)–Re–S(2)	83.31(15)	84.01(18)	83.97(9)	84.09(12)	84.50(10)	83.11(11)	83.58(10)	83.57(8)	82.86(14)
O(1)–Re–S(1)	120.07(17)	118.6(2)	118.14(11)	122.05(14)	122.55(12)	117.31(13)	118.15(11)	117.55(9)	117.34(16)
N(1)–Re–S(1)	83.80(15)	83.86(18)	83.77(9)	83.63(12)	83.16(10)	83.71(11)	83.90(11)	83.46(7)	83.43(14)
S(2)–Re–S(1)	121.23(7)	119.05(8)	118.94(4)	118.74(5)	119.60(4)	122.21(5)	123.26(4)	124.27(3)	124.84(6)
O(1)–Re–S(3)	105.66(17)	102.8(2)	102.86(10)	102.89(14)	103.53(10)	105.62(13)	104.07(11)	104.65(8)	105.22(16)
N(1)–Re–S(3)	157.91(15)	163.35(17)	163.43(9)	164.00(12)	161.85(10)	159.56(12)	159.42(10)	157.78(7)	156.50(14)
S(2)–Re–S(3)	84.05(7)	87.34(8)	87.28(4)	88.03(5)	87.83(4)	90.02(5)	83.86(4)	88.44(3)	82.34(6)
S(1)–Re–S(3)	87.37(7)	87.97(8)	88.21(4)	88.03(5)	86.39(4)	83.75(5)	89.45(4)	84.03(3)	90.19(6)

^aAngles reported in degrees with e.s.d. values in parentheses.

The compounds [ReO{η³-(SCH₂CH₂)₂N(CH₂C₅-H₄N)}(η¹-C₆H₄X-4-S)] (X = Br (2), Cl (3), F (4), OCH₃ (5)), [ReO{η³-(SCH₂CH₂)₂N(CH₂C₅H₄N)}(η¹-C₆H₄O-CH₃-4-CH₂S)] (6), [ReO{η³-(SCH₂CH₂)₂N(CH₂CH₂-C₅H₄N)}(η¹-C₆H₄X-4-S)] (X = Br (7), Cl (8), OCH₃ (9)), and [ReO{η³-(SCH₂CH₂)₂N(CH₂CH₂C₅H₄N)}(η¹-C₆H₄Cl-4-CH₂S)]·0.5CH₃(CH₂)₄CH₃ (10) are structurally similar to 1 with the exception of the para-substituent of the benzenethiol or benzylmercaptan, as well as the substitution on the nitrogen of the tridentate. The core geometry of the five-coordinate oxo-rhenium complexes containing the tridentate ligand, [(HSCH₂CH₂)₂N(CH₂C₅H₄N)], is shown in Fig. 2 for [ReO{η³-(SCH₂CH₂)₂N(CH₂C₅H₄N)}(η¹-C₆H₄Br-4-S)] (2) and is seen to consist of distorted trigonal bipyramidal geometry with the oxo group and the sulfur atoms of the [SNS] ligand defining the equatorial plane and the axial positions occupied by the sulfur atom of the monothiol and the nitrogen atom of the [SNS] ligand. The angles between the atoms in the equatorial plane are close to the ideal 120° (Table 2), but a value of 163.35(17)° observed for the N(1)–Re(1)–S(3) angle indicates a distortion of the trigonal bipyramid, which can also be seen in the value of the trigonality index [51], τ=0.74. The Re=O bond length is found to be 1.695(6) Å and the Re–N bond length [Re–N(1)=2.221(7) Å] is typical for the Re–N_amine single bond in which the nitrogen atom exhibits sp³ hybridization. The metal–sulfur bond lengths in the equatorial plane are unexceptional [Re–S(1)=2.270(2), Re–S(2)=2.281(2) Å], while the Re–S(3) axial bond length is 2.313(2) Å, a lengthening phenomena noted by others [24,31,41–52]. The rhenium atom is situated 0.0977 Å, above the equatorial plane of the trigonal bipyramid in the direction of the monothiol.

Fig. 2.

A view of the structure of [ReO{η³-(SCH₂CH₂)₂-N(CH₂C₅H₄N)}(η¹-C₆H₄Br-4-S)] (2), showing the atom-labeling scheme and 50% thermal ellipsoids.

Similarly, the core geometry of the five-coordinate oxo-rhenium complexes containing the [(HSCH₂-CH₂)₂N(CH₂CH₂C₅H₄N)] tridentate is shown in Fig. 3 for [ReO{η³-(SCH₂CH₂)₂N(CH₂CH₂C₅H₄N)}(η¹-C₆-H₄Br-4-S)] (7) and is also seen to consist of distorted trigonal bipyramidal geometry. The oxo group and the sulfur atoms of the [SNS] ligand define the equatorial plane, while the axial positions are occupied by the sulfur atom of the monothiol and the nitrogen atom of the [SNS] ligand. The angles between the atoms in the equatorial plane are close to the ideal 120° (Table 2), likewise, a value of 159.42(10)° observed for the N(1)–Re(1)–S(3) angle indicates a distortion of the trigonal bipyramid, which can also be seen in the value of the trigonality index [40], τ=0.60. The Re=O and Re–N_amine bond lengths are typical for this particular class of compounds and are found to be 1.694(3) and 2.217(4) Å respectively [24,31,39–49,53]. As in the previous cases, the metal–sulfur bond lengths in the equatorial plane are unexceptional [Re–S(1)= 2.2758(12), Re–S(2)=2.2918(11) Å], while the Re–S(3) axial bond length is slightly lengthened to 2.3144(11) Å. The rhenium atom is situated 0.0811 Å above the equatorial plane of the trigonal bipyramid in the direction of the monothiol.

Fig. 3.

A view of the structure of [ReO{η³-(SCH₂CH₂)₂-N(CH₂CH₂C₅H₄N)}(η¹-C₆H₄Br-4-S)] (7), showing the atom-labeling scheme and 50% thermal ellipsoids.

In all the oxo-rhenium benzenthiolates and benzylmercaptans (compounds 2–7, 9, 10) the equatorial plane is defined by the two sulfur donors of the tridentate [SNS] ligand and the oxo group, while the sulfur atom of the monothiol and the nitrogen atom of the [SNS] ligand occupy the axial positions. The Addison τ indices for the rhenium mixed thiolate compounds of this study are listed in Table 3, revealing that compounds 1–7, 9 and 10 actually tend to lie closer to the distorted trigonal bipyramidal structure, a result that is similar to other compounds that are members of the oxo-rhenium ‘3+1’ [SNS]/[S] mixed-thiolate family [28–31].

Table 3.

The τ index for the five-coordinate rhenium complexes of this study, as a measure of geometric distortion from idealized geometries

Compound	αa	βb	τc
[ReO{SN(R1)S}(η1-C6H4Br-4-S)] (1)	121.23(7)	157.91(15)	0.61
[ReO{SN(R2)S}(η1-C6H4Br-4-S)] (2)	119.05(8)	163.35(17)	0.74
[ReO{SN(R2)S}(η1-C6H4Cl-4-S)] (3)	118.94(4)	163.43(9)	0.74
[ReO{SN(R2)S}(η1-C6H4F-4-S)] (4)	118.74(5)	164.00(12)	0.75
[ReO{SN(R2)S}(η1-C6H4OCH3-4-S)] (5)	119.60(4)	161.85(10)	0.70
[ReO{SN(R2)S}(η1-C6H4OCH3-4-CH2S)] (6)	122.21(5)	159.56(12)	0.62
[ReO{SN(R3)S}(η1-C6H4Br-4-S)] (7)	123.26(4)	159.42(10)	0.60
[ReO{SN(R3)S}(η1-C6H4OCH3-4-S)] (9)	124.27(3)	157.78(7)	0.56
[ReO{SN(R3)S}(η1-C6H4Cl-4-CH2S)] (10)	124.84(6)	156.50(14)	0.53

^aα ≡ the second largest basal angle.

^bβ ≡ the largest basal angle.

^cτ ≡ (β−α)/60. SN(R)S=η³-{(SCH₂CH₂)₂N(R)} (R₁ = CH₂C₆H₅; R₂ = CH₂C₅H₄N; R₃ = (CH₂)₂C₅H₄N).

In all cases, one equatorial position is occupied by a terminal oxo-group with a typical Re=O distance ranging from approximately 1.69–1.71 Å. The two other equatorial positions are occupied by the two sulfur donors of the [SNS] tridentate. In the complexes of this study, the displacement of Re site from the equatorial plane in the direction of the monothiol group is approximately 0.0753–0.1087 Å as shown in Table 4. The Re–N_amine distances range from 2.21 to 2.23 Å while the sulfur distances are all fairly unexceptional, ranging from 2.27 to 2.32 Å well within the range of those reported previously [52–54]. Tables 2 and 4 compare the relevant bond angles and lengths for compounds 1–7, 9 and 10, respectively.

Table 4.

Comparison of selected bond lengths ^a for rhenium-mixed thiolate complexes

Complex	Re=O	η1-Thiolate	η3-Donor [S(1)–N(1)–S(2)]			ΔReb
		Re–S(3)	Re–S(1)	Re–N(1)	Re–S(2)
1	1.699(5)	2.3097(19)	2.2794(18)	2.208(6)	2.2824(18)	0.0817
2	1.695(6)	2.313(2)	2.270(2)	2.221(7)	2.281(2)	0.0977
3	1.702(3)	2.3087(10)	2.2821(10)	2.229(3)	2.2757(10)	0.1011
4	1.705(4)	2.3074(14)	2.2793(13)	2.231(5)	2.2772(14)	0.1087
5	1.697(3)	2.3119(11)	2.2876(11)	2.234(4)	2.2704(11)	0.0926
6	1.707(4)	2.2983(15)	2.2766(14)	2.215(5)	2.2929(14)	0.1084
7	1.694(3)	2.3144(11)	2.758(12)	2.217(4)	2.2918(11)	0.0811
9	1.703(2)	2.3189(8)	2.2889(9)	2.220(3)	2.3189(8)	0.0753
10	1.688(5)	2.2954(15)	2.2875(15)	2.226(5)	2.2962(16)	0.0815

^aDistances reported in Å with e.s.d. values in parentheses.

^bΔRe, distance of the Re from the least square plane of the equatorial donors.

4. Conclusions

Exploitation of the thiolate chemistry of the oxo-rhenium(V) core has allowed the preparation of a series of mononuclear oxo-rhenium-mixed thiolate complexes. We have demonstrated that the action of the tridentate [SN(R)S] aminodithiol ligand on a suitable {ReO}³⁺ precursor in the presence of a monodentate ligand gives rise to stable, neutral oxo-rhenium complexes of the ‘3+1’ type. This route appears to be a quite general, facile method for moderate yield synthesis of materials with the [ReO{SN(R)S}(S)] core. The geometry and charge of the monodentate thiol ligand may be manipulated easily to produce complexes of various size, shape and charges for clinical development.