Luca Rigamonti

The substituents in 2,6‐bis(2‐R‐2 H ‐tetrazol‐5‐yl)pyridyl neutral ligands R 2 btp (R=Me, t Bu) revealed a prominent effect when reacting with iron(II) salts, in combination with the nature of the anion. According to metal:ligand molar ratio, reaction of R 2 btp with FeCl 2 led to isolate [Fe II (R 2 btp‐κ 3 N,N’,N” ) 2 ](Fe III Cl 4 ) 2 , R=Me ( 1 a ) and t Bu ( 2 a ), where the octahedral iron(II) centres bring two tridentate ligands in mer coordination mode, but also [Fe II ( t Bu 2 btp‐κ 3 N,N’,N” )( t Bu 2 btp‐κ N ) 2 (H 2 O‐κ O )](Fe III Cl 4 ) 2 ( 2 b ), where one ligand is tridentate, while the other two coordinate the iron(II) through one tetrazolyl nitrogen atom, and the octahedral sphere is completed by one water molecule. In all cases, half of the iron ions are oxidised to iron(III) forming the paramagnetic tetrachloroferrato counterions. Reaction of t Bu 2 btp with Fe(ClO 4 ) 2 ⋅ 6H 2 O led to the octahedral [Fe II ( t Bu 2 btp‐κ 3 N,N’,N” ) 2 ](ClO 4 ) 2 ⋅ 4DCM ( 4 a ⋅ 4DCM), which shows solvent‐dependent spin crossover behaviour: while 4 a ⋅ 4DCM is blocked in the high spin state, its unsolvated form, 4 a , undergoes spin transition to low spin in two subsequent steps at 206 K, with opening of a 23‐K hysteresis ( T 1/2↓ =194 K, T 1/2↑ =217 K), and at 136 K ( T 1/2↓ =135 K, T 1/2↑ =137 K). The magnetic profile changes to an incomplete spin transition when the sample absorbs water molecules yielding 4 a ⋅ 1.5H 2 O.

With the clear need for better cancer treatment, naturally occurring molecules represent a powerful inspiration. Recently, curcumin has attracted attention for its pleiotropic anticancer activity in vitro, especially against colorectal and prostate cancer cells. Unfortunately, these encouraging results were disappointing in vivo due to curcumin’s low stability and poor bioavailability. To overcome these issues, herein, the synthesis of eight new pyrimidine–curcumin derivatives is reported. The compounds were fully characterized (1H/13C NMR (Nuclear Magnetic Resonance), LC-MS (Liquid Chromatography-Mass Spectrometri), UV-Vis spectroscopy), particularly their acid/base behavior; overall protonation constants were estimated, and species distribution, as a function of pH, was predicted, suggesting that all the compounds are in their neutral form at pH 7.4. All the compounds were extremely stable in simulated physiological media (phosphate-buffered saline and simulated plasma). The compounds were tested in vitro (48 h incubation treatment) to assess their effect on cell viability in prostate cancer (LNCaP and PC3) and colorectal cancer (HT29 and HCT116) cell lines. Two compounds showed the same anti-proliferative activity as curcumin against HCT116 cells and improved cytotoxicity against PC3 cells.