Novel ferrocene-pyrazolo[1,5-a]pyrimidine hybrids: A facile environment-friendly regioselective synthesis, structure elucidation, and their antioxidant, antibacterial, and anti-biofilm activities

Abstract

It was observed that when two prominent bioactive compounds fused together, the new hybrid showed much more promising possessions. Aiming this, here we have fused pyrazolo[1,5-a]pyrimidines with ferrocene, both of which are popularly known as the bio-active molecular core, employing a very simple and facile synthetic strategy using a mild acid KHSO₄ as a catalyst under ultrasonic irradiation. The structures of these synthesized novel compounds were confirmed by their spectral and analytical data. The single-crystal X-ray crystallographic analysis of a selected compound reveals that the 7-ferrocenyl-pyrazolo[1,5-a]pyrimidine (C₂₂H₁₆ClFeN₃) hybrid interestingly exists as a dimer and forms a triclinic crystal system with P₁ space group (no. 2), a = 7.554(3) Å, b = 13.650(6) Å, c = 18.444(8) Å, α = 96.938(7)^o, β = 90.034(7)^o, γ = 106.015(6)^o, V = 1813.5(14) ų, Z = 4, µ(MoKα)= 0.990 mm⁻¹, wavelength = 0.71073 Å, D_calc = 1.515 g/cm³ with 42808 measured reflection (4.452° ≤ 2θ ≤ 58.312°), 9524 unique reflections (R_int = 0.1267, R_sigma = 0.1390) were used in all the calculations. The final R₁ obtained was 0.0570 (I>2σ(I)) with wR₂ = 0.1656 for all data. Most of the compounds exhibited encouraging antioxidant activities like compounds 3b-c, 3k-l and 3n exhibited prominent nitric-oxide scavenging activities, while compounds 3a-d, 3g, 3k, 3n, and 3o are promising DPPH-scavengers. Compounds 3i-k and 3m exhibited antibacterial activities at MIC of 500 µg/mL, while 3p exhibited activities at MIC of 250 µg/mL. Five of the compounds, 3i-k, 3m, and 3p, were found to possess anti-biofilm activities against both Gram-positive and Gram-negative bacteria.

Graphical abstract

Synopsis: Novel ferrocene-pyrazolo[1,5-a]pyrimidine hybrids were synthesized and investigated for their anti-oxidant, anti-bacterial and anti-biofilm properties. Almost all of the new compounds mentioned have anti-oxidant capabilities and a few of them also exhibited anti-bacterial and anti-biofilm properties