Synthesis and Characterization of Novel [2 + 1] Tricarbonyl Rhenium Complexes with the Hydrophilic Phosphine Ligands PTA and CAP

Abstract

In the pursuit of hydrophilic model fac-[Re(CO)₃]⁺ complexes for (radio) pharmaceutical applications, six novel [2 + 1] mixed-ligand complexes of the general type fac-[Re(CO)₃(bid)P] were synthesized and characterized, where bid is a bidentate ligand bearing either (N, O) or (S, S') donor atom sets and P is the hydrophilic phosphine 1,3,5-triaza-7-phosphoadamantane (PTA) or its macrocyclic homologue 1,4,7-triaza-9-phosphatricyclo[5.3.2.1]tridecane (CAP). The (N, O) ligands used in this study were picolinic and quinaldic acid, while the (S, S') ligand was diethyldithiocarbamate. The complexes were synthesized in generally high yields and purity and the characterization was performed by spectroscopic methods, IR, NMR, and elemental analysis. Detailed X-ray crystallographic study of molecular packing by using Hirshfeld analysis tools revealed a plethora of intermolecular interactions such as hydrogen bond, π⋯π, C-H⋯π, and carbonyl-carbonyl interactions. To our knowledge, the CAP complexes reported herein are the first example of [2 + 1] mixed-ligand fac-[Re(CO)₃]⁺ complexes with CAP. The new complexes might have the potential to serve as platforms for the design of target-specific complexes with favorable pharmacokinetics.

Scheme 1

Synthesis of complexes 1a-3a and 1b-3b. Reactions and conditions: (a) quinH, H₂O, 60°C, 1 h; (b) X, MeOH, reflux, 2 h; (c) picH, H₂O, 70°C, 3 h; (d) X, MeOH, reflux, 2 h; (e) Et₂SS, X MeOH, reflux, 2 h.

Figure 1

Partially labelled plots of 1b (a) and 2b (b).

Figure 2

Partially labelled plots of 3a (a) and 3b (b).

Figure 3

Intermolecular interactions observed in the structure of compound 1b. Dashed thick dark green (antiparallel C₃-O₃⋯C₃-O₃) and dark red lines indicate carbonyl-carbonyl interactions (C-O₅⋯C₁-O₁). Dark violet dashed lines indicate C₁₉-H₁₉⋯π interactions. Light green dashed lines indicate π⋯π between quinaldic ligands and orange dashed lines indicate C₁₈-H₁₈A⋯O₂, C₁₄-H₁₄B⋯O₂ and C₉-H₉⋯O₅ hydrogen bonds.

Figure 4

(a), (b) Different views of the dnorm decorated HS, (c) two views of the shape decorated HS, and (d) fingerprint plot for the 1b complex. A1, A2, A3 and B1, B2, B3 are the donor and acceptor contact points of C₁₈-H₁₈(A)⋯O₂, C₁₄-H₁₄(B)⋯O₂, C₉-H₉⋯O₅ hydrogen bond interactions. The green ellipse in (a) indicates the area of antiparallel CO⋯CO, C₃≡O₃ carbonyl interactions. E1, E2 and D1, D2 are the donor and acceptor contact points involved in the M-C⋯CO, O₅⋯C1‴ type of interactions. The white and orange ellipses in (c) indicate π⋯π and C-H⋯π (F1 and G1 are donor and acceptor contact points, respectively, Table 5) type of interactions.

Figure 5

Intermolecular interactions among neighboring clusters in the structure of compound 2b. The different type of hydrogen bond interactions is indicated with dashed thick orange (C₁₂-H₁₂⋯O₂), dark red (C₁₄-H₁₄A⋯O₅ and C₁₅-H₁₅B⋯O₅ pairs of interactions), and cyan (C₈-H₈⋯O₄) dashed lines. The pink dashed lines indicate carbonyl C₈-H₈⋯C₁ type of interactions. C₆-H₆⋯O₅, C₉-H₉⋯O₁ and C₁₆-H₁₆∙∙∙Cg₂ (C-H⋯π type of interactions) are indicated with violet, yellow, and dark green dashed lines, respectively.

Figure 6

(a) Different views of the d_norm decorated HS, (b) two views of the shape decorated HS and (c) fingerprint plot for the 2b complex. A1, A2, A3, A4, A5, A6 and B1, B2, B3, B4, B5, B6 are the donor and acceptor contact points of C₁₂—H₁₂B⋯O₂, C₁₄—H₁₄A⋯O₅, C₁₅—H₁₅A⋯O₅, C₆—H₆⋯O₅, C₈—H₈⋯O₄ and C₉—H₉⋯O₁ hydrogen bond interactions. E1, E2 and D1, D2 are the donor and acceptor contact points involved in the C₁₃-H₁₃⋯Cg₂ and C₁₆-H₁₆···Cg₂ C-H⋯π type of interactions. E3 and D3 are the donor and acceptor contact points of C₈-H₈⋯C₁ type of interactions.

Figure 7

Stacking of layers along the c crystallographic axis in the structure of compound 3a. Braces indicate the position of layers and arrows the carbonyl-carbonyl interactions. The dashed thick orange lines indicate C₉-H₉A⋯N₄ and C₉-H₉B⋯N₃ and the dark red one indicates C₁₃-H₁₃A⋯O₁ hydrogen bonds. Dashed thick dark green lines indicate antiparallel CO⋯CO carbonyl-carbonyl interactions. Details for the arrangement of complexes and the intermolecular interactions within the layer are presented in Figure S3.

Figure 8

(a), Different views of the d_norm decorated HS and (b) fingerprint plot for the 3a complex. A1, A2, A3 and B1, B2, B3 are the donor and acceptor contact points of C₉—H₉(A)⋯N₄, C₉—H₉(B)⋯N₃ and C₁₃—H₁₃A⋯O₁(indicated with orange arrows in fingerprint plot) hydrogen bond interactions (Table 5). Label D indicates the area of antiparallel CO⋯CO, C₃≡O₃ carbonyl interactions. Red arrows in the fingerprint plot indicate the C⋯H/⋯C contact points.

Figure 9

Stacking of layers along the b crystallographic axis in the structure of compound 3b, The dashed thick orange, dark red, and cyan lines indicate C₈-H₈A⋯O₂, C₅-H₅⋯S₂ and C₆-H₆B⋯N₂ hydrogen bonds, respectively. Details for the arrangement of complexes and the intermolecular interactions within the layer are presented in Figure S4.

Figure 10

(a) Different views of the d_norm decorated HS and (b) fingerprint plot for the 3b complex. A1, A2, A3 and B1, B2, B3 are the donor and acceptor contact points of C₈-H₈A⋯O₂, C₅-H₅A∙∙S₂ and C₆-H₆B⋯N₂ hydrogen bond interactions (Table 5).