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The three ligands showed relatively good cytotoxicity with IC 50 values ranging from 10±2 to 16±1 µM, while the cytotoxicity of the rhenium complexes was less with IC 50 values ranging from 26±1 to 38±1 µM. Similar results have been reported before, where the presence of the metal appears to show a dilutive effect on the cytotoxicity of the ligand. This makes these complexes ideal for use as theranostic agents, since the ligand provides cytotoxicity, while a radioactive metal center can offer diagnostic properties. [Display omitted] The synthesis, characterisation, crystal structures and cytotoxicity against HeLa cells of three rhenium complexes fac -[Re(CO) 3 (PMA)]+ (PMA = bis(2-pyridylmethyl)amine), fac -[Re(CO) 3 (PMAEth)]+ (PMAEth = bis(2-pyridylmethyl)-2-aminoethanol), and fac -[Re(CO) 3 (PMAProp)]+ (PMAProp = bis(2-pyridylmethyl)-2-aminopropanol) are reported. The tripodal ligands showed slightly higher cytotoxicity than the coordinated complexes with IC 50 values ranging from 10 µM to 38 µM. These values, together with the fact that the ligand backbones can be easily modified to introduce higher toxicity, supports the possible use of Rhenium(I) as a theranostic radiopharmaceutical. [ABSTRACT FROM AUTHOR]

Two bidentate PNP ligands N,N-bis(di-p-tolylphosphino)cyclohexylamine (Cy-pTolPNP) (1) and N,N-bis(di-p-tolylphosphino)cyclobutylamine (Cb-pTolPNP) (2) were synthesized and crystallized. Coordination to the fac-[MI(CO)3]+ core (M = Re, 99Tc) yielded fac-[Re(Cy-pTolPNP)(CO)3Br] (1A), fac-[99Tc(Cy-pTolPNP)(CO)3Cl] (1B), fac-[Re(Cb-pTolPNP)(CO)3Br] (2A) and fac-[99Tc(Cb-pTolPNP)(CO)3Cl] (2B) in relatively good yields (56 to 86%): The structures of 1, 2, 1A and 1B were studied by single crystal X-ray crystallography. Preliminary mitochondrial/antimicrobial evaluation of the free ligand (N,N-bis(di-p-tolylphosphino)-cyclohexylamine) (1) and its respective fac-[Re(CO)3]+ (1A) complex indicates that neither the free ligand nor the complex was active against selected fungi Eremothecium ashbyii and Nadsonia fulvescens. In addition, all four compounds were found to have no activity against Gram-positive and Gram-negative bacterial species. These biological results are essential to the understanding of how these types of complexes behave and show they are perfectly stable in the evaluated bio-environments. The results also indicate that these ligands and complexes may present themselves as excellent models for radiotoxicity studies using technetium-99m, but more specifically, rhenium Re-186 and Re-188. [ABSTRACT FROM AUTHOR]

Rhenium(I) di- and tri-carbonyl complexes of the form fac-[Re(CO)3(L,L′-Bid)X] and [Re(CO)2(L,L′-Bid)X2], where X = aqua (H2O), methanol (CH3OH), triphenylphosphine (PPh3), 1,3,5-triaza-7-phosphaadamantane (PTA), tricyclohexylphosphine (PCy3) and L,L′-Bid = O,O′ bidentate ligands (tropolone = TropH and 3-hydroxyflavone = FlavH) and N,O bidentate ligands (8-hydroxyquinoline = QuinH, 5,7-chloro-8-hydroxyquinoline = diCl-QuinH and quinoline-2,4-dicarboxylic acid = QuinH2), were synthesized and unambiguously characterized by 1H-, 13C-and 31P-NMR, IR, UV/Vis and micro-analysis. The crystal structures of four complexes, namely fac-[Re(CO)3(QuinH)(H2O)]·H2O (5), fac-[Re(CO)3(Quin)(PPh3)] (11), fac-[Re(CO)3(diCl-Quin)(PPh3)] (12) and [Re(CO)2(Trop)(PPh3)2]·2C6H5CH3 (20) were obtained. Re–P bonding distances for 11 and 12 are 2.4948(8) and 2.4908(8) Å, respectively, indicating the effect of the electron-withdrawing substituents of the diCl-Quin− ligand. The second-order rate constants for the substitutions of methanol at 25.1 °C in fac-[Re(CO)3(L,L′-Bid)(CH3OH)] (L,L′-Bid = Trop, Flav and QuinH) type complexes by different entering phosphine ligands (PPh3, PCy3, and PTA) varied between 7.23(7) × 10−5 and 1.32(3) × 10−3 M−1 s−1 and were found to depend on the coordinated bidentate ligand (in general k1 (QuinH) < k1 (Trop) < k1 (Flav)). The toxicity of fac-[Re(CO)3(QuinH)(PTA)], fac-[Re(CO)3(Trop)(PTA)], fac-[Re(CO)3(Trop)(PPh3)] and fac-[Re(CO)3(Flav)(PPh3)] on the cervical cancer HeLa and epithelial RPE-1 cell lines was then evaluated. Complex fac-[Re(CO)3(Flav)(PPh3)] (16) and fac-[Re(CO)3(Trop)(PPh3)] (13) displayed the highest cytotoxicity with IC50 values of 12.21 ± 0.17 μM and 13.35 ± 0.94 μM, respectively in HeLa cells. Interestingly, a small selectivity towards cancer over non-cancerous cells was observed for these compounds (IC50 = 18.41 ± 3.16 μM and >25 μM in RPE-1 cells). [ABSTRACT FROM AUTHOR]

The synthesis and crystal structures of two new rhenium(I) complexes obtained utilizing benzhydroxamic acid (BHAH) and 3‐hydroxyflavone (2‐phenylchromen‐4‐one, FlavH) as bidentate ligands, namely tetraethylammonium fac‐(benzhydroxamato‐κ2O,O′)bromidotricarbonylrhenate(I), (C8H20N)[ReBr(C7H6NO2)(CO)3], 1, and fac‐aquatricarbonyl(4‐oxo‐2‐phenylchromen‐3‐olato‐κ2O,O′)rhenium(I)–3‐hydroxyflavone (1/1), [Re(C15H9O3)(CO)3(H2O)]·C15H10O3, 3, are reported. Furthermore, the crystal structure of free 3‐hydroxyflavone, C15H10O3, 4, was redetermined at 100 K in order to compare the packing trends and solid‐state NMR spectroscopy with that of the solvate flavone molecule in 3. The compounds were characterized in solution by 1H and 13C NMR spectroscopy, and in the solid state by 13C NMR spectroscopy using the cross‐polarization magic angle spinning (CP/MAS) technique. Compounds 1 and 3 both crystallize in the triclinic space group P with one molecule in the asymmetric unit, while 4 crystallizes in the orthorhombic space group P212121. Molecules of 1 and 3 generate one‐dimensional chains formed through intermolecular interactions. A comparison of the coordinated 3‐hydroxyflavone ligand with the uncoordinated solvate molecule and free molecule 4 shows that the last two are virtually completely planar due to hydrogen‐bonding interactions, as opposed to the former, which is able to rotate more freely. The differences between the solid‐ and solution‐state 13C NMR spectra of 3 and 4 are ascribed to inter‐ and intramolecular interactions. The study also investigated the potential labelling of both bidentate ligands with the corresponding fac‐99mTc‐tricarbonyl synthon. All attempts were unsuccessful and reasons for this are provided. The synthesis and crystal structures of two new rhenium(I) complexes, obtained utilizing benzhydroxamic acid and 3‐hydroxyflavone as bidentate ligands, are reported. Furthermore, the crystal structure of free 3‐hydroxyflavone was redetermined at 100 K in order to compare the packing trends and solid‐state NMR spectroscopy with those of the solvate flavone molecule. [ABSTRACT FROM AUTHOR]

Abstract fac -[Re(OH 2) 3 (CO) 3 ]+ reacts with acetylacetone (AcacH) at room temperature to yield fac -[Re(Acac)(CO) 3 (OH 2)] (1) under aqueous conditions 1 was isolated and reacted with the monodentate ligand, 1,3,5-triaza-7-phosphaadamantane (PTA), to form fac -[Re(Acac)(CO) 3 (PTA)] (2) in a 9:1 ratio of water and methanol. The isolated complex 2 was further reacted with an excess of PTA ligand in a 9:1 ratio of water and methanol to yield the highly soluble cis - trans -[Re(Acac)(CO) 2 (PTA) 2 ] (3). The complexes have been characterized by spectroscopic techniques IR, 1H, 13C and 31P NMR, as well as single crystal X-ray crystallography for 2 and 3. From the crystallographic results of 3 , the formation of the cis - trans conformation was confirmed, while the 31P NMR results further established 3 as the sole product formed. A 31P NMR kinetic study, involving the methanol substitution of fac -[Re(CO) 3 (Acac)(CH 3 OH)] (4) and fac -[Re(CO) 3 (Trop)(CH 3 OH)] (TropH = tropolone) with PTA as entering monodentate ligand was also undertaken. The second-order rate constants (k 1) for the forward reactions at 25.0 °C were respectively obtained as (35.9 ± 0.2) x 10−3 M−1 s−1 and (25.1 ± 0.8) M−1 min−1. In a preliminary 31P NMR kinetic investigation of the carbonyl substitution in fac -[Re(Acac)(CO) 3 (PPh 3)] by PPh 3 , an estimated equilibrium constant (K est) of ≈ 5.09 was calculated for the reversible reaction. Graphical abstract Unlabelled Image Highlights • Dicarbonyl rhenium(I) complex synthesised in 90% water is obtained at 80 °C and above. • Formation of fac -[Re(Trop)(CO) 3 (PTA)] is 700 times faster than corresponding Acac complex. • Equilibrium constant (K est) of 5.09 is obtained in carbonyl substitution kinetics of fac -[Re(Acac)(CO) 3 (PPh 3)] by PPh 3. [ABSTRACT FROM AUTHOR]

Six rhenium(I) complexes are structurally compared, with regards to steric and electronic influences induced by the different β-diketone (benzoylacetone – Benzac, trifluoroacetylacetone – Tfaa and hexafluoroacetylacetone – Hfaa) and phosphine ligands (cyclohexyldiphenyl phosphine – PPh 2 Cy and dicyclohexylphenyl phosphine – PPhCy 2 ). The complexes fac -[Re(Benzac)(CO) 3 (PPh 2 Cy)] ( 2 ), fac -[Re(Benzac)(CO) 3 (PPhCy 2 )] ( 3 ), fac -[Re(Tfaa)(CO) 3 (PPh 2 Cy)] ( 5 ), fac -[Re(Tfaa)(CO) 3 (PPhCy 2 )] ( 6 ), fac -[Re(Hfaa)(CO) 3 (PPh 2 Cy)] ( 8 ) and fac -[Re(Hfaa)(CO) 3 (PPhCy 2 )] ( 9 ) were synthesized by using the ‘2 + 1’ mixed ligand approach and characterized by means of IR, UV–Vis, 1 H, 13 C and 31 P NMR and also X-ray diffraction, clearly showing the increase in the carbonyl stretching frequencies and downfield shifts in the 31 P NMR as the fluoro atoms on the ligand backbone increases. The Tolman angles for the coordinated phosphine ligands are: 2  = 134.77°; 3 molecule A = 146.81°; 5  = 134.46°; 6  = 146.05°; 8  = 136.68° and 9  = 146.22°, illustrating the change in steric bulk as the cyclohexyl ligands on the phosphine ligands increase. A direct link is noted between the Re–P distances (2.4906(6) Å for 2 , 2.5213(17) Å for 3 molecule A, 2.4865(16) Å for 5 , 2.5372(15) Å for 6 , 2.4906(14) Å for 8 and 2.5365(16) Å for 9 ), O,O ′-bidentate ligand bite angles, O4–Re–O5, (85.12(6)° for 2 , 83.34(13)° for 3 molecule A, 84.91(12)° for 5 , 83.53(12)° for 6 , 84.54(11)° for 8 and 83.7(2)° for 9 ) and the calculated dihedral angles (3.677(1)° for 2 , 12.521(1)° for 3 molecule A, 1.489(7)° for 5 , 12.463(11)° for 6 , 2.940(7)° for 8 and 11.747(6)° for 9 ). The dihedral angle is calculated between the equatorial plane (Re1, C1, O1, C2, O2, O4, C5, C6, C7, O5) and the plane through Re1, O4, C5, C6, C7, O5. Dihedral angles of approximately four times larger are observed in complexes with coordinated PPhCy 2 ligands compared to the PPh 2 Cy containing analogues, indicating the steric effect induced on the bidentate ligand by the extra cyclohexyl substituent on the PPhCy 2 ligand. [ABSTRACT FROM AUTHOR]

C29H28O5PRe, triclinic, P¯1 (no.2), a=12.733(7) Å, b=18.668(11) Å, c=24.779(15) Å, α=101.442(20)°, β=100.844(18)°, γ=104.240(19)°, V =5419(9) Å3, Z =8, Rgt(F)=0.0307, wRref(F2)=0.0772, T =100 K. [ABSTRACT FROM AUTHOR]