Self-Assembly and Multifaceted Bioactivity of a Silver(I) Quinolinate Coordination Polymer

Abstract

Coordination polymers have emerged as a new class of potent biologically active agents due to a variety of important characteristics such as the presence of bioactive metal centers and linkers, low toxicity, stability, tailorable structures, and bioavailability. The research on intermediate metabolites has also been explored with implications toward the development of selective anticancer, antimicrobial, and antiviral therapeutic strategies. In particular, quinolinic acid (H₂quin) is a recognized metabolite in kynurenine pathway and potent neurotoxic molecule, which has been selected in this study as a bioactive building block for assembling a new silver(I) coordination polymer, [Ag(Hquin)(μ-PTA)]_n·H₂O (1). This product has been prepared from silver oxide, H₂quin, and 1,3,5-triaza-7-phosphaadamantane (PTA), and fully characterized by standard methods including single-crystal X-ray diffraction. Compound 1 has revealed distinctive bioactive features, namely (i) a remarkable antiviral activity against herpes simplex virus type 1 (HSV-1) and adenovirus 36 (Ad-36), (ii) a significant antibacterial activity against clinically important bacteria (Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa), and (iii) a selective cytotoxicity against HeLa (human cervix carcinoma) cell line. The present work widens a growing family of bioactive coordination polymers with potent antiviral, antibacterial, and antiproliferative activity.

Scheme 1. Simplified Representation for the Self-Assembly Synthesis of 1

Figure 1

Crystal structure of 1. (a) Coordination environment around silver(I) center and ligands connectivity. (b) 1D coordination polymer chain. (c) Topological representation of two adjacent chains of a 2C1 type. (a, b) H atoms and crystallization H₂O were omitted; Ag (magenta), N (blue), P (orange), O (red), C (gray). (c) Ag centers (magenta balls), centroids of μ-PTA linkers (gray).

Figure 2

Oxygen uptake for autoxidation of micellar system initiated with ABAP at 37 °C and pH 7.0. Autoxidation in the absence (ABAP, blank) or presence of tested compounds (1 μM): 1, PTA, or H₂quin. Final concentration: LinMe 2.74 mM, Triton X-100 8 mM.

Figure 3

Fluorescence emission spectra in the HSA–1 system. Lines a–i correspond to the ratios of [HSA]:[Ag] = 1:0–1:16 (λ_ex = 280 nm, 310 K, pH 7.40).

Figure 4

Stern–Volmer plots of the HSA–1 system at 310 and 298 K (λ_ex = 280 nm) (inset: log((F₀ – F)/F) vs log [Q] plots under the same conditions).