Chemosensitivity studies havebeen conducted against human pancreatic carcinoma (MIA PaCa-2), humancolorectal adenocarcinoma p53-wildtype (HCT116 p53+/+) and normal human retinal epithelial celllines (APRE-19). The most active complex, which contains a 2-furan-substitutedligand (4), is 5x more cytotoxic than the analogs 3-furancomplex (5) against MIA PaCa-2. Several complexes werescreened under hypoxic conditions and at shorter-time incubations,and their ability to damage DNA was determined by the comet assay.Compounds were also screened for their potential to inhibit the growthof both bacterial and fungal strains.The synthesis and characterization of 24 ruthenium(II)arene complexesof the type [( Tuning the ligand environment andmetal oxidation states can help control the thermodynamic and kineticproperties of the complexes in order to control their biological activity.3 Therefore, ruthenium research has produced aplethora of potential therapeutics with a wide range of structures,geometries, and oxidation states and easily tunable ligand environments.Ruthenium is relatively well toleratedby the body,5 andthis stemmed from the promising cytotoxicity of Ru(III) compoundsNAMI-A (ImH)[trans-RuCl4(DMSO)(Im)] (trans-RuCl4(Ind)2], Ind = indazolium) (6 Such ruthenium complexeshave different modes of action than cisplatin (CDDP), including theability to target cancer cells that are resistant to platinum treatment.7Over the last two decades, there has been a surge in anticancerresearch for ruthenium coordination compoundsazolium) 1B.6 Such0/+  RuCl(en)][PF6] (RM175),9 which has multiple binding modes to nucleic acids,10l-cysteine, and methionine.11 Complexes were inactive with N,O-chelating ligands, whereascomplexes containing an O,O-chelating acetylacetone  arene complexes with different ligand-bindingmodes whereby β-ketoiminate N,O-bound ligands are considerablymore effective than N,N-picolinamide and O,O-acetylacetone-type ligandsfollowing the trend N,O > N,N > O,O.14To date, Ru(II) organometallic “piano stool”complexesof the type [(arene)RuX(L)]ligand) 1Cmake u16 Ferrocenyl-based compounds can act as “redox antennas”,aiding in the formation of reactive oxygen species (ROS) and leadingto DNA damage.17 We have recently shownthat the incorporation of ferrocene into β-diketonate ligandsto synthesize functionalized ferrocenyl β-diketonate ligands2(Fc-acac)Ru][PF6]  and human colorectalcarcinoma p53-wildtype (HCT116 p53+/+) cell lines with dose-dependent double-strand DNAdamage, which is correlated to their cytotoxicity.Heterobimetallic species have the potentialbenefit of both metalsworking together, and by combining ruthenium and ferrocene into asingular complex, it is possible to have synergistic effects againstcancer cells.p-cymene (p-cym) or 1,2,3,4,5-pentamethylcyclopentadiene(Cp*) and Fc-acac = a functionalized ferrocenyl β-diketonateligand with either a methyl or trifluoromethyl group  piano-stool complexesof the type [(arene)RuCl(Fc-acac)], where arene = yl group 1G.22 The1 and 7).22 This includes the analysis of 21 new molecular structures via single-crystalX-ray diffraction (sc-XRD). All compounds have been screened for theircytotoxic potential using the MTT assay against MIA PaCa-2 and HCT116 p53+/+ cancer cell lines and a normal human retinalepithelium cell line, ARPE-19. Additional studies were conductedon the ligand and complex stability by NMR spectroscopy, intracellularmetal uptake by ICP-MS, cyclic voltammetry to assess accessible redoxpotentials, cytotoxicity under severe hypoxic (0.1% O2)conditions at shorter exposure times, and double-strand breakages(DSB) of DNA using the comet assay. The compounds have also been screenedfor their potential to inhibit the growth of several bacterial andfungal strains.We have extendedthe library of Ru(II) piano-stool complexes toinclude 22 new complexes and the two recently reported complexes byManikandan et al. . The p-cymene Ru(II) ferrocenyl β-diketonatecomplexes, [(p-cym)RuCl(Fc-acac)] 1–24, were preparedby adaptations of previously published methods,14 whilst 1 and 7 have been recentlyreported.22 A functionalized ferrocenylβ-diketonate ligand (2 eq.) was stirred at room temperatureovernight with triethylamine (2 eq.) and [(p-cym)RuCl2]2 (1 eq.) in dichloromethane RuCl(Fc-acac)] complexes have ashift in the ferrocenyl protons to lower frequencies. Due to the introductionof a chiral center and a loss of symmetry caused by the restrictedrotation of the top Cp ring , the resonances for free ligand appear as two 2H broad triplets(ca. 4.75 and 4.50 ppm) which move to two 1H doubletof triplets (ca. 4.80 and 4.58 ppm) and two 1H tripletof doublets (ca. 4.35–4.30 ppm).The ferrocenyl β-diketonateligands (Fc-acac) were synthesized using a Claisen condensation reactionand our previously reported literature methods.f 23–97% S1. The pL5, L8, L11, L13, L14, and L23  were obtained from slow evaporationof acetonitrile. Molecular structures were determined by sc-XRD analysis(Tables S1 and S2) with structural solutionsperformed in a tetragonal (L5), monoclinic (L8 and L13 and L14), orthorhombic (L11), or tetragonal (L23) space groups. All moleculesdisplay a planar structure with angles of 119–122° aroundthe enol/keto center (Tables S3 and S4)and the ferrocenyl group adopts an eclipsed geometry, as discussedin our previous work.18 In all cases, intramolecularhydrogen bonding is observed between enol–keto with O–H···Odistances ranging between 2.46 and 2.50 Å (D–A), thusrestraining the geometry to a planar orientation.Red/orangesingle crystals of ligands 1, 2, 4–6, and 9–24  wereobtained from either the slow evaporation of acetonitrile or the vapordiffusion of dichloromethane/pentane at 4 °C. Sc-XRD analysis(Tables S5–S10) was obtained, andsolutions were performed in monoclinic cells except for complexes 6 (orthorhombic) and 16 (triclinic). All rutheniumarene complexes adopt the expected pseudo-octahedral“piano stool” geometries with the angles around theruthenium metal center in the range of 84–89° (Tables S11 and S12). Intramolecular interactions(D···A = 3.4–4.0 Å) are seen between the p-cymene isopropyl group and the chloride bound to the rutheniumcenter (C10/11–H···Cl1) in all cases (except 6) with additional intermolecular interactions (D···A= 3.2–4.0 Å) observed in all complexes. These interactionscould explain the shift to a lower frequency for the p-cymene hydrogens, which was also observed in our previous arene-Ru(II)work.14Red/orangesingle crystals of complexes 1–24, cisplatin (CDDP),carboplatin (CARB), and oxaliplatin (OXA) using a 96 h MTT assay (Table S13). All compounds were screened againsthuman pancreatic carcinoma (MIA PaCa-2) and human colorectal adenocarcinoma p53-wildtype (HCT116 p53+/+).The results show that complexes display varying cytotoxicity towardboth cancer cell lines tested with a general increase in activityobserved against MIA PaCa-2. The 2-furan Fc-acac complex 4 exhibited the highest cytotoxicity  against MIA PaCa-2 followedby the trifluoromethyl Fc-acac complex 7 (IC50 = 11 ± 1 μM). Although 4 exhibits the highestIC50 value against MIA PaCa-2, it has a significantly lowerpotency than the Ru(II) coordination analogues we have previouslyreported .21To deduce any structural–activityrelationships (SARs), chemosensitivity studies were performed forcomplexes 1, which contains an unfunctionalizedFc-acacligand, has low activity against all cell lines (IC50 =92–93 μM), and highlights that functionalizing the methylwith electron-withdrawing groups improves the cytotoxicity. The additionof a phenyl substituent (2) increases the activity byca. 2-fold against MIA PaCa-2 (IC50 = 50 ± 6 μM);however, by increasing the hydrophobicity further from phenyl (2) to naphthyl (3), the IC50 valuesdecrease and complex 3 is inactive against all cell lines(IC50 > 100 μM), confirming that the IC50 values do not correlate with the hydrophobicity. The hydrophobicityof each complex were obtained from an octanol–water shake-flaskmethod, and the data is shown in Table S14. It should be noted that, when comparing the recent work of Manikandanet al., complexes 1 and 7 follow the sametrend22 whereby the activity of 7 > 1. However, their activities are significantlylowerthan those reported against HeLa , A2780 (ovarian) and A2780cisR(cisplatin resistant ovarian). This highlights potential selectivitytoward these cell lines and highlights the need for further screeningof our library against a wider range of cancerous cells.Complex 1–24 (Table S13) wherebyall compounds were non-toxic toward this cell line at the maximumtested concentrations (>100 μM), demonstrating excellentchemoselectivitytoward the cancer cell lines MIA PaCa-2 and HCT116 p53+/+. This contrasts with CDDP and OXA, which remain cytotoxictoward normal cell lines; IC50 = 6 ± 1 μM and3.0 ± 0.3 μM, respectively. The IC50 valueshave been expressed as a selectivity index (SI), which are calculatedby dividing the IC50 value against the normal cell lineby the IC50 value against the cancer cell line (Table S13). SI > 1 indicates selectivity forthe cancer cell line over the normal cell line ARPE-19. Unlike OXA,which is selective for HCT116 p53+/+ (SI= 3.2), complexes 1–24 have low selectivitytoward this cell line with SI values ranging from 1.0 to 2.1. Whenanalyzing the SI values for all complexes against MIA PaCa-2, thereis greater selectivity than both CDDP (SI = 1.7) and OXA (SI = 1.0)with SI values of up to 12.7 for complex 4 . Several changes were observed for all complexes, which includesthe darkening of the samples from red to brown and bathochromic orhypo/hyperchromic shifts. The UV–vis spectra are assigned tentativelyfrom TD-DFT calculations on similar structures.25 In most complexes(except 6 and 7), there is a hyperchromicshift of a newly formed MLCT band in the region of 330–370nm and ligand-based absorbance at 220–230 nm. These changesin the spectral properties of the complexes strongly suggest thatthere are changes to the Ru–Cl bond but they are not conclusive.To assign the structural changes, 1H NMR spectroscopy wasmeasured first in DMSO-d6 and then in90% DMSO-d6/10% D2O . Attemptswere made to increase the water content (>10%) of the samples;however,a significant amount of complex precipitation was observed, affectingthe overall concentrations and impeding a full analysis.To understand the lack of activityin our complexes, the stability has been assessed by UV–visspectroscopy in 10% H1, 2, 4 and 7 and thecorresponding ferrocenyl β-diketonate ligands L1, L2, L4 and L7 were analyzedafter initial (ca. 5 min), 20 and 40 min and then between 1 and 96h at 293 K (ca. 5 mg/mL). On analysis of the ferrocenyl ligands inboth 100% DMSO-d6 and 90% DMSO-d6/10% D2O, complete decompositionis observed by ca. 12 h to give free Cp (6.5 ppm) and a paramagneticspecies. The speed at which decomposition happens is faster in thepresence of 10% D2O. When comparing complexes 1, 2, 4, and 7 to the correspondingligands L1, L2, L4, and L7 after 96 h, the stability of the complexes is enhanced,where although some free Cp is generated, it is slower than the ligandalone.Complexes d6, complexes 2 and 4 are the most stable and do not changeover 96h, whereas complexes 1 and 7 show some decompositionto free p-cymene, which is observed in the new signalsat 7.10, 2.95, 2.22, and 1.16 ppm . When analyzed in the presence of 10% D2O, all complexesdecompose by 96 h to free p-cymene, free Cp, anda paramagnetic species. It should be also noted that, unlike the workreported by Manikandan et al.,22 we donot observe an aqua species, which is likely due to rapid exchange.To further assess this, we have conducted NMR studies of complex 1 in the presence of 100 mM NaCl , and decomposition to free p-cymene and Cp still occurs but to a lower degree.In 100% DMSO-1, 2, 4 and 7 and their corresponding ferrocenyl β-diketonate ligands L1, L2, L4 and L7 havebeen assessed after MIA PaCa-2 cells were treated for 48 h with 10μM of each compound. To understand the cytotoxicity relationships,MTT assays of all compounds were conducted after 48 h of incubation(Table S15). The cytotoxicity of the ligandsfollows the order L7 > L4 > L1 ≈ L2, while the uptake of Fe followsthe oppositetrend whereby L7 has the lowest uptake of 1536 ±202 ng Fe/106 cells (6 cells). The least active ligands L1 and L2 have a higher uptake of 2661 ±974 ng Fe/106 cells and 2524 ± 458 ng Fe/106 cells, respectively.It has been reported that cytotoxicitycan be related to the uptake of compounds into the cell. The uptakeof complexes 4 (IC50 = 23 ± 2 μM)and 7 (IC50 = 30 ± 1 μM) have similaractivity; however, their uptake is very different, suggesting differentmodes of action. Complex 4 has overall the lowest uptakeof 1264 ± 229 ng Fe/106 cells and 281 ± 82 ngRu/106 cells, which is not significant when compared tothe control alone. It should be noted that the uptake of complex 7 (6077 ± 119 ng Fe/106 cells and 8388 ±369 ng Ru/106 cells) is significantly enhanced when comparedto the corresponding ligand, where the intracellular Fe content isincreased by approximately 4-fold. While there is no correlation betweenthe cytotoxicity and uptake of these compounds, the binding of theferrocenyl β-diketonate ligands to the Ru(II) center does increasethe cellular uptake, and this is possibly linked to the complexesincreased stability, which we also observed in the NMR studies.When considering the cytotoxicity of the complexesafter 48 h,complexes + redox couple.17 Totest that the redox potential is within a biological relevant region,cyclic voltammetry (CV) experiments are conducted on complexes 1, 2, 4, and 7 andtheir corresponding ferrocenyl β-diketonate ligands L1, L2, L4, and L7 for reference.All complexes exhibit a rich redox chemistry with several oxidationand reduction peaks in the scanned region between −2.1 and1.65 V . The discussion is focused on the metal-based redoxprocesses, and a full analysis of the CV can be found in the Supporting Information.Ferrocene-containing compounds arewell known to exhibit cytotoxicity due to the formation of ROS, duethe Fe/Fe+ redoxcouple. When compared to ferrocene (0.40 V against SCE), the redoxpotential is shifted to more positive values due to the electron-withdrawingeffect of the β-diketonate functionality, which is in line withpreviously reported ferrocenyl functionalized ruthenium arene complexes.26 Substitution of the methyl group (1) with phenyl (2) or 2-furan (4) has onlya negligible effect on the potential in both the ligands and complexes.However, the introduction of a trifluoromethyl moiety (7) shifts the potential to more positive values in line with its stronglyelectron-withdrawing character. The potentials shift by 0.08 and 0.10V for the ligand and complex, respectively.All compounds exhibit a reversible single-electronoxidation between0.53 and 0.71 V, which is assigned to the Fc*/Fc*7 increases the redox stability of the Ru(II) centerto a higher degree.The CVs of all complexesexhibit an irreversible oxidation in theregion of 1.29–1.48 V with a similar trend as discussed forthe ferrocenyl redox couple assigned to the irreversible oxidationof Ru(II) to Ru(III). Therefore, electronic communication betweenthe substituents on the ferrocenyl β-diketonate ligands andthe Ru center exists; hence, the electron-withdrawing substituentin 27 and hypoxiccellular environments, these are only discussed in the Supporting Information.28 A similar conclusion is drawn for the irreversible Ru(II) to Ru(III)oxidation. In contrast, the reversible Fc*/Fc*+ redox couplesare within a reasonable region to induce ROS, suggesting that sucha mode of action might contribute to the overall cytotoxicity. Nocorrelation between the complexes’ CV’s and their cytotoxicityis found, indicating that other possible modes of actions highly likelycontribute significantly to the overall toxicity.Irreversible reductions tentatively assignedto the ferrocenylβ-diketonate ligands are observed in the region between −1.42and 1.98 V. Since these reductions are too far shifted to lower potentialsto be relevant in both normoxic29 Hypoxic cellsare well known to be resistant toward chemotherapy and radiotherapytreatments, leading to great challenges in finding suitable cancertherapeutics.30 In particular, reducingenvironments associated with hypoxia can cause difficulties for transitionmetals as a change in their oxidation state can lead to a change intheir structure, binding mode, cellular drug uptake, and metabolismand even reduce the effectiveness of their cellular mechanism of actionor change it completely.31Cancer cells have areas with extremelylow oxygen concentrations, which is referred to as hypoxia, whichleads to a reducing environment inside the cells. This environmentis due to the poor formation of new blood vessels during the rapidgrowth phase of the tumor.2). Complexes 4, 7, CDDP, andOXA were screened against MIA-PaCa-2 , and all show a decrease in cytotoxicity, including the clinicallyapproved compounds CDDP and OXA. Complex 7 experienceda 4-fold loss of activity from normoxic to hypoxic conditions ,while CDDP exhibited a significant loss of activity that was >14-fold.All compounds are considered inactive, and this may be due to no accessiblereduction available in the cellular environment. Possible reasonsfor the reduced activity under hypoxic conditions are the absenceof a reduction peak close to −0.241 V against the SCE (0 Vagainst the SHE), ruling out a redox-dependent activation as observedfor other ruthenium compounds like NAMI-A or KP101932 and no targeting of hypoxia-inducible factors as describedpreviously for Ru(II) arene complexes.34 A loss ofsuch activity has also been observed for the clinical platinum complexesCDDP and OXA under hypoxic conditions against a range of cell lines.38The influenceof the oxygen concentration upon the complex’s potency wasassessed after 96 h of MTT assay in severe hypoxic conditions  of DNA with varyingconcentrations of compound was studied after incubation with MIA PaCa-2cells for 48 h. After harvesting the cells, quantification of thelevels of SSB of DNA were assessed by using the alkaline comet assay.Compounds 2 and 7 only show a small degreeof SSB when incubated for 48 h but increase in a dose-dependent mannerwith respect to an increase in the concentration  inwhich complex 4 exhibits the lowest IC50 valueand exhibits the highest degree of SSB in DNA. 50 value after 48 h, the following trend in activity was observed: 4 > 7 > 2, which is the sametrendobserved in the degree of DNA damage and highlights a strong correlationbetween the two assays. The same trend is not observed for CDDP, whichexhibits low cytotoxicity after 48 h (IC50 = 76 ±3 μM); however, exhibits dose-dependent SSB similar to thatof complex 4. While other mechanisms are likely to beinvolved, the induction of SSB provides a possible cause of the apoptoticphenotype induced by these compounds. Induction of SSB is common forcisplatin; however, we cannot confirm the modes of action of our compoundswithout a full in-depth analysis, including double-strand breakage(DSB) and cross-linking assays. Complex 4 shows impressiveDNA interactions when compared to the low cellular uptake measuredby ICP-MS ruthenium ferrocenylβ-diketonato complexes (Staphylococcus aureus (S. aureus).21 We have screened complexes 1–24 for their antibacterial activityagainst ESKAPE pathogens , moderate to low activity againstGram negative K. pneumoniae and A. baumanni (E. coli or P. aeruginosa (Table S19). Although there are few distincttrends, generally, the most active complexes against S. aureus contain a Fc-acac ligand with neutral inductivearomatic ring systems , or increasing the number of halides inthe structure  can increase the activity by approximately2-fold. Similar trends are observed for the position of the F-substitutedcomplexes, where 17 (para) > 15 (meta) > 14 (ortho) > 16 (di-meta). Interestingly,decreasingelectronegativity of the halogen atoms F > Cl > Br > I causesa decreasein the activity of the complexes when the halogen atom is locatedat the para position, yet an increase in activityof the complexes when the halogen atom is located at the meta position. The opposite observation is true for electron-donatingsubstituents  and suggests that the inductive effectsaround the aromatic ring may be responsible to some degree in impartingbacterial inhibition properties to the complexes. Complexes that wereclassified as active underwent HIT confirmation to determine theirminimum inhibitory concentration , and complexes 2 and 9 are classified as active with MIC values of 16 μg/mL.All complexes were initially screened at 32 μg/mL and exhibitsignificantly high activity toward Gram-positive baumanni 7A and no1–24, complexes 2 and 9 were also the only compounds found to be activeagainst the C. neoformans strain, withinhibition concentrations of 116 and 120%, respectively , yet they were all inactive with MIC values of >32 μg/mL.The complexes have varying toxicities toward normal kidney cells ; however, hemolysis (Hm) results wereextremely positive, and all complexes exhibited no potency towardhuman blood at the maximum tested concentration of 32 μg/mL,which is important for the distribution of these complexes in thebloodstream.When addressing the fungal growth inhibition after incubation withcomplexes ectively 7B.Complep-cymeneRu(II) complexes, [(p-cym)RuCl(Fc-acac)], containingfunctionalized ferrocenylβ-diketonate ligands (Fc-acac), are reported, including sc-XRDdetermination for 21 of the complexes. The complexes have been screenedagainst MIA PaCa-2, HCT116 p53+/+, andARPE-19 cell lines. The complexes are generally more active towardMIA PaCa-2 than HCT116 p53+/+ and exhibitno cytotoxicity against the normal cell line (IC50 >100μM). This is contrary to the clinical platinum drugs CCDP andOXA, which remain cytotoxic; IC50 values of 6 ± 1μM and 6 ± 3 μM, respectively. Complex 4 (R = 2-furan) exhibits the highest cytotoxicity of this library(IC50 = 8 ± 2 μM) with a selectivity index (SI)of 12.5 against MIA PaCa-2.A library of 24 p-cymene and free Cp. This process is faster in the presence of waterbut slowed when 100 mM NaCl is added. Shortened-time exposure MTTand ICP-MS were used to study the uptake of the compounds into MIAPaCa-2 after 48 h. The highest uptake is not observed for the mostactive complexes and could be due to a lack of compound stability.UV–vis and NMR studies highlightthe complexes’ changeover 96 h, and while UV–vis data show changes to the Ru–Clbond, the NMR studies show decomposition to free + redox couple between 0.53 and 0.63 V (againstSCE), indicating that the formation of ROS is a reasonable mode ofaction. A correlation between the redox potential and cytotoxicityis not observed pointing out that further studies are necessary toassess the relevance of ROS to the overall toxicity. Complexes werealso tested under severely hypoxic (0.1% O2) conditionsagainst MIA PaCa-2; however, like CDDP, these complexes decrease inactivity and this could be due to inaccessible reduction potentials.Complexes 2, 4, and 7 werefurther tested for their ability to induce single-strand breakage(SSB) of DNA within MIA PaCa-2 cells with complex 4 exhibitingthe highest degree of damage, which is dose-dependent with respectto the concentration. The work highlights that complex 4 exhibits an impressive amount of DNA damage despite the lower concentrationof intracellular metal which was observed by ICP-MS. Further modificationsto this complex to improve cell uptake could therefore lead to significantlyenhanced cytotoxicity.Cyclic voltammetry studies are conducted revealing a reversibleFc*/Fc*S. aureus (83–95%),but no or low activity against Gram-negative strains. While the complexesshowed varying degrees of cytotoxicity toward HEK-293 cells, theyare all non-toxic towards human blood (HC10 > 32 μg/mL),which is important for the distribution of these complexes in thebloodstream.Finally, the growth inhibition of bacterialand fungal strains,human embryonic kidney (HEK-293) and hemolysis assays were conducted.The complexes have increased activity toward Gram-positive strains,for example, Supporting Information. Ligand L6 (±0.54%) and complexes 8 (±0.59%), 16 (±0.60%), 18 (±0.79), and 19 (±0.43) have elemental analysis values slightly higherthan expected, and although these results are outside the range viewedas establishing analytical purity, they are provided to illustratethe best values obtained to date. To support the results, we haveprovided high-resolution mass spectrometry data, which are withinrange, and single-crystal X-ray diffraction analysis for complexes 16, 18, and 19 to prove that productswere achieved successfully.The general methods, instrumentation,synthesis/characterizationof the ligands, X-ray crystallography, and biological assays can befound in the p-cymRuCl2]2 (1 equiv). The mixture was stirredat room temperature overnight. The solvent was removed in vacuo andpurified by column chromatography using 3:2 v/v petrol/ethyl acetate to yield orange solids.14A functionalizedferrocenyl ligand (2 equiv) was dissolved in dichloromethane (20 mL)followed by addition of triethylamine (2 equiv) and  calculated for C24H27ClFeO2Ru: 540.009. Found: 505.042 [MH+]-Cl.Yield: 0.14 g, 68%. 1H NMR 2CO, δ); 7.84  = 7.3 Hz, ortho ArC–H), 7.33  = 7.3 Hz, para ArC–H), 7.28  = 7.3 Hz, ortho ArC–H), 6.04 , 5.55  = 6.4 Hz, p-cymene ArC–H), 5.24  = 6.0 Hz, 4J(1H–1H) = 1.8 Hz, p-cymene ArC–H), 4.83  = 1.2 Hz,−CC4H4), 4.73 = 1.2 Hz, −CC4H4), 4.32  = 2.2, 1.4 Hz, −CC4H4), 4.28  = 2.3, 1.4 Hz, −CC4H4), 4.11 , 2.91  = 6.9Hz, p-cymene −CH(CH3)2), 2.16 , 1.34  = 7.3 Hz, p-cymene −CH(CH3)2). 13C{1H} NMR 2CO, δ); 186.8 (Q C–O),178.4 (Q C–O), 140.5 (Q Ar–C), 131.2 (ortho Ar–CH), 128.9 (meta Ar–CH), 127.9 (para Ar–CH), 99.4 (Q p-cymene −CCH(CH3)2), 97.8 (Q p-cymene −C(CH3)), 93.4 (methine−COCHCO−), 84.6 (p-cymene Ar–CH), 84.5 (p-cymene Ar–CH), 82.1 (Q Cp −CC4H4), 80.0 (p-cymene Ar–CH), 80.0 (p-cymene Ar–CH), 71.7 (Cp −CC4H4), 71.6 (Cp −CC4H4), 70.9 (Cp −C5H5), 69.9 (Cp −CC4H4), 68.7 (Cp −CC4H4), 31.7 (p-cymene −CH(CH3)2), 22.7 (p-cymene −CH(CH3)2), 22.6 (p-cymene −CH(CH3)2), 17.9 (p-cymene −C(CH3)). Analysiscalculated for C29H29ClFeO2Ru: C57.87, H 4.86, Cl 5.89%. Found: C 57.70, H 5.20, Cl 5.75%. HR-MS [ES+] calculated for C29H29ClFeO2Ru: 602.025. Found: 567.058 [MH+]-Cl.Yield: 0.21 g, 89%. 1H NMR2CO, δ); 8.54  = 7.8 Hz, NpC2–H), 7.82 = 8.0 Hz, NpC3–H), 7.78 = 7.1 Hz, 4J(1H–1H) = 2.1 Hz, NpC3–H), 7.45  = 7.1 Hz, NpC9–H), 7.37 , 5.72 ,5.57  = 5.7 Hz, p-cymene ArC–H), 5.53  = 5.9 Hz, p-cymeneArC–H), 5.25  = 4.9 Hz, p-cymene ArC–H), 4.83  = 0.7 Hz, Cp −CC4H4), 4.62  = 0.9 Hz, Cp −CC4H4), 4.33 , 4.27 , 4.14 , 2.86  = 6.9Hz, p-cymene −CH(CH3)2), 2.09 ), 1.30  = 6.7 Hz, p-cymene −CH(CH3)2). 13C{1H} NMR 2CO, δ); 186.9 (Q C–O),176.0 (Q C–O), 156.4 (Q Np–C1), 140.5 (Q Np–C10), 134.9(Q Np–C5), 132.0 (Np–C2H), 130.2(Np–C3H), 128.6 (Np–C4H), 128.4(Np–C9H), 126.8 (Np–C6H), 125.7(Np–C8H), 125.6 (Np–C7H), 99.72), 98.3 (methine −COCHCO−), 97.7 ), 84.4 (p-cymene Ar–CH), 84.2 (p-cymene Ar–CH), 81.5 (Q Cp −CC4H4), 80.1 (p-cymene Ar–CH), 80.1 (p-cymene Ar–CH), 71.9 (Cp −CC4H4), 71.9 (Cp −CC4H4), 71.0 (Cp −C5H5), 69.9 (Cp −CC4H4), 68.8 (Cp −CC4H4), 31.6 (p-cymene −CCH(CH3)2), 22.7 (p-cymene −CCH(CH3)2), 22.6 (p-cymene −CCH(CH3)2), 17.8 (p-cymene −C(CH3)). Analysis calculated for C33H31ClFeO2Ru: C 60.79, H 4.79, Cl 5.44%. Found:C 60.70, H 4.90, Cl 5.20%. HR-MS [ES+] calculated for C33H31ClFeO2Ru: 652.041. Found: 617.074[MH+]-Cl.Yield: 0.21 g, 82%. 1H NMR 2CO, δ); 7.53  = 0.9 Hz, Furan −C(O)C3H3), 6.96  = 3.4 Hz, Furan −C(O)C3H3), 6.44 = 3.7 Hz, 4J(1H–1H) = 1.6 Hz, Furan −C(O)C3H3), 5.92 , 5.53  = 6.3 Hz, p-cymene ArC–H), 5.20  = 5.7 Hz, p-cymene ArC–H), 4.79  = 1.2 Hz, Cp −CC4H4), 4.60  = 1.2 Hz, Cp −CC4H4), 4.32  = 2.5, 1.2 Hz, Cp−CC4H4), 4.28 = 2.5 Hz, 4J(1H–1H) = 1.2 Hz, Cp −CC4H4), 4.11 , 2.88  = 6.9 Hz, p-cymene−CH(CH3)2, H8), 2.14 ), 1.33  = 6.9 Hz, p-cymene −CH(CH3)2). 13C{1H} NMR 2CO, δ); 186.6 (Q C–O),168.6 (Q C–O), 163.6 (Q Furan −C(O)C3H3), 145.0(Furan −C(O)C3H3), 113.3 (Furan −C(O)C3H3), 112.9 (Furan −C(O)C3H3), 99.2(Q p-cymene −CCH(CH3)2), 97.9 ), 92.3 (methine −COCHCO−), 84.8 (p-cymene Ar–CH), 84.5 (p-cymene Ar–CH), 81.9 (Q Cp −CC4H4), 79.9 (p-cymene Ar–CH7), 79.8 (p-cymene Ar–CH), 71.7 (Cp −CC4H4), 71.7 (Cp −CC4H4), 70.9 (Cp −C5H5), 69.9 (Cp −CC4H4), 68.6 (Cp −CC4H4), 31.7 (p-cymene −CCH(CH3)2), 22.7 (p-cymene −CCH(CH3)2), 22.6 (p-cymene −CCH(CH3)2), 17.7 (p-cymene −C(CH3)). Analysis calculated for C27H27ClFeO3Ru: C 54.79, H 4.60, Cl 5.99%. Found:C 55.05, H 4.60 Cl 5.99%. HR-MS [ES+] calculated for C27H27ClFeO3Ru: 592.004. Found: 557.036[MH+]-Cl.Yield: 0.20 g, 86%. 1H NMR 2CO, δ); 8.19 C2H2), 7.60  = 1.6 Hz, Furan −CH(O)C2H2), 6.90 = 1.2 Hz, Furan −CH(O)C2H2), 5.97 , 5.68  = 6.1 Hz, p-cymene ArC–H), 5.35  = 5.3 Hz, p-cymene ArC–H), 4.96  = 1.2 Hz, −CC4H4), 4.84  = 1.2 Hz, −CC4H4), 4.44 , 4.40 , 4.25 , 3.04  = 6.9 Hz, p-cymene−CCH(CH3)2), 2.29), 1.49  = 6.9 Hz, 4J(1H–1H) = 0.9 Hz, p-cymene −CCH(CH3)2). 13C{1H} NMR 2CO, δ); 186.0 (Q C–O),173.6 (Q C–O), 145.0 (Furan −CCH(O)C2H2), 144.4(Furan −CCH(O)C2H2), 128.8 (Q Furan −CCH(O)C2H2), 109.8 (Furan −CCH(O)C2H2), 99.2(Q p-cymene −CCH(CH3)2), 97.8 (Q p-cymene −C(CH3)), 94.0 (methine −COCHCO−), 84.7 (p-cymene Ar–CH), 84.5 (p-cymene Ar–CH), 82.0 (Q Cp −CC4H4), 79.9 (p-cymene Ar–CH), 79.8 (p-cymene Ar–CH), 71.5 (Cp −CC4H4), 71.5 (Cp −CC4H4), 70.9 (Cp −C5H5), 69.8 (Cp −CC4H4), 68.6 (Cp −CC4H4), 31.7 (p-cymene −CCH(CH3)2), 22.7 (p-cymene −CCH(CH3)2), 22.6 (p-cymene −CCH(CH3)2), 17.7 (p-cymene −C(CH3)). Analysis calculated for C27H27ClFeO3Ru: C 54.79, H 4.60, Cl 5.99%. Found:C 54.72, H 4.55, Cl 6.01%. HR-MS [ES+] calculated for C27H27ClFeO3Ru: 592.004. Found: 557.043[MH+]-Cl.Yield: 0.19 g, 81%. 1H NMR 2CO, δ); 5.86  = 5.2 Hz, methine −COCHCO−),5.57  = 6.2 Hz, p-cymene ArC–H), 5.56 , 5.22  = 5.6 Hz, p-cymeneArC–H), 4.80 , 4.62 , 4.40 , 4.35 , 4.11 , 2.71  = 5.9Hz, p-cymene −CCH(CH3)2), 2.09 ), 1.30  = 5.9 Hz, p-cymene −CCH(CH3)2). 13C{1H} NMR 2CO, δ); 190.1 (Q C–O),172.8  = 22.1 Hz), 112.2 = 246.3 Hz), 99.5 (Q p-cymene −CCH(CH3)2), 98.2 (Q p-cymene −C(CH3)), 92.6 (methine −COCHCO−), 84.9 (p-cymene Ar–CH), 84.2 (p-cymene Ar–CH), 80.5 (Q Cp −CC4H4), 79.9 (p-cymene Ar–CH), 79.5 (p-cymene Ar–CH), 72.7 (Cp −CC4H4), 72.6 (Cp −CC4H4), 71.2 (Cp −C5H5), 70.1 (Cp −CC4H4), 69.1 (Cp −CC4H4), 31.7 (p-cymene −CCH(CH3)2), 22.6 (p-cymene −CCH(CH3)2), 22.5 (p-cymene −CCH(CH3)2), 17.7 (p-cymene −C(CH3)). Analysis calculated for C24H25ClF2FeO2Ru: C 50.06, H 4.38,Cl 6.16%. Found: C 50.30, H 4.40, Cl 6.30%. HR-MS [ES+]calculated for C24H25ClF2FeO2Ru: 575.990. Found: 541.023 [MH+]-Cl.Yield: 0.17 g, 77%. 1H NMR 2CO, δ); 5.63 , 5.61  = 5.5 Hz, p-cymene ArC–H), 5.30  = 5.5 Hz, p-cymene ArC–H), 5.27 , 4.83  = 1.4 Hz,−CC4H4), 4.68 = 1.4 Hz, −CC4H4), 4.46 , 4.41 , 4.13 , 2.83  = 6.9 Hz, p-cymene−CCH(CH3)2), 2.10), 1.17  = 7.3 Hz, p-cymene−CCH(CH3)2). 13C{1H} 2CO,δ); 218.9 (Q C–O), 191.8 (Q C–O), 99.5 (Q p-cymene −CCH(CH3)2), 98.3 (Q p-cymene −C(CH3)), 92.2 (methine−COCHCO−), 84.8 (p-cymene Ar–CH), 84.2 (p-cymene Ar–CH), 80.1 (Q Cp −CC4H4), 79.5 (p-cymene Ar–CH), 79.5 (p-cymene Ar–CH), 73.5 (Cp −CC4H4), 73.1 (Cp −CC4H4), 71.3 (Cp −C5H5), 70.9 (Cp −CC4H4), 67.5 (Cp −CC4H4), 31.8 (p-cymene −CCH(CH3)), 22.5(p-cymene −CCH(CH3)), 22.5 (p-cymene −CCH(CH3)2), 17.7 (p-cymene −C(CH3)). Analysiscalculated for C24H24ClF3FeO2Ru: C 48.54, H 4.07, Cl 5.97%. Found: C 48.90, H 4.10, Cl6.00%. HR-MS [ES+] calculated for C24H24ClF3FeO2Ru: 593.981. Found: 559.023 [MH+]-Cl.Yield: 0.20 g, 85%. 1H NMR 2CO, δ); 7.79 , 7.75, 7.29 , 6.15 , 5.68  = 4.9, 4J(1H–1H) = 1.5 Hz, p-cymeneArC–H), 5.36  = 4.9 Hz, 4J(1H–1H) = 1.5 Hz, p-cymene ArC–H), 4.96  = 1.2 Hz, −CC4H4), 4.84  = 1.2 Hz, −CC4H4), 4.44 , 4.40 , 4.24 , 3.04  = 6.9 Hz, p-cymene−CCH(CH3)2, H8), 2.42 , 2.29 ), 1.47  = 7.1 Hz, p-cymene−CCH(CH3)2). 13C{1H} NMR 2CO, δ); 186.6 (Q C–O), 178.6(Q C–O), 140.5 (Q Ar–C), 138.4 (Q Ar–C(CH3)), 131.8 (ortho Ar–CH), 128.8 (ortho Ar–CH), 128.5 (para Ar–CH), 125.1 (ortho Ar–CH), 99.4 2), 97.8 (Q p-cymene−C(CH3)), 93.4 (methine −COCHCO−), 84.6 (p-cymene Ar–CH), 84.5 (p-cymene Ar–CH), 82.1 (Q Cp −CC4H5), 80.0 (p-cymene Ar–CH), 80.0 (p-cymene Ar–CH), 71.6 (Cp −CC4H4), 71.6 (Cp −CC4H4), 70.9 (Cp −C5H5), 69.9 (Cp −CC4H4), 68.7 (Cp −CC4H4), 31.7 (p-cymene −CCH(CH3)2), 22.7 (p-cymene −CCH(CH3)2), 22.6 (p-cymene −CCH(CH3)2), 21.5 (meta Ar–C(CH3)), 17.8 (p-cymene −C(CH3)). Analysis calculated for C30H31ClFeO2Ru: C 58.50, H 5.07, Cl 5.76%. Found:C 57.91, H 5.06, Cl 5.82%. HR-MS [ES+] calculated for C30H31ClFeO2Ru: 616.041. Found: 581.072[MH+]-Cl.Yield: 0.23 g, 93%. 1H NMR 2CO, δ); 7.45 , 6.98,6.01 ,5.54  = 4.0 Hz, p-cymene ArC–H), 5.22  = 4.4 Hz, p-cymeneArC–H), 4.82 , 4.69 , 4.30 , 4.26 , 4.10 , 2.90  = 6.9Hz, p-cymene −CCH(CH3)2, H8), 2.21 ), 2.16 ), 1.34  = 6.9 Hz, p-cymene −CCH(CH3)2). 13C{1H} NMR 2CO, δ); 185.5(Q C–O), 178.0 (Q C–O), 139.6 (Q Ar–C), 137.4 (Q meta Ar–C), 131.7 (para Ar–CH), 124.9 (ortho Ar–CH), 124.5 (ortho Ar–CH), 98.5 (Q p-cymene −CCH(CH3)2), 96.9 (Q p-cymene −C(CH3)), 92.5 (methine −COCHCO−), 83.8 (p-cymene Ar–CH), 83.6 (p-cymene Ar–CH), 81.3 (Q Cp −CC4H4), 79.1 (p-cymene Ar–CH), 79.0 (p-cymene Ar–CH), 70.7 (Cp −CC4H4), 70.6 (Cp −CC4H4), 70.0 (Cp −C5H5), 69.0 (Cp −CC4H4), 67.8 (Cp −CC4H4), 30.8 (p-cymene −CCH(CH3)2), 22.7 (p-cymene −CCH(CH3)2), 22.6 (p-cymene −CCH(CH3)2), 20.6 (meta Ar–C(CH3)), 17.9 (p-cymene −C(CH3)). Analysis calculated for C31H33ClFeO2Ru: C 59.10, H 5.28, Cl 5.63%. Found: C 59.30, H5.30, Cl 5.50%. HR-MS [ES+] calculated for C31H33ClFeO2Ru: 630.056. Found: 595.090 [MH+]-Cl.Yield: 0.20 g, 80%; 1H NMR 2CO, δ); 7.74  = 8.3 Hz, ortho ArC–H), 7.10  = 7.8 Hz, meta ArC–H), 6.02 ,5.54  = 6.0 Hz, p-cymene ArC–H), 5.22  = 6.0 Hz, p-cymeneArC–H), 4.82  = 1.2 Hz, Cp −CC4H4), 4.71  = 1.2 Hz,Cp −CC4H4), 4.30, 4.27 , 4.11 , 2.90  = 6.9 Hz, p-cymene−CCH(CH3)2), 2.24), 2.16 ), 1.34  = 6.9 Hz, p-cymene −CCH(CH3)2). 13C{1H} 2CO, δ); 186.4 (Q C–O), 178.4 (Q C–O),141.4 (Q Ar–C), 137.7 (Q para Ar–C), 129.6 (ortho Ar–CH), 127.9 (meta Ar–CH), 99.4 (Q p-cymene −CCH(CH3)2), 97.8 (Q p-cymene −C(CH3)), 93.0 (methine −COCHCO−), 84.7 (p-cymene Ar–CH), 84.5 (p-cymene Ar–CH), 82.2 (Q Cp −CC4H4), 79.9 (p-cymene Ar–CH), 71.6 (Cp −CC4H4), 71.5 (Cp −CC4H4), 70.9 (Cp −C5H5), 69.9 (Cp −CC4H4), 68.6 (Cp −CC4H4), 31.7 (p-cymene −CCH(CH3)2), 22.7 (p-cymene −CCH(CH3)2), 22.6 (p-cymene −CCH(CH3)2), 21.4 (para Ar–C(CH3)), 17.8 (p-cymene −C(CH3)). Analysis calculated for C30H31ClFeO2Ru: C 58.50, H 5.07, Cl 5.76%. Found:C 58.60, H 5.10, Cl 5.80%. HR-MS [ES+] calculated for C30H31ClFeO2Ru: 616.041. Found: 581.072[MH+]-Cl.Yield: 0.18 g, 75%. 1H NMR 2CO, δ); 7.55 , 7.54 = 7.8 Hz, ortho ArC–H), 7.34  = 8.1 Hz, meta ArC–H), 7.06  = 7.3 Hz, 4J(1H–1H) = 1.7 Hz, para ArC–H), 6.17 ,5.72  = 2.4 Hz, p-cymene ArC–H), 5.39  = 2.4 Hz, p-cymeneArC–H), 4.99 , 4.89 , 4.47 = 0.9 Hz, Cp −CC4H4), 4.43  = 0.9 Hz, Cp CC4H4), 4.27 , 3.89 ), 3.07  = 6.7 Hz, p-cymene −CCH(CH3)2, H8), 2.33 ), 1.50  = 6.9 Hz, 4J(1H–1H) = 1.6 Hz, p-cymene −CCH(CH3)2). 13C{1H} 2CO, δ); 186.9 (Q C–O), 178.1 (Q C–O),160.6 (Q meta Ar–C(OCH3)), 142.0 (Q Ar–C), 129.9 (ortho Ar–CH), 120.1 (ortho Ar–CH), 116.9 (para Ar–CH), 113.3 (meta Ar–CH), 99.3 (Q p-cymene −CCH(CH3)2), 97.9 (Q p-cymene −C(CH2)), 93.5 (methine −COCHCO−), 84.7 (p-cymene Ar–CH), 84.7 (p-cymene Ar–CH), 82.1 (Q Cp −CC4H4), 79.9 (p-cymene Ar–CH), 79.9 (p-cymene Ar–CH), 71.7 (Cp −CC4H4), 71.7 (Cp −CC4H4), 70.9 (Cp −C5H5), 69.9 (Cp CC4H4), 68.8 (Cp −CC4H4), 55.6 (meta Ar–C(OCH3)), 31.7 (p-cymene −CCH(CH3)2), 22.8 (p-cymene −CCH(CH3)2), 22.6 (p-cymene −CCH(CH3)2), 17.8 (p-cymene −C(CH3)). Analysis calculated for C30H31ClFeO3Ru: C 57.02, H 4.94, Cl 5.61%. Found:C 57.09, H 4.90, Cl 5.53%. HR-MS [ES+] calculated for C30H31ClFeO3Ru: 632.036. Found: 597.068[MH+]-Cl.Yield: 0.20 g, 80%. 1H NMR 2CO, δ); 7.83  = 9.2 Hz, 4J(1H–1H) = 2.8 Hz, ortho ArC–H), 6.82  = 9.2 Hz, 4J(1H–1H) = 2.8 Hz, meta ArC–H), 6.01 , 5.53  = 6.0 Hz, 4J(1H–1H) = 0.9 Hz, p-cymene ArC–H), 5.21  = 6.4 Hz, p-cymene ArC–H), 4.82  = 1.2 Hz, Cp −CC4H4), 4.71  = 1.2 Hz, Cp −CC4H4), 4.92 , 4.25 , 4.10 , 3.73 ),2.91  = 6.9 Hz, p-cymene −CCH(CH3)2), 2.16 ), 1.34  = 7.3 Hz, p-cymene −CCH(CH3)2). 13C{1H} NMR 2CO, δ); 185.9(Q C–O), 178.0 (Q C–O), 162.7 (Q para Ar–C(OCH3)), 132.8 (Q Ar–C),129.7 (ortho Ar–CH),114.2 (meta Ar–CH),99.3 (Q p-cymene −CCH(CH3)2), 97.8 (Q p-cymene−C(CH3)), 92.6 (methine −COCHCO−), 84.6 (p-cymene Ar–CH), 84.5 (p-cymene Ar–CH), 82.4 (Q Cp −CC4H4), 79.9 (p-cymene Ar–CH), 79.9 (p-cymene Ar–CH), 71.4 (Cp −CC4H4), 71.4 (Cp −CC4H4), 70.9 (Cp −C5H5), 69.9 (Cp −CC4H4), 68.6 (Cp −CC4H4), 55.8 (para Ar–C(OCH3)), 31.7 (p-cymene −CCH(CH3)2), 22.7 (p-cymene −CCH(CH3)), 22.6(p-cymene −CCH(CH3)), 17.8 (p-cymene −C(CH3)). Analysis calculated for C30H31ClFeO3Ru: C 57.02, H 4.94, Cl 5.61%. Found: C 57.00, H5.00, Cl 5.50%. HR-MS [ES+] calculated for C30H31ClFeO3Ru: 632.036. Found: 597.066 [MH+]-Cl.Yield: 0.22 g, 89%. 1H NMR 2CO, δ); 7.82  = 8.9 Hz, ortho ArC–H),6.80  = 8.9 Hz, meta ArC–H), 6.00 ,5.53  = 4.8 Hz, 4J(1H–1H) = 1.2 Hz, p-cymene ArC–H), 5.21  = 5.2 Hz, p-cymene ArC–H), 4.82  = 1.2 Hz, Cp −CC4H4), 4.70  = 1.2 Hz,Cp −CC4H4), 4.29, 4.25 , 4.10 , 3.99  = 6.9 Hz, para ArC(OCH2CH3)), 2.90  = 6.9 Hz,−CCH(CH3)2), 2.16), 1.33  = 6.9 Hz, p-cymene−CCH(CH3)2) 1.26 = 6.9 Hz, para ArC(OCH2CH3)). 13C{1H} NMR 2CO, δ); 185.8 (Q C–O), 178.0 (Q C–O),162.1 (Q para Ar–C(OCH2CH3)), 132.6 (Q Ar–C), 129.7 (ortho Ar–CH), 114.7 (meta Ar–CH), 99.3 (Q p-cymene −CCH(CH3)2), 97.7 (Q p-cymene −C(CH3)), 92.5 (methine−COCHCO−), 84.6 (p-cymene Ar–CH), 84.5 (p-cymene Ar–CH6), 82.4 (QCp −CC4H4), 79.9(p-cymene Ar–CH), 79.9(p-cymene Ar–CH), 71.4(Cp −CC4H4), 71.4(Cp −CC4H4), 70.9(Cp −C5H5), 69.8(Cp −CC4H4), 68.6(Cp −CC4H4), 64.2(para ArC(OCH2CH3)), 31.7 (p-cymene −CCH(CH3)2), 22.8 (p-cymene −CCH(CH3)2), 22.6 (p-cymene −CCH(CH3)2), 17.9 (p-cymene −C(CH3)), 15.0 (para ArC(OCH2CH3). Analysis calculated for C31H33ClFeO3Ru: C 57.64, H 5.15, Cl 5.49%. Found:C 57.65, H 5.25, Cl 5.40%. HR-MS [ES+] calculated for C31H33ClFeO3Ru: 646.051. Found: 611.085[MH+]-Cl.Yield: 0.19 g, 75%. 1H NMR 2CO, δ); 7.87  = 7.7 Hz, 4J(1H–19F) = 1.2 Hz, ortho ArC–H), 7.49 , 7.28  = 7.6 Hz, meta ArC–H), 7.19  = 11.8 Hz, 4J(1H–19F) = 1.2 Hz, para ArC–H), 6.02 , 5.71  = 4.8Hz, p-cymene ArC–H),5.39  = 4.8 Hz, p-cymene ArC–H), 4.93  = 0.8 Hz, Cp −CC4H4), 4.75  = 0.9 Hz, Cp −CC4H4), 4.49 , 4.45, 4.27 , 3.04  = 6.9 Hz, p-cymene−CCH(CH3)2), 1.99), 1.48  = 6.9 Hz, p-cymene−CCH(CH3)2). 13C{1H} 2CO,δ); 187.1 (Q C–O), 174.8  = 3.6 Hz), 160.6  = 250.1 Hz), 132.3  = 8.8 Hz), 131.7 =3.1 Hz), 129.3  = 11.9 Hz),125.1  = 3.6 Hz), 116.9  = 23.9 Hz), 99.5 (Q p-cymene −CCH(CH3)2), 97.9  = 5.2 Hz), 97.8 (Q p-cymene−C(CH3)), 84.5 (p-cymene Ar–CH), 84.4 (p-cymene Ar–CH), 81.7 (Q Cp −CC4H4), 79.9 (p-cymene Ar–CH), 71.9 (Cp −CC4H4), 71.9 (Cp −CC4H4), 71.1 (Cp −CC5H5), 69.9 (Cp −CC4H4), 68.8 (Cp −CC4H4), 31.7 (pcymene −CCH(CH3)2), 22.7 (p-cymene −CCH(CH3)2), 22.6 (p-cymene −CCH(CH3)2), 17.9 (p-cymene −C(CH3)). Analysiscalculated for C29H28ClFFeO2Ru: C56.19, H 4.55, Cl 5.72%. Found: C 55.90, H 4.70, Cl 5.90%. HR-MS [ES+] calculated for C29H28ClFFeO2Ru: 620.016. Found: 585.049 [MH+]-Cl.Yield: 0.18 g, 72%. 1H NMR 2CO, δ); 7.70  = 7.8 Hz, ortho ArC–H),7.61  = 10.4 Hz, 4J(1H–1H) = 1.6, 0.9 Hz, ortho ArC–H), 7.36 , 7.14  = 8.3 Hz, 4J(1H–1H) = 2.3 Hz, meta ArC–H), 6.08 , 5.62  = 6.2 Hz, p-cymene ArC–H), 5.29  = 4.7 Hz, p-cymene ArC–H), 4.89  = 1.2 Hz, Cp −CC4H4), 4.81  = 1.2 Hz, Cp −CC4H4), 4.37 , 4.34 , 4.15 , 2.94  = 6.9Hz, p-cymene -CCH(CH3)2), 2.20 ), 1.38  = 7.1 Hz, p-cymene −CCH(CH3)2). 13C{1H} NMR 2CO, δ); 187.6 (Q C–O),179.1 (Q C–O), 164.6  = 243.9 Hz), 143.0  = 6.7 Hz), 130.8  = 8.3 Hz), 123.6  = 2.6 Hz), 117.7  = 21.3 Hz), 114.5  = 22.8 Hz), 99.5 (Q p-cymene −CCH(CH3)2), 97.9 (Q p-cymene −C(CH2)), 93.6 (methine−COCHCO−), 84.6 (p-cymene Ar–CH), 84.5 (p-cymene Ar–CH), 81.8 (Q Cp −CC4H5), 80.0 (p-cymene Ar–CH), 80.0 (p-cymene Ar–CH), 71.9 (Cp −CC4H4), 71.8 (Cp −CC4H4), 71.0 (Cp −C5H5), 70.0 (Cp −CC4H4), 68.9 (Cp −CC4H4), 31.7 (p-cymene −CCH(CH3)2), 22.7 (p-cymene CCH(CH3)2), 22.6 (p-cymene −CCH(CH3)2), 17.9 (p-cymene −C(CH3)). Analysiscalculated for C29H28ClFFeO2Ru::C 56.19, H 4.55, Cl 5.72%. Found: C 56.30, H 4.85, Cl 5.30%. HR-MS[ES+] calculated for C29H28ClFFeO2Ru: 620.016. Found: 585.048 [MH+]-Cl.Yield: 0.19 g, 78%. 1H NMR 2CO, δ); 7.45  = 6.9 Hz, ortho ArC–H), 6.99  = 8.9 Hz, 4J(1H–1H) = 2.1 Hz, para ArC–H), 6.05 ,5.60  = 6.0 Hz, p-cymene ArC–H), 5.28  = 5.0 Hz, p-cymeneArC–H), 4.87 , 4.83 , 4.36, 4.32 , 4.12 , 2.90  = 7.0 Hz, p-cymene−CCH(CH3)2), 2.17), 1.34  = 6.9 Hz, p-cymene −CCH(CH3)2). 13C{1H} NMR 2CO, δ); 188.4 (Q C–O), 174.6 (Q C–O),163.7  = 264.0 Hz, 3J(13C–19F) = 12.8 Hz), 144.3  = 8.3 Hz), 110.7  = 20.2, 6.2 Hz), 105.9  = 26.0 Hz), 99.6 2), 98.0 (Q p-cymene −C(CH3)), 93.7 (methine−COCHCO−), 84.6 (p-cymene Ar–CH), 84.5 (p-cymene Ar–CH), 81.6 (Q Cp −CC4H4), 80.0 (p-cymene Ar–CH), 72.1 (Cp −CC4H4), 72.0 (Cp −CC4H4), 71.0 (Cp −C5H5), 70.0 (Cp −CC4H4), 69.1 (Cp −CC4H4), 31.7 (p-cymene −CCH(CH3)2), 22.7 (p-cymene −CCH(CH3)2), 22.6 (p-cymene −CCH(CH3)2), 17.9 (p-cymene −C(CH3)). Analysiscalculated for C29H27ClF2FeO2Ru: C 54.60, H 4.27, Cl 5.56%. Found: C 55.20, H 4.40, Cl5.57%. HR-MS [ES+] calculated for C29H27ClF2FeO2Ru: 638.006. Found: 603.040 [MH+]-Cl.Yield: 0.19 g, 76%. 1H NMR 2CO, δ); 7.91  = 5.5, 3J(1H–19F) = 3.2 Hz, meta ArC–H), 7.04  = 8.7 Hz, meta ArC–H), 6.02 , 5.56  = 6.4 Hz, p-cymene ArC–H), 5.24  = 4.4 Hz, p-cymeneArC–H), 4.83  = 1.2 Hz, Cp −CC4H4), 4.73  = 1.2 Hz,Cp −CC4H4), 4.32 = 2.4, 1.1 Hz, Cp −CC4H4), 4.28  = 2.4, 1.1 Hz, Cp −CC4H4), 4.11 , 2.90  = 6.9Hz, p-cymene −CCH(CH3)2, H8), 2.16 ), 1.33  = 6.9 Hz, p-cymene −CCH(CH3)2); 13C{1H} NMR 2CO, δ); 187.0 (Q C–O), 177.0 (Q C–O),165.0  = 248.6 Hz), 136.9  = 3.1 Hz),130.3  =8.8 Hz), 115.6  = 21.8 Hz), 99.5 (Q p-cymene −CCH(CH3)2), 97.8 (Q p-cymene −C(CH3)), 93.2 (methine−COCHCO−), 84.6 (p-cymene Ar–CH), 84.5 (p-cymene Ar–CH), 82.0 (Q Cp −CC4H4), 80.0 (p-cymene Ar–CH), 71.7 (Cp −CC4H4), 71.7 (Cp −CC4H4), 70.9 (Cp −C5H5), 69.9 (Cp −CC4H4), 68.8 (Cp −CC4H4), 31.7 (p-cymene −CCH(CH3)2), 22.7 (p-cymene −CCH(CH3)2), 22.6 (p-cymene −CCH(CH3)2), 17.9 (p-cymene −C(CH3)). Analysiscalculated for C29H28ClFFeO2Ru: C56.19, H 4.55, Cl 5.72%. Found: C 56.20, H 4.95, Cl 5.95%. HR-MS [ES+] calculated for C29H28ClFFeO2Ru: 620.016. Found: 585.047 [MH+]-Cl.Yield: 0.12 g, 82%. 1H NMR 2CO, δ); 7.99  = 1.8 Hz, ortho ArC–H), 7.93  = 7.8 Hz, 4J(1H–1H) = 1.4 Hz, ortho ArC–H), 7.52  = 8.0 Hz, 4J(1H–1H) = 1.1 Hz, para ArC–H), 7.46  = 7.8 Hz, meta ArC–H), 6.20 , 5.73  = 4.8 Hz, 4J(1H–1H) = 1.4 Hz, p-cymene ArC-H), 5.42  = 5.0 Hz, p-cymene ArC–H), 5.01  = 1.3 Hz, Cp −CC4H4), 4.93  = 1.3 Hz,Cp −CC4H4), 4.49, 4.45 , 4.27 , 3.06  = 6.9 Hz, p-cymene−CCH(CH3)2), 2.32), 1.50  = 7.1 Hz, p-cymene−CCH(CH3)2); 13C{1H} NMR 2CO, δ); 187.7 (Q C–O), 176.3(Q C–O), 142.6 (meta Ar–CCl), 134.6 (Q Ar–C), 130.9 (ortho Ar–CH), 130.7 (ortho Ar–CH), 127.8 (para Ar–CH), 126.2 (meta Ar–CH), 99.5 (Q p-cymene −CCH(CH3)2), 97.6 (Q p-cymene −C(CH3)), 93.6 (methine−COCHCO−), 84.6 (p-cymene Ar–CH), 84.5 (p-cymene Ar–CH), 81.8 (Q Cp −CC4H4), 80.0 (p-cymene Ar–CH), 80.0 (p-cymene Ar–CH), 71.9 (Cp −CC4H4), 71.9 (Cp −CC4H4), 71.0 (Cp −C5H5), 70.0 (Cp −CC4H4), 68.9 (Cp −CC4H4), 31.7 (p-cymene −CCH(CH3)2), 22.7 (p-cymene −CCH(CH3)2), 22.6 (p-cymene −CCH(CH3)2), 17.9 (p-cymene −C(CH3)). Analysis calculated for C29H28Cl2FeO2Ru: C 54.74, H 4.44, Cl11.14%. Found: C 53.95, H 4.51, Cl 11.06%. HR-MS [ES+]calculated for C29H28Cl2FeO2Ru: 635.986. Found: 601.018 [MH+]-Cl.Yield: 0.23 g, 92%. 1H NMR 2CO, δ); 7.94  = 1.8 Hz, ortho ArC–H), 7.59  = 1.8 Hz, para ArC–H), 6.21 ,5.75  = 5.7 Hz, p-cymene ArC–H), 5.44  = 5.7 Hz, p-cymeneArC–H), 5.03  = 0.9 Hz, Cp −CC4H4), 4.98  = 1.1 Hz,Cp −CC4H4), 4.52, 4.47 , 4.27 , 3.05 2), 2.32 ), 1.49  = 7.1 Hz, p-cymene −CCH(CH3)2); 13C{1H} NMR 2CO, δ); 187.7 (Q C–O),17.5 (Q C–O), 143.0 (Q meta Ar–CCl), 134.6 (Q Ar–C), 129.4 (ortho Ar–CH), 125.5 (para Ar–CH), 98.7 (Q p-cymene −CCH(CH3)2), 97.0 (Q p-cymene −C(CH)3), 92.9 (methine−COCHCO−), 83.7 (p-cymene Ar–CH), 83.6 (p-cymene Ar–CH), 80.6 (Q Cp −CC4H4), 79.2 (p-cymene Ar–CH), 79.1 (p-cymene Ar–CH), 71.3 (Cp −CC4H4), 71.2 (Cp −CC4H4), 70.1 (Cp −C5H5), 69.2 (Cp −CC4H4), 68.2 (Cp −CC4H4), 30.9 (p-cymene −CCH(CH3)2), 21.8 (p-cymene −CCH(CH3)2), 21.7 (p-cymene −CCH(CH3)2), 17.0 (p-cymene −C(CH3)). Analysiscalculated for C29H27Cl3FeO2Ru·H2O: C 50.57, H 4.24, Cl 15.44%. Found: C 51.00,H 3.90, Cl 15.89%. HR-MS [ES+] calculated for C29H27Cl3FeO2Ru: 669.947. Found: 634.979[M+]-Cl.Yield: 0.16 g, 61%. 1H NMR 2CO, δ); 7.86  = 8.7 Hz, ortho ArC–H), 7.31  = 8.7 Hz, meta ArC–H), 6.03 ,5.56  = 6.0 Hz, p-cymene ArC–H), 5.24  = 4.6 Hz, p-cymeneArC–H), 4.84  = 1.4 Hz, Cp −CC4H4), 4.74  = 1.2 Hz,Cp −CC4H4), 4.33 = 2.3, 1.2 Hz, Cp −CC4H4), 4.29  = 2.3, 1.4 Hz, Cp −CC4H4), 4.11 , 2.90  = 6.9 Hz,−CCH(CH3)2), 2.16), 1.33  = 6.9 Hz, p-cymene−CCH(CH3)2); 13C{1H} NMR 2CO, δ); 187.3 (Q C–O), 176.8(Q C–O), 139.2 (Q Ar–C), 136.6 (Q para Ar–C), 129.6 (ortho Ar–CH), 129.0 (meta Ar–CH), 99.5 (Q p-cymene −CCH(CH3)2), 97.8 (Q p-cymene −C(CH3)), 93.4 (methine−COCHCO−), 84.6 (p-cymene Ar–CH), 84.5 (p-cymene Ar–CH), 81.9 (Q Cp −CC4H4), 80.0 (p-cymene Ar–CH), 71.9 (Cp −CC4H4), 71.8 (Cp −CC4H4), 71.0 (Cp −C5H5), 70.0 (Cp −CC4H4), 68.8 (Cp −CC4H4), 31.74 (p-cymene −CCH(CH3)2), 22.7 (p-cymene −CCH(CH3)2), 22.6 (p-cymene −CCH(CH3)2), 17.9 (p-cymene −C(CH3)). Analysiscalculated for C29H28Cl2FeO2Ru: C 54.74, H 4.44, Cl 11.14%. Found: C 54.90, H 4.50, Cl 11.10%.HR-MS [ES+] calculated for C29H28Cl2FeO2Ru: 635.986. Found: 601.016 [MH+]-Cl.Yield: 0.23 g, 91%. 1H NMR 2CO, δ); 7.99  = 1.7 Hz, ortho ArC–H), 7.81  = 7.8 Hz, 4J(1H–1H) = 1.1 Hz, ortho ArC–H), 7.51  = 7.8 Hz, 4J(1H–1H) = 0.9 Hz, para ArC–H), 7.24  = 7.8 Hz, meta ArC–H), 6.03 , 5.57  = 5.0 Hz, 4J(1H–1H) = 1.4 Hz, p-cymene ArC–H), 5.26  = 5.0 Hz, p-cymeneArC–H), 4.85  = 1.2 Hz,Cp −CC4H4), 4.77 = 1.2 Hz, Cp −CC4H4), 4.34 , 4.30 , 4.11 , 2.90  = 6.9 Hz, p-cymene−CCH(CH3)2), 2.16), 1.33  = 7.1 Hz, p-cymene−CCH(CH3)2); 13C{1H} 2CO,δ); 187.7 (Q C–O), 176.2 (Q C–O), 142.8 (Q meta Ar–C), 133.8 (ortho Ar–CH), 130.9 (ortho Ar–CH), 130.8 (meta Ar–CH), 126.6 (para Ar–CH), 122.8 (meta Ar–CBr), 99.5 (Q p-cymene −CCH(CH3)2), 97.9 (Q p-cymene−C(CH3)), 93.6 (methine −COCHCO−), 84.6 (p-cymene Ar–CH), 84.5 (p-cymene Ar–CH), 81.7 (Q Cp −CC4H4), 80.1 (p-cymene Ar–CH), 80.0 (p-cymene Ar–CH), 72.0 (Cp −CC4H4), 71.9 (Cp −CC4H4), 71.0 (Cp −C5H5), 70.0 (Cp −CC4H4), 68.9 (Cp −CC4H4), 31.7 (p-cymene −CCH(CH3)2), 22.7 (p-cymene −CCH(CH3)2), 22.6 (p-cymene −CCH(CH3)2), 17.9 (p-cymene −C(CH3)). Analysis calculated for C29H28BrClFeO2Ru: C 51.16, H 4.15%. Found: C 51.06,H 4.18%. HR-MS [ES+] calculated for C29H28BrClFeO2Ru: 679.935. Found: 646.967 [MH+]-Cl.Yield: 0.23 g, 84%. 1H NMR 2CO, δ); 7.78  = 8.7 Hz, ortho ArC–H), 7.46  = 8.7 Hz, meta ArC–H), 6.03 ,5.56  = 6.2 Hz, p-cymene ArC–H), 5.24  = 4.7 Hz, p-cymeneArC–H), 4.83  = 1.3 Hz, Cp −CC4H4), 7.47  = 1.3 Hz,Cp −CC4H4), 4.33, 4.29 , 4.11 , 2.90  = 6.9 Hz, p-cymene−CCH(CH3)2), 2.16), 1.33  = 6.9 Hz, p-cymene−CCH(CH3)2). 13C{1H} NMR 2CO, δ); 194.4 (Q C–O), 189.7(Q C–O), 139.7 (Q Ar–C), 132.0 (ortho Ar–CH), 129.8 (meta Ar–CH), 106.7 (para Ar–CBr), 99.5 (Q p-cymene −CCH(CH3)2), 97.8 (Q p-cymene −C(CH3)), 93.4 (methine−COCHCO), 84.6 (p-cymeneAr–CH), 84.5 (p-cymeneAr–CH), 81.9 (Q Cp −CC4H4), 80.0 (p-cymene Ar–CH), 80.0 (p-cymene Ar–CH), 71.9 (Cp −CC4H4), 71.8 (Cp −CC4H4), 71.0 (Cp −C5H5), 69.9 (Cp −CC4H48), 68.8 (Cp −CC4H4), 31.7 (p-cymene −CCH(CH3)2), 22.7 (p-cymene −CCH(CH3)2), 22.6 (p-cymene −CCH(CH3)2), 17.9 (p-cymene −C(CH3)). Analysiscalculated for C29H28BrClFeO2Ru:C 51.16, H 4.15%. Found: C 51.20, H 4.20%. HR-MS [ES+]calculated for C29H28BrClFeO2Ru:679.935. Found: 644.968 [M+]-Cl.Yield: 0.17 g, 64%. 1H NMR 2CO, δ); 8.20  = 1.6 Hz, ortho ArC–H), 7.83  = 8.0 Hz, 4J(1H–1H) = 1.2 Hz, ortho ArC–H), 7.71  = 7.8 Hz, 4J(1H–1H) = 0.7 Hz, para ArC–H), 7.10  = 7.8 Hz, meta ArC–H), 6.01 , 5.57  = 4.81, 4J(1H–1H) = 1.3 Hz, p-cymene ArC–H), 5.26  = 5.0 Hz, p-cymeneArC–H), 4.85  = 1.2 Hz, Cp −CC4H4), 4.76  = 1.2 Hz,Cp −CC4H4), 4.34, 4.30 , 4.11 , 2.90  = 6.9 Hz, p-cymene−CCH(CH3)2), 2.16), 1.34  = 7.1 Hz, p-cymene−CCH(CH3)2); 13C{1H} NMR 2CO, δ); 187.6 (Q C–O), 176.3(Q C–O), 142.7 (Q Ar–C), 139.9 (ortho Ar–CH), 136.9 (ortho Ar–CH), 131.0 (meta Ar–CH), 127.0 (para Ar–CH), 105.9 (ortho Ar–CCI), 99.5 (Q p-cymene −CCH(CH3)2), 97.8 (Q p-cymene −C(CH3)2), 93.5 (methine −COCHCO−),84.5 (p-cymene Ar–CH), 84.5 (p-cymene Ar–CH), 81.8 (Q −CC4H4), 80.1 (p-cymene Ar–CH), 80.0 (p-cymene Ar–CH), 71.9 (Cp −CC4H4), 71.9 (Cp −CC4H4), 71.0 (Cp −C5H5), 70.0 (Cp −CC4H4), 68.9 (Cp −CC4H4), 31.7 (p-cymene −CCH(CH3)2), 22.7 (p-cymene -CCH(CH3)2), 22.6 (p-cymene −CCH(CH3)2), 17.8 (p-cymene −C(CH3)). Analysis calculated for C29H28ClFeIO2Ru: C 47.86, H 3.88%. Found: C 47.89, H 3.72%.HR-MS [ES+] calculated for C29H28ClFeIO2Ru: 727.922. Found: 692.954 [M+]-Cl.Yield: 0.23 g, 80%; 1H NMR 2CO, δ); 7.66  = 12.8 Hz, ortho and meta ArC–H), 6.02 , 5.56 , 5.24 , 4.83 , 4.73 , 4.31  = 18.6 Hz,Cp −CC4H4), 4.11, 2.90  = 6.8 Hz, p-cymene −CCH(CH3)2), 2.15 ), 1.34  = 6.2 Hz, p-cymene −CCH(CH3)2); 13C{1H} 2CO, δ); 187.1 (Q C–O), 178.8 (Q C–O),140.2 (Q Ar–C), 138.2 (ortho Ar–CH), 129.8 (meta Ar–CH), 105.9 (para Ar–CI), 99.5 (Q p-cymene −CCH(CH3)2), 97.8 (Q p-cymene −C(CH3)), 93.3 (methine −COCHCO−), 84.6 (p-cymene Ar–CH), 84.5 (p-cymene Ar–CH), 81.9 (Q Cp −CC4H4), 80.0 (p-cymene Ar–CH), 80.0 (p-cymene Ar–CH), 71.9 (Cp −CC4H4), 71.8 (Cp −CC4H4), 71.0 (Cp −C5H5), 69.9 (Cp −CC4H4), 68.8 (Cp −CC4H4), 31.7 (p-cymene −CCH(CH3)2), 22.7 (p-cymene −CCH(CH3)2), 22.6 (p-cymene −CCH(CH3)2), 17.9 (p-cymene −C(CH3)). Analysis calculated for C29H28ClFeIO2Ru: C 47.86, H 3.88%. Found: C 48.00,H 3.90%. HR-MS [ES+] calculated for C29H28ClFeIO2Ru: 727.922. Found: 692.955 [M+]-Cl.Yield: 0.29 g, 79%.


In the original publication , there wn = 176) as published. During figure editing, the labels for premenopausal and postmenopausal women were accidentally switched. The first group should be postmenopausal and the second group should be premenopausal.In the original publication , there wAn error in the mean values and SD of free 25(OH)D was also noticed. Due to mistakenly placed decimal points, the values and SD presented in the graph were higher . Additionally, there was a mistake in the caption of Figure 3. The figure presents differences between total, free, and bioavailable 25(OH)D concentrations. However, in the published version, only total 25(OH)D concentrations are mentioned. For better clarity, the caption has been corrected to include the missing information.The corrected n = 176). Mean values and SD of free 25(OH)D were presented with wrong decimal point. The corrected In the original publication , there wThe authors apologize for any inconvenience caused and state that the scientific conclusions are unaffected. This correction was approved by the Academic Editor. The original publication has also been updated.


Biol. Open (2017) 6, 1123-1129 (doi:10.1242/bio.025767).There are potential issues in Figs 2 and 5 in It appears that there may be duplication of the GAPDH blots in Figs 2C and 5A and the β-actin blots in Figs 2D and Fig 5C.We have made multiple attempts to contact all authors to request original data for the affected figures but have not received a response. Therefore, the journal is publishing this note to alert readers to our concerns.


After having been in contact with the authors, they accepted the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused.Owing to the fact that some of the data in the above article were already under consideration for publication prior to its submission to


After having consulted the authors in this regard, they agreed with the decision to retract this paper. The Editor deeply regrets any inconvenience that has been caused to the readership of the Journal.After having conducted an independent investigation in the Editorial Office, the Editor of


In the original publication , there wThe authors state that the scientific conclusions are unaffected. This correction was approved by the Academic Editor. The original publication has also been updated with the correct


The authors wish to make the following changes to their paper . In the The authors apologize for any inconvenience caused and state that the scientific conclusions are unaffected. This correction was approved by the academic editor. The original publication has also been updated.


Non-coding RNA are a class of RNA that lack the potential to encode proteins. CircRNAs, generated by a post-splicing mechanism, are a newly discovered type of non-coding RNA with multi-functional covalent loop structures. CircRNAs may play an important role in the occurrence and progression of tumors. Research has shown that circRNAs are aberrantly expressed in various types of human cancers, including leukemia. In this review, we summarize the expression and function of circRNAs and their impact on different types of leukemia. We also illustrate the function of circRNAs on immune modulation and chemoresistance in leukemia and their impact on its diagnosis and prognosis. Herein, we provide an understanding of recent advances in research that highlight the importance of circRNAs in proliferation, apoptosis, migration, and autophagy in different types of leukemia. Furthermore, circRNAs make an indispensable difference in the modulation of the immunity and chemoresistance of leukemia. Increasing evidence suggests that circRNAs may play a vital role in the diagnostic and prognostic markers of leukemia because of their prominent properties. More detailed preclinical studies on circRNAs are needed to explore effective ways in which they can serve as biomarkers for the diagnosis and prognosis of leukemia in vivo. Leukemia is a type of blood cancer derived from hematopoietic stem and progenitor cells . These cCircular RNAs (circRNAs) are an abundant class of endogenous noncoding RNAs (ncRNAs) that are characterized by covalently closed loop structures with no exposed 3′  and 5′  ends . This stThe current research on circRNAs in leukemia is not comprehensive. Here, we briefly review the impact of the expression and function of circRNAs on different human leukemias, focusing on the role of circRNAs in leukemia immunomodulation and chemoresistance, as well as the potential of circRNAs in leukemia diagnosis and prognosis. This review help researchers to quickly understand the recent research progress of circRNAs in human leukemia and provide valuable information for future research directions.CircRNAs are non-coding RNA with multiple functions that have a covalent-loop structure. Leukemia is a blood cancer derived from hematopoietic stem and progenitor cells. The current research on circRNAs in leukemia is not comprehensive. Therefore, we briefly reviewed the impact of the expression and function of circRNAs on different human leukemias, focusing on the role of circRNAs in leukemia immunomodulation and chemoresistance. We also focused on the potential of circRNAs in the diagnosis and prognosis of the disease as well as some issues faced by circRNAs in human leukemia. The preclinical studies of circRNAs need to be further developed to explore their use as diagnostic and prognostic biomarkers in leukemia in vivo. In summary, this review is meant to help researchers quickly understand the recent research progress concerning the role of circRNAs in human leukemia and to provide valuable information for future research directions.To ensure an inclusive and unbiased analysis of the literature and to accomplish the review objectives, we searched the following literature databases: PubMed, Google Scholar and Web of Science. The search terms included: circRNA, leukemia, chemoresistance, immune modulation, and biomarker. It is worth noting that the keywords used and their variants and related words can be sorted, combined, and then searched.1. The terms searched for circRNA were: circRNA, circular RNA, noncoding RNA, circular intronic RNA, exon-intron circRNA, epigenetic, epigenetic regulation.2. The terms searched for leukemia were: leukemia, acute myeloid leukemia, acute myeloid leukemia, chronic myeloid leukemia, chronic lymphocytic leukemia, AML, ALL, CML, CLL.3. The terms searched for circRNA and leukemia were: chemoresistance, immune modulation, biomarker.This article is based on published literature. The aspects of the inclusion criteria are the retrieval keywords, information not covered by previous literature, and most importantly, the use of a clear and credible source.Acute myelogenous leukemia (AML) is a highly aggressive malignancy of hematopoietic stem cells. A series of studies have shown that circRNAs are aberrantly expressed in AML . Sun et in vitro and in vivo (Acute lymphoblastic leukemia (ALL) is a common type of malignancy that occurs in children. Growing evidence indicates that circRNAs may act as an oncogene, playing an important role in the development of ALL. It was reported that circPVT1 was significantly highly expressed in ALL patients, and knocking out circPVT1 could provoke apoptosis and suppresses the proliferation of ALL cells . Similar in vivo . TherefoChronic myelogenous leukemia (CML) is a myeloproliferative disease that originates primarily from hematopoietic stem cells. Studies have shown that a variety of circRNAs are aberrantly expressed in CML. via the circ_0132266/miR-337-3p/PML axis, demonstrating that circ_0132266 was crucial for the malignant proliferation of CLL (Wu 2019). Circ-RPL15, a circRNA aberrantly expressed in CLL patients, was found to regulate the RAS/RAF1/MEK/ERK signaling pathway by binding to miR-146b-3p, affecting CLL progression  is a clonal disease of mature B cells. Existing research has found that some circRNAs are expressed abnormally in CLL. gression . Xia et t of CLL . A mitoct of CLL .etc., have obvious curative effects in the early stages of administration. Over time, however, the efficacy of these drugs declines significantly, and leukemia patients may develop resistance to these drugs. Growing evidence has suggested that circRNAs significantly impact the chemoresistance of leukemia patients (via the miR-345-5p/FZD5 axis, indicating that circNPM1 was a potential marker in AML drug resistance therapy. circPAN3 was found to be abnormally highly expressed in doxorubicin-resistant AML cells, indicating that circPAN3 may promote AML resistance to doxorubicin by regulating cellular autophagy and affecting apoptosis-related proteins expression through the AMPK/mTOR signaling pathway (As with many other cancers, drug resistance in leukemia patients is a difficult issue to address. Commonly used drugs for the treatment of leukemia, such as rituximab, chlorambucil, bendamustine, patients . Cao et patients . Ding et pathway . In addi pathway . Ping et pathway . The aboImmune regulation means that the various immune cells and immune molecules of the body maintain their own physiologically dynamic balance and relative stability by promoting and restricting each other. Depending on the type of immune cells, the immune system can induce a series of responses to fight viruses, bacteria, and tumors. It is worth noting that circRNAs can be involved in some regulatory responses of the immune system. Recently, a number of circRNAs have been found to be aberrantly expressed in leukemia. A growing body of evidence points the use of circRNAs as effective biomarkers for the diagnosis and prognosis of leukemia due to their unique properties . For exaAt present, chemotherapy remains one of the most effective methods of treatment for leukemia. With the rapid development of technology, circRNAs have opened up a new research field as a novel type of non-coding RNA. Increasing evidence suggests that circRNAs can broadly regulate human physiological and pathological processes, especially in leukemia. In this review, we provided an overview of the latest research advances in circRNAs and highlighted the role they play in leukemia.in vitro experiments such as cells and tissues, and has not been applied to the clinical setting. Therefore, we need to increase our preclinical investment to explore effective methods of applying circRNAs as biomarkers for the diagnosis and prognosis in leukemia in vivo. First, more in vitro experiments should be conducted to screen for efficient and expected circRNAs. Second, a robust circRNA database should be established, especially those with tissue specificity. Third, novel tools and methods should be developed to improve the specificity of circRNA detection. In conclusion, circRNAs are a class of regulatory factors that can play an important role in leukemia, and they can regulate the occurrence and development of leukemia. Therefore, it is necessary to strengthen the research on circRNAs in the future so that the results can be transferred from in vitro research to in vivo research. These applications will better serve those affected by leukemia and will allow for the development of precision medicine in the near future.Increasing amounts of research have shown that circRNAs are aberrantly expressed in leukemia . CircRNA


In


The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused.The Editorial Office have conducted an independent assessment of these data, and can confirm the veracity of the concerns that were raised by the reader; therefore, the Editor of


Following publication, concerns were raised regarding the contributions of the authors of the article.Our investigation, conducted in accordance with Frontiers policies, confirmed a serious breach of our authorship policies and of publication ethics; the article is therefore retracted.The authors do not agree to this retraction.This retraction was approved by the Chief Editors of Frontiers in Bioengineering and Biotechnology and the Chief Executive Editor of Frontiers.


Correction to: Pediatric Radiology (2023)https://doi.org/10.1007/s00247-023-05618-5The initial online version states that all authors participated in the roundtable discussion.Correction:Only the following authors participated in the roundtable discussion.Chair: A.C.O.Panel/speakers: A.M.J., K.M., I.M., M.R.The original article has been corrected.


There was an unclear passage in the original publication . The valSection 3, Results”:A correction has been made to “τ = 4.02 × 10−7 J/m. Furthermore, for better display of the validity of the measurement results, Cθ versus one divided by the radius of the spheres was plotted too . The solid red line corresponds to the previously determined τ. The two additional dotted lines correspond to 2 τ and 1/2 τ. Thus, more than 90% of the data points are located in the funnel that spans between −8.04 × 10−7 J/m < τ < −2.01 × 10−7 J/m.”“From this fit, we determined an absolute value for the apparent line tension, In the original publication, Ref. [22] was not cited correctly, it should change as follows:Phys. Rev. Lett.2019, 123, 94501New Ref. 22: Zhao, B.; Luo, S.; Bonaccurso, E.; Auernhammer, G.K.; Deng, X.; Li, Z.; Chen, L. Resolving the Apparent Line Tension of Sessile Droplets and Understanding its Sign Change at a Critical Wetting Angle. The authors apologize for any inconvenience caused and state that the scientific conclusions are unaffected. This correction was approved by the Academic Editor. The original publication has also been updated.


Following the publication of this article , concernLanes 2–4 of the Fig 5C Atg5 panel and the Fig 8C Akt panel.Lanes 2–5 of the Fig 3A p62 panel of this study  and the The Fig 3D Tubulin panel of this study  and the The Fig5C Akt panel of this study  and laneLanes 1–2 of the Fig 5C Akt panel of this study .The Fig 7C Akt panel of this study  and the The Fig 8C p62 panel of this study  and laneLanes 1–4 of the Fig S3A AMPK panel of this study .Lanes 2–5 of the Fig S3A AMPK panel of this study  and the The corresponding author commented that some western blot images were misused in this article  and requPLOS ONE Editors retract this article.In light of the concerns affecting multiple figure panels that question the integrity of these data, the CW agreed with the retraction. FG, YD, YZhang, YZhou, and ML either did not respond directly or could not be reached.


In “Psychiatric Treatment Conducted via Telemedicine Versus In-Person Modality in Posttraumatic Stress Disorder, Mood Disorders, and Anxiety Disorders: Systematic Review and Meta-Analysis” , the authors noted one error.In The correction will appear in the online version of the paper on the JMIR Publications website on September 18, 2023 together with the publication of this correction notice. Because this was made after submission to PubMed, PubMed Central, and other full-text repositories, the corrected article has also been resubmitted to those repositories.


In the original publication , there wThe authors state that the scientific conclusions are unaffected. This correction was approved by the Academic Editor. The original publication has also been updadated.


RSC Advances is publishing this expression of concern in order to alert our readers that we are presently unsure of the reliability of the data reported in Fig. 2 of the article. Fig. 2a and b are identical. The authors have requested Fig. 2b be removed from the article but are unable to provide a replacement for Fig. 2b. An independent expert has stated it would not be appropriate to remove Fig. 2b completely and requested the authors reproduce their results.An expression of concern will continue to be associated with the article until we receive conclusive evidence regarding the reliability of the reported data.Laura Fisher9th March 2023RSC AdvancesExecutive editor,


Cell Discovery (2021) 7:59Correction to: 10.1038/s41421-021-00285-y published online 03 August 2021The authors apologize for an error in Fig.


This paper  presentsHowever, the topic of cybersecurity and privacy will never be outdated since the evolution of COVID-19. The authors must work a lot more to identify the knowledge gap in the existing literature first and then propose novel viewpoints to bridge the gaps. Before drawing a conclusion, the authors must add a discussion on how their findings compare to other studies (references) that were published very recently.Appropriate references to related work are not covered sufficiently in the list, especially for the contact tracing section. A systematic review of the global deployment status of contact tracing apps is recommended, as in .In addition to the majority of qualitative descriptions, quantitative statistics are suggested to complement and support the statements in the manuscript.After the first round of review, the reviewer appreciates the revision effort the authors have made in improving the manuscript.However, the authors may need to redefine the contribution and the title in a more specific and unique manner.The current title looks quite broad and not new, as a number of similar articles have been disseminated on the web eg, ,4)..4]).The authors might consider reducing the overlap with published work as illustrated above.


In the original published version of this article, the typesetters have used the outdated version, the authors reviewed the proof and approved it before publication. An outdated version of the paper was published. We will publish a final version that the authors and editors approved. The correct version of the manuscript will replace the outdated version. The authors apologize for the errors. Both the HTML and PDF versions of the article have been updated to correct the errors.The authors declare no conflict of interest.


JCI Insight. 2020;5(9):e132747. https://doi.org/10.1172/jci.insight.132747Original citation: JCI Insight. 2023;8(6):e169756. https://doi.org/10.1172/jci.insight.169756Citation for this corrigendum: 2+ chelator, but instead reduces Fe2+ via conversion to Fe3+. As MFG mediates reduction of Fe2+ and suppresses ferroptosis, the overall conclusions are not affected. For clarity, the authors have removed references to MFG-mediated chelation throughout, updated the Graphical Abstract, and renumbered the reference list to refer to Hirayama et al. .The authors recently became aware that the Mito-FerroGreen (MFG) used in this study is not an Fea et al.  when firThe authors regret the errors.


In the original publication . In FiguThe authors apologize for any inconvenience caused and state that the scientific conclusions are unaffected. This correction was approved by the Academic Editor. The original publication has also been updated.


After having been in contact with the authors, they accepted the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused.Owing to the large number of overlapping data panels identified in comparing Figs. 2A and 6A, and the fact that the contentious data in Figs. 2C and 6C of the above article had already been published prior to its submission to


Correction: Journal of Translational Medicine (2023) 21:157 10.1186/s12967-023-04011-yFollowing publication of the original article , we haveAcknowledgementsThe authors thank Alexey Zakharov, Jorge Neyra and Dac-Trung Nguyen for their thoughtful feedback and technical implementation as well as Richard Pacheco, Eduardo Luiggi, Carlin Biyoo, Ke Wang and Hugo Hernandez for infrastructure support.


In “Digital Phenotyping for Differential Diagnosis of Major Depressive Episode: Narrative Review”  the authors made three additions to the authorship list.The authorship is currently listed as:Eric Ettore, Philipp Müller, Jonas Hinze, Michel Benoit, Bruno Giordana, Danilo Postin, Amandine Lecomte, Hali Lindsay, Philippe Robert, Alexandra KönigAnd will be changed to read as follows:Eric Ettore, Philipp Müller, Jonas Hinze, Matthias Riemenschneider, Michel Benoit, Bruno Giordana, Danilo Postin, Rene Hurlemann, Amandine Lecomte, Michel Musiol, Hali Lindsay, Philippe Robert, Alexandra KönigThe authors who have been recently added are affiliated with the following institutions, which are already correctly presented in the affiliation list:3:Matthias RiemenschneiderDepartment of Psychiatry and Psychotherapy, Saarland University Medical Center, Hombourg, Germany.5:Rene HurlemannDepartment of Psychiatry, School of Medicine and Health Sciences, Carl von Ossietzky University of Oldenburg, Bad Zwischenahn, Germany.6:Michel MusiolResearch Department Sémagramme Team, Institut national de recherche en informatique et en automatique, Nancy, France.The correction will appear in the online version of the paper on the JMIR Publications website on April 12, 2023, together with the publication of this correction notice. Because this was made after submission to PubMed, PubMed Central, and other full-text repositories, the corrected article has also been resubmitted to those repositories.


In the original publication , there wTo the correct version appears below. The marker labels of DNA ladder in Figures 1–6 should be the same as those in the corrected In the original publication , there w“LP (backward loop primer)” in the fourth line of The corrected content appears below.There was an error in the original publication . “LF, anA correction has been made to Section 2.2. LAMP Reaction on page 2: T. tenax (GenBank Accession No. U86615) were designed using the software Primer explorer V.5 (http://primerexplorer.jp (accessed on 28 February 2020). These include FIP and BIP, F3 and B3, LF, and LB  was carried out on the closely related protozoan T. vaginalis, to check for specificity.The LAMP primers targeting the ITS and 5.8S rRNA gene of , and LB . MultiplThe authors state that the scientific conclusions are unaffected. This correction was approved by the Academic Editor. The original publication has also been updated.


NH2-UIO-66 (Zr), with a maximum emission wavelength of 455 nm under 350 nm excitation, was prepared using a microwave-assisted heating method. The NH2-UIO-66 (Zr)@MIP sensor with specific recognition sites for oxytetracycline was then acquired by modifying a molecularly imprinted polymer on the surface of NH2-UIO-66 (Zr). The introduction of NH2-UIO-66 (Zr) as both a signal tag and supporter can strengthen the sensitivity of the fluorescence sensor. Thanks to the combination of the unique characteristics of the molecularly imprinted polymer and NH2-UIO-66 (Zr), the prepared sensor not only exhibited a sensitive fluorescence response, specific identification capabilities and a high selectivity for oxytetracycline, but also showed good fluorescence stability, satisfactory precision and reproducibility. The fabricated sensor displayed a fluorescent linear quenching in the OTC concentration range of 0.05–40 μg mL−1, with a detection limit of 0.012 μg mL−1. More importantly, the fluorescence sensor was finally applied for the detection of oxytetracycline in milk, and the results were comparable to those obtained using the HPLC approach. Hence, the NH2-UIO-66 (Zr)@MIP sensor possesses great application potential for the accurate evaluation of trace oxytetracycline in dairy products.Developing sensitive and effective methods to monitor oxytetracycline residues in food is of great significance for maintaining public health. Herein, a fluorescent sensor (NH As a result, the establishment of LMOF-based sensors with specific recognition abilities and high selectivity is a vital method by which to achieve the accurate evaluation of target analytes in real samples.Luminescent metal organic frameworks (LMOFs), as rapidly developing novel-type organic–inorganic porous crystal materials, have displayed wide application potential in sensing fields owing to their high specific surface area and porosity, intrinsic luminescence properties, as well as structure multiplicity ,2. Amongace area ,4,5,6. Ft effect . Wang et in milk . Althoug2-UIO-66 (Zr) with MIP in order to design fluorescent sensors, in which the introduction of MIP can promote the generation of customized binding sites complementary to the target analytes in terms of size, shape and functional group, thus improving the selectivity of the obtained sensor. For example, a MOF@MIP FL sensor (NH2-UIO-66@MIP), synthetized by encapsulating NH2-UIO-66 into the MIP, was successfully exploited for the ultrasensitive and highly selective detection of melatonin in juice [2-UIO-66/MIP) was constructed to selectively and effectively detect trace levels of 4-nitrophenol in drinkable water, as well as in environmental water [2-UIO-66) was made via decorating MIP on Zr-LMOF and was employed for the FL sensing of chloramphenicol in animal-derived food [Molecular imprinting technology (MIT) is a promising molecular simulation recognition technique that mimics the specific antigen–antibody or enzyme–substrate binding processes, and has attracted great attention in the past few decades. The formed molecularly imprinted polymer (MIP) not only possesses the ability to specifically recognize the detected molecules, but also has a high adsorption efficiency and strong stability, which makes it widely used in various fields  ,10,11,12in juice . A LMOF-al water . A turn-ved food . Therefo−1, respectively [For many decades, the abuse of antibiotics has been regarded as a global concern because antibiotic residues may constitute a threat to human health ,17. Oxytectively ,23,24. Aectively , liquid ectively , enzyme-ectively , high-peectively , fluoromectively  and so oectively ,31,32. H2-UIO-66 (Zr) for the selective and ultrasensitive FL monitoring of OTC. Consequently, in this work, a turn-off FL sensor (expressed as NH2-UIO-66 (Zr)@MIP) that combines a large surface area and the unique fluorescence properties of NH2-UIO-66 (Zr), as well as the high specificity of the imprinted layer, was developed for an assay of OTC using the inner filter effect (IFE). Herein, the NH2-UIO-66 (Zr) with an intense blue FL emission, as a signal tag and substrate material, was prepared via a simple microwave-assisted heating process and then covered with a molecularly imprinted layer. After removing the OTC template molecule, the NH2-UIO-66 (Zr)@MIP sensor with custom-made binding sites for the OTC was obtained. The modification of the MIP granted the sensor high selectivity, adsorption affinity and binding efficiency to OTC. Meanwhile, NH2-UIO-66 (Zr), as a luminous center and a carrier, endowed the proposed sensor with a desirable FL signal output and response sensitivity. Furthermore, its relatively uniform morphology, good optical properties, superior FL sensitivity, outstanding adsorption and binding performance, as well as its excellent specificity, were demonstrated via different characterizations. The established sensor was successfully used in the highly sensitive and selective determination of OTC in milk samples, confirming its practical applicability.Although some FL sensors that integrate the merits of LMOFs and MIP have been designed ,33,34,354, 99%) was purchased from Beijing Yinuokai Technology Co., Ltd. . Methacrylic acid , 2,2-azobisisobutyronitrile  and ethylene glycol dimethacrylate  were obtained from TCI Development Co., Ltd. . N, N-dimethylformamide (DMF), ethanol, glucose, sucrose, MnCl2·4H2O, MgCl2·6H2O, Zn(NO3)2·6H2O, CaCl2, NaCl and KCl were supplied by Sinopharm Chemical Reagent Co., Ltd. . All reagents and chemicals used in this work were of at least analytical grade. The apparatuses utilized in this study are described in detail in the 2-aminoterephthalic acid , tetracycline , doxycycline , oxytetracycline , chlortetracycline , chloramphenicol , tyrosine (Tyr), histidine (His), serine (Ser), phenylalanine (Phe), arginine (Arg) and cysteine (Cys) were provided by Shanghai Macklin Biochemical Co., Ltd. . Zirconium chloride (ZrCl2-UIO-66 (Zr) refers to the microwave-assisted heating assay employed in a previous study with minor changes [4 and 500 mg of ATA were firstly dissolved in 60 mL of DMF, followed by ultrasonic treatment for 1 h. Next, the aforementioned reaction precursor solution was placed in a stainless steel Teflon-lined autoclave and heated to 120 °C for 24 h. After natural cooling, the deposition was attained via centrifugation, distributed in ethanol (30 mL), and heated at 100 °C for 30 min in a microwave synthesis reaction device. Subsequently, after dropping to ambient temperature, the obtained solid was centrifuged, and then the above microwave heating activation process was carried out again. Ultimately, the yellow product was acquired via vacuum drying (60 °C for 6 h) for later tests.The preparation process of NH2-UIO-66 (Zr)@MIP was fabricated according to a previous study, with slight modifications [2-UIO-66 (Zr)  and OTC  were completely dispersed in 30 mL of ethanol using ultrasonic treatment. Then, after the addition of MAA , the mixture was pre-polymerized for 50 min under continuous stirring. Subsequently, EGDMA  and AIBN  were successively introduced into the above synthesis system and stirred for 15 h in a water bath at 65 °C. Finally, the acquired polymer was centrifuged, eluted repeatedly via water/ethanol  to expunge OTC and dried under vacuum at 50 °C for 7 h. Meanwhile, the non-imprinting polymer (NH2-UIO-66 (Zr)@NIP), as a contrast material, was prepared according to the above steps in addition to not adding OTC.NHications . In the 2-UIO-66 (Zr)@MIP or NH2-UIO-66 (Zr)@NIP was scattered in 4 mL of PBS buffer solution (pH = 7) with various concentrations of OTC. After incubation for 30 min, the FL determination was performed under an excitation wavelength of 350 nm and the FL intensity of the sensing system at 455 nm was obtained. The specific recognition performance was appraised by adding other antibiotics with a similar structure or possible coexisting interfering substances instead of OTC under identical experimental conditions. The measurements of each experiment were carried out in triplicate.In brief, 1 mg of NH2-UIO-66 (Zr)@MIP, by spiking the proper concentration of OTC. Three parallel experiments were conducted on the milk samples of each concentration.Fresh pure milk bought from a local supermarket  was used to assess the practicability of the proposed FL method based on NH−1, 1 μg mL−1, 15 μg mL−1 and 25 μg mL−1) were vortically mingled with 4 mL of acetonitrile for 5 min. Subsequently, the mixture was centrifuged and the resulting supernatant was filtrated using a 0.22 μm microfilter to expunge protein precipitates. Finally, the above samples were dried using nitrogen and re-dispersed in 1 mL of PBS buffer solution (pH = 7) for FL determination.The spiked milk samples containing specific OTC concentrations were first prepared and placed overnight. Afterwards, the preprocessing of the samples was executed according to a previous study . In brieWith regard to HPLC determination, the extraction, purification and analysis procedures of milk samples were carried out according to Chinese National Standards (GB/T 22990-2008) , which w2-UIO-66 (Zr) with a bright blue fluorescence and large surface area was first fabricated via a self-assembly strategy using Zr4+ and ATA as precursors. Subsequently, a new biomimetic FL sensor based on MIP-coated NH2-UIO-66 (Zr) was prepared using the one-step aggregation method. The polymerization reaction was thermally initiated and completed in a water bath in the presence of OTC (template), NH2-UIO-66 (Zr) (fluorophore and supporter), MAA , EGDMA (cross-linker) and AIBN (initiator). During this process, OTC molecules and functional monomers were combined by hydrogen bonds. After eliminating the imprinted template OTC by using a suitable eluent, the NH2-UIO-66 (Zr)@MIP sensor with specific recognition cavities fitting the shape and functional group of OTC was finally achieved in order to selectively monitor the OTC. The existence of NH2-UIO-66 (Zr) as both a signal transducer and carrier granted the proposed sensor outstanding FL characteristics and good response sensitivity. The introduction of a molecularly imprinted layer not only preserved the sensitive FL signal of NH2-UIO-66 (Zr), but also endowed the obtained sensor with the ability to specifically recognize OTC. Consequently, the constructed NH2-UIO-66 (Zr)@MIP sensor integrated these superiorities of LMOFs and MIP. Moreover, in order to obtain NH2-UIO-66 (Zr)@MIP with an excellent fluorescent response and the ability to bind well to the OTC, the synthesis conditions, including the additive level of fluorophore, the molar ratio of OTC, MAA and EGDMA, and the polymerization time, were optimized (As portrayed in ptimized .2-UIO-66 (Zr), NH2-UIO-66 (Zr)@MIP and NH2-UIO-66 (Zr)@NIP were observed via SEM and TEM. SEM (2-UIO-66 (Zr) presented a uniform and smooth octahedron-like appearance, with a mean size of nearly 50 nm [2-UIO-66 (Zr) was also explored via the energy-dispersive spectrometer (EDS) spectrum (2-UIO-66 (Zr). These results demonstrated the successful synthesis of NH2-UIO-66 (Zr). As displayed in 2-UIO-66 (Zr)@MIP and NH2-UIO-66 (Zr)@NIP) appeared nearly spherical, with a particle size of approximately 250 nm (2-UIO-66 (Zr) due to the introduction of the molecular imprinting layer. The TEM images (2-UIO-66 (Zr) and possessed an archetypal core-shell structure, which evidenced that the polymers were successfully formed. In addition, the element mapping image of NH2-UIO-66 (Zr)@MIP (2-UIO-66 (Zr)@MIP sensor.The surface morphologies and structures of the fabricated NHTEM. SEM a, TEM @MIP  showed t2-UIO-66 (Zr), the characteristic peaks at 3492 and 3373 cm−1 can be attributed to the antisymmetric and symmetric stretching modes of -NH2, respectively [−1 originated from a C=C stretching vibration in the benzene ring of the ATA ligand [−1), Zr–O (483 cm−1) and -OCO (1430 and 1384 cm−1) were also observed, indicating that the dehydroxylation phase in NH2-UIO-66 (Zr) was favorably formed thanks to the coordination of Zr4+ with ATA [2-UIO-66 (Zr)@NIP, the absorption peaks at 3544 cm−1 (-OH), 2988 and 2953 cm−1 (C=H), 1731 cm−1 (C=O), 1455 cm−1 (C=C), and 1260 and 1159 cm−1 (C–O–C) symbolized the presence of MAA  and EGDMA (cross-linker). Meanwhile, the Zr–O vibration peaks  corresponding to the NH2-UIO-66 (Zr) appeared in NH2-UIO-66 (Zr)@NIP, which demonstrated the successful preparation of the non-imprinted polymer doped with NH2-UIO-66 (Zr) [2-UIO-66 (Zr)@MIP spectrum were very similar to those in the NH2-UIO-66 (Zr)@NIP spectrum, implying that NH2-UIO-66 (Zr)@MIP was triumphantly developed.The FT–IR spectra were recorded in order to analyze the surface chemistry of the synthetic materials. As presented in ectively ,40. The A ligand ,15. The with ATA . For NH21430 and 84 cm−1 w-66 (Zr) . Additio2-UIO-66 (Zr) highly coincided with those reported in the literature, which showed that NH2-UIO-66 (Zr) with good crystallinity was triumphantly fabricated [2-UIO-66 (Zr)@MIP and NH2-UIO-66 (Zr)@NIP, the characteristic absorption peaks associated with NH2-UIO-66 (Zr) became unapparent, owing to the decoration of the surface molecularly imprinted shell, which helped to prove the successful preparation of the polymers [To analyze the crystallographic structure of the synthesized materials, XRD data were collected and are depicted in bricated ,14,43. Npolymers .2 adsorption/desorption isotherms of NH2-UIO-66 (Zr) and its imprinted polymer were evaluated, as shown in 2-UIO-66 (Zr), NH2-UIO-66 (Zr)@MIP and NH2-UIO-66 (Zr)@NIP, obtained via the Brunauer–Emmett–Teller (BET) analysis method, were 219 m2 g−1, 37 m2 g−1 and 28 m2 g−1, respectively. Compared to NH2-UIO-66 (Zr), the surface areas of NH2-UIO-66 (Zr)@MIP and NH2-UIO-66 (Zr)@NIP were clearly reduced after coating the imprinted layer [2-UIO-66 (Zr)@MIP in comparison to that of NH2-UIO-66 (Zr)@NIP, probably due to the existence of imprinted cavities after eliminating the template [In order to further investigate the surface characteristics of the resulting materials, the Ned layer ,35,45. Mtemplate .2-UIO-66 (Zr)@MIP) was triumphantly fabricated via combining the molecularly imprinted polymer with NH2-UIO-66 (Zr).The above-mentioned data signified that the FL sensor (NH2-UIO-66 (Zr)@MIP showed slightly lower FL intensity than NH2-UIO-66 (Zr) on account of decorating the MIP layer. However, NH2-UIO-66 (Zr)@MIP exhibited an intense symmetric FL emission peak corresponding to NH2-UIO-66 (Zr) at 455 nm under 350 nm excitation, which implied that the modification of the surface imprinting layer had no remarkable impact on the FL performance of NH2-UIO-66 (Zr). As a consequence, the synthesized sensor maintained the unique luminous property of NH2-UIO-66 (Zr).The luminescence performance of the developed sensor was firstly studied through FL spectra. As displayed in 2-UIO-66 (Zr)@MIP and NH2-UIO-66 (Zr)@NIP) to OTC were then conducted to explore the practicability of the established sensor (2-UIO-66 (Zr)@MIP presented a more conspicuous FL change than NH2-UIO-66 (Zr)@NIP, owing to its better binding capacity and specificity towards OTC. After eliminating OTC, the fluorescence of the polymers was restored and the FL spectrum of NH2-UIO-66 (Zr)@MIP was basically consistent with that of NH2-UIO-66 (Zr)@NIP, which indicated that the fabricated NH2-UIO-66 (Zr)@MIP sensor was viable for the determination of OTC.FL experiments measuring the response of the polymers (NHd sensor a. ClearlF0/F) of NH2-UIO-66 (Zr)@MIP and NH2-UIO-66 (Zr)@NIP towards the target OTC at different incubation times was recorded. Under the continuously increasing reaction time, the F0/F value of NH2-UIO-66 (Zr)@MIP increased quickly at first, reached the maximum at 30 min, and then tended to remain unchanged, which demonstrated that the detection system achieved adsorption equilibrium within 30 min. Therefore, 30 min was considered to be the optimal reacting time in consequent trials. The variation in the trend observed with regard to the FL response of NH2-UIO-66 (Zr)@NIP was analogous to NH2-UIO-66 (Zr)@MIP. Nevertheless, NH2-UIO-66 (Zr)@MIP possessed a higher FL response and adsorption efficiency than NH2-UIO-66 (Zr)@NIP at the identical reaction time, indicating that the generation of specific identification imprinted sites enhanced the binding affinity of NH2-UIO-66 (Zr)@MIP towards OTC.Adsorptive kinetics tests of the as-prepared polymers were performed to investigate the adsorption performance of the sensor. As shown in 2-UIO-66 (Zr)@MIP and the FL response of NH2-UIO-66 (Zr)@MIP towards OTC were studied in the case of not adding and adding OTC, respectively. As illustrated in 2-UIO-66 (Zr)@MIP first increased, then remained basically stable, and the highest FL intensity was apparently observed at pH = 7. In addition, the maximum FL response value (F0/F) was concurrently obtained at pH = 7, proving that NH2-UIO-66 (Zr)@MIP possessed the strongest adsorption binding efficiency to OTC. Thus, pH = 7 was chosen as the best pH for the sensing system in subsequent FL detection experiments.Next, the influences of the pH (5–9) on the fluorescence intensity of NH2-UIO-66 (Zr)@MIP under diverse ultraviolet (UV) light radiation times and storing times. As shown in 2-UIO-66 (Zr)@MIP exhibited an unapparent FL change after UV irradiation at 350 nm for 60 min, signifying the exceptional photo-bleaching resistance of the proposed NH2-UIO-66 (Zr)@MIP-based sensor. At the same time, the FL intensity of NH2-UIO-66 (Zr)@MIP remained steady within 60 days @MIP-based sensor had good optical properties and a good adsorption performance.The above experimental results confirm that the NH2-UIO-66 (Zr)@MIP and NH2-UIO-66 (Zr)@NIP after the addition of different levels of OTC. As portrayed in −1, the FL intensity of NH2-UIO-66 (Zr)@MIP was progressively quenched. Clearly, NH2-UIO-66 (Zr)@NIP showed an analogous FL change trend towards NH2-UIO-66 (Zr)@MIP. Nevertheless, compared with NH2-UIO-66 (Zr)@NIP, NH2-UIO-66 (Zr)@MIP presented a more noticeable FL quenching response when the same concentration of OTC was added (2-UIO-66 (Zr)@MIP. Furthermore, the relationship between the FL quenching signal (F0/F) and the concentration of OTC can be described via the Stern–Volmer equation [COTC and SVK are the concentration of OTC and the FL quenching constant, respectively. F0 and F represent the FL intensity of the sensing system before and after adding OTC. The imprinting factor (IF), set as the specific value of KSV, NH2-UIO-66 (Zr)@MIP to KSV, NH2-UIO-66 (Zr)@NIP, was used as a key index to estimate the adsorption binding capacity of the NH2-UIO-66 (Zr)@MIP sensor towards OTC.Under the above optimum sensing conditions, the concentration responses of the as-synthesized FL polymers for OTC were assessed by collecting and analyzing the FL spectra of NHas added b, which equation ,47:F0/F 2-UIO-66 (Zr)@MIP and the OTC concentration (0.05–40 μg mL−1). The limit of detection (LOD) of 0.012 μg mL−1 was achieved on the basis of the standard 3bS/slope  [2-UIO-66 (Zr)@MIP had a more notable FL response change than NH2-UIO-66 (Zr)@NIP at an identical OTC dose, which emphasized the outstanding selectivity and adsorptive efficiency of NH2-UIO-66 (Zr)@MIP towards OTC. Simultaneously, the good specific recognition capacity of NH2-UIO-66 (Zr)@MIP was also authenticated by comparing the slopes of the corresponding standard linear equations of NH2-UIO-66 (Zr)@MIP  and NH2-UIO-66 (Zr)@NIP  @MIP sensor had a superior selective identification capacity and superior adsorption affinity for OTC., n = 9) ,48. Plai= 0.994) c,d. More2-UIO-66 (Zr)@MIP sensor towards the OTC molecule was investigated and discussed. The FL spectrum of NH2-UIO-66 (Zr)@MIP and the UV absorption spectrum of OTC are illustrated in 2-UIO-66 (Zr)@MIP almost did not overlap with the UV absorption spectrum of OTC, but there was a partial and effective overlap between the excitation spectrum of NH2-UIO-66 (Zr)@MIP and the UV absorption band of OTC. Therefore, the possible mechanism was initially determined as the inner filter effect (IFE), rather than FL resonance energy transfer (FRET) [2-UIO-66 (Zr)@MIP before and after OTC adsorption was analyzed. The FL emission decay curves are presented in 2-UIO-66 (Zr)@MIP showed a slight variation from 3.61 ns to 3.48 ns after OTC treatment, further demonstrating that the OTC-initiated FL quenching behavior was mainly caused by IFE.The potential FL sensing mechanism of the NHr (FRET) ,49. To br (FRET) ,51. Acco2-UIO-66 (Zr)@MIP-based sensor towards the OTC molecule to be better understood. As presented in 2-UIO-66 (Zr)@MIP was notably greater than that of other antibiotics with a similar structure, which was mainly owing to the formation of the special recognition cavities in NH2-UIO-66 (Zr)@MIP that utterly conformed the size, shape and functional group of OTC during the molecular imprinting process. Because there were no specific recognition sites corresponding to TET, DOX, CTC and CAP in NH2-UIO-66 (Zr)@MIP, the NH2-UIO-66 (Zr)@MIP sensor had a comparatively small FL response value (F0/F) to these analogs (2-UIO-66 (Zr)@MIP to selectively capture and effectively bind with these analogues in the detection process. Furthermore, compared with NH2-UIO-66 (Zr)@MIP, NH2-UIO-66 (Zr)@NIP, without specific recognition sites, generated a relatively low FL response to OTC and other analogues, which was attributed to the nonspecific adsorption between NH2-UIO-66 (Zr)@NIP and these analytes. The above results suggest that the introduction of highly selective imprinted sites endowed the NH2-UIO-66 (Zr)@MIP sensor with the ability to specifically identify OTC.The selectivity of the constructed FL sensing system was assessed by recording and contrasting the FL changes in the polymers to OTC and its structural analogues . The chemical structures of these mentioned antibiotics, which are first portrayed in  analogs b. TherefF0/F) of NH2-UIO-66 (Zr)@MIP to different concentrations of structural analogues were also studied to investigate the selectivity of the established sensor. As shown in F0/F) apparently increased after introducing OTC. In addition, there was no significant linear relationship between the concentration of the analogue and FL change (F0/F), which indicated that the constructed FL detection system had good selectivity for the target OTC.The FL response changes (2-UIO-66 (Zr)@MIP to specifically recognize OTC, a competitive adsorption test was conducted by adding the possible coexisting structural analogs  into the mixed system containing NH2-UIO-66 (Zr)@MIP and OTC. As revealed in 2-UIO-66 (Zr)@MIP displayed tiny FL variation even though the concentration of each analogue was twice that of OTC, demonstrating that the interference caused by the presence of the coexisting analogues in the sensing system was inconspicuous. The good specificity of NH2-UIO-66 (Zr)@MIP towards OTC was probably due to the existence of OTC-imprinted sites generated via hydrogen bond interaction, which improved the combination efficiency of the sensor to OTC, and inhibited the nonspecific adsorption of the coexisting analogs. Thus, the obtained sensor possessed gratifying selectivity and specificity for the target OTC.In order to further assess the ability of NH−, NO3−, K+, Na+, Ca2+, Zn2+, Mg2+, and Mn2+) and common amino acids , will directly influence the accuracy of the test results. Therefore, the ability of the NH2-UIO-66 (Zr)@MIP sensor to avoid interference was explored by introducing the above interfering analytes into the constructed FL sensing system in the presence and absence of OTC. As shown in −1 (5 times of OTC concentration), but the influence of these interfering substances on the FL intensity of NH2-UIO-66 (Zr)@MIP was minor, which was in accordance with the blank experimental group. After adding OTC, the FL of the sensing system was significantly quenched, indicating that these interfering species had a negligible effect on the FL detection of OTC. The above results indicated that the developed FL sensor exhibited excellent selectivity and specificity towards OTC, as well as superior anti-interference characteristics in a complicated environment, thus providing a feasible tool for the FL detection of OTC.Due to the matrix complexity of the practical samples, the potential coexisting interfering substances in the real detection process, such as sugars (glucose and sucrose), ions (Cl2-UIO-66 (Zr)@MIP method and HPLC means. Consequently, the spiking and recovery tests were performed by introducing different levels of OTC standards  into the milk samples, and the relevant analysis results are presented in The commercial milk bought from the local supermarket was taken as a practical sample in order to analyze and authenticate the applicability of the FL sensing approach created in this study. No OTC was found in the blank milk samples when using the NH2-UIO-66 (Zr)@MIP sensing method were also appraised by detecting the spiked samples using different concentrations of OTC standards . As shown in n = 6), respectively, indicating that the sensor had sterling reproducibility as well as good accuracy, and was suitable for the determination of OTC in real products.The intra-day and inter-day precisions of the established NH−1), a lower LOD (0.012 μg mL−1), a comparable recovery rate (93.56–98.21%) and an acceptable accuracy (RSD < 2.59%). The good performance of the NH2-UIO-66 (Zr)@MIP-based sensor came from the following aspects. On one hand, introducing NH2-UIO-66 (Zr), which has sterling FL characteristics and a large surface area, as the support improved the sensitivity of the proposed FL sensor. On the other hand, the integration of the surface-imprinted layer endowed the sensor with the ability to specifically identify and accurately absorb the target from the complicated matrix, which helped to avoid the tedious sample pretreatment process and to reduce the analysis time. Taken together, the constructed NH2-UIO-66 (Zr)@MIP-based sensor can be appropriately applied in order to quantitatively monitor trace OTC in a sophisticated system.The performance of the designed sensing assay was compared to some subsistent FL-based methods for OTC detection, the results of which are shown in 2-UIO-66 (Zr)@MIP) was successfully designed based on an amino-functionalized zirconium (IV) metal–organic framework embedded in a molecularly imprinted polymer in order to selectively recognize and sensitively detect trace OTC. Because of the combination of MIP, with an excellent specific recognition ability, and NH2-UIO-66 (Zr), with unique fluorescent characteristics, the fabricated NH2-UIO-66 (Zr)MIP sensor showed exceptional sensitivity, excellent selectivity, desirable anti-interference capacity, as well as good precision during the process of detecting OTC. Additionally, the constructed FL sensing system was triumphantly employed in order to determine OTC in milk with satisfying results, displaying good practical application prospects. Therefore, it is expected that the proposed NH2-UIO-66 (Zr)@MIP-based sensor will provide a significant detection platform for OTC residue analysis in food safety evaluation.In summary, a novel turn-off fluorescent biomimetic sensor (NH