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The cationic achiral and chiral terpyridine diphosphine ruthenium complexes [RuCl(PP)(tpy)]Cl (PP=dppp (1), (R,R)-Skewphos (2) and (S,S)-Skewphos (3)) are easily obtained in 85-88 % yield through a one-pot synthesis from [RuCl 2 (PPh 3 ) 3 ], the diphosphine and 2,2':6',2''-terpyridine (tpy) in 1-butanol. Treatment of 1-3 with NaPF 6 in methanol at RT affords quantitatively the corresponding derivatives [RuCl(PP)(tpy)]PF 6 (PP=dppp (1 a), (R,R)-Skewphos (2 a) and (S,S)-Skewphos (3 a)). Reaction of [RuCl 2 (PPh 3 ) 3 ] with (S,R)-Josiphos or (R)-BINAP in toluene, followed by treatment with tpy in 1-butanol and finally with NaPF 6 in MeOH gives [RuCl(PP)(tpy)]PF 6 (PP=(S,R)-Josiphos (4 a), (R)-BINAP (5 a)) isolated in 78 % and 86 % yield, respectively. The chiral derivatives have been isolated as single stereoisomers and 3 a, 4 a have been characterized by single crystal X-ray diffraction studies. The tpy complexes with NaOiPr display high photocatalytic activity in the transfer hydrogenation (TH) of carbonyl compounds using 2-propanol as the only hydrogen donor and visible light at 30 °C, at remarkably high S/C (up to 5000) and TOF values up to 264 h -1 . The chiral enantiomers 2, 2 a and 3, 3 a induce the asymmetric photocatalytic TH of acetophenone, affording (S)- and (R)-1-phenylethanol with 51 and 52 % ee, respectively, in a MeOH/2-propanol mixture., (© 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

The chiral cationic complex [Ru(η 1 -OAc)(CO)((R,R)-Skewphos)(phen)]OAc (2 R ), isolated from reaction of [Ru(η 1 -OAc)(η 2 -OAc)(R,R)-Skewphos)(CO)] (1 R ) with phen, reacts with NaOPiv and KSAc affording [RuX(CO)((R,R)-Skewphos)(phen)]Y (X=Y=OPiv 3 R ; X=SAc, Y=OAc 4 R ). The corresponding enantiomers 2 S -4 S have been obtained from 1 S containing (S,S)-Skewphos. Reaction of 2 R and 2 S with (S)-cysteine and NaPF 6 at pH=9 gives the diastereoisomers [Ru((S)-Cys)(CO)(PP)(phen)]PF 6 (PP=(R,R)-Skewphos 2 R -Cys; (S,S)-Skewphos 2 S -Cys). The DFT energetic profile for 2 R with (S)-cysteine in H 2 O indicates that aquo and hydroxo species are involved in formation of 2 R -Cys. The stability of the ruthenium complexes in 0.9 % w/v NaCl solution, PBS and complete DMEM medium, as well as their n-octanol/water partition coefficient (logP), have been evaluated. The chiral complexes show high cytotoxic activity against SW1736, 8505 C, HCT-116 and A549 cell lines with EC 50 values of 2.8-0.04 μM. The (R,R)-Skewphos derivatives show higher cytotoxicity compared to their enantiomers, 4 R (EC 50 =0.04 μM) being 14 times more cytotoxic than 4 S against the anaplastic thyroid cancer 8505 C cell line., (© 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

The diacetate complexes trans -[Ru(κ 1 -OAc) 2 (PPh 3 ) 2 (NN)] (NN = ethylenediamine (en) ( 1 ), 2-(aminomethyl)pyridine (ampy) ( 2 ), 2-(aminomethyl)pyrimidine (ampyrim) ( 3 )) have been isolated in 76-88% yield by reaction of [Ru(κ 2 -OAc) 2 (PPh 3 ) 2 ] with the corresponding nitrogen ligands. The ampy-type derivatives 2 and 3 undergo isomerization to the thermodynamically most stable cationic complexes [Ru(κ 1 -OAc)(PPh 3 ) 2 (NN)]OAc ( 2a and 3a ) and cis -[Ru(κ 1 -OAc) 2 (PPh 3 ) 2 (NN)] ( 2b and 3b ) in methanol at RT. The trans -[Ru(κ 1 -OAc) 2 (P 2 ) 2 ] (P 2 = dppm ( 4 ), dppe ( 5 )) compounds have been synthesized from [Ru(κ 2 -OAc) 2 (PPh 3 ) 2 ] by reaction with the suitable diphosphine in toluene at 95 °C. The complex cis -[Ru(κ 1 -OAc) 2 (dppm)(ampy)]( 6 ) has been obtained from [Ru(κ 2 -OAc) 2 (PPh 3 ) 2 ] and dppm in toluene at reflux and reaction with ampy. The derivatives trans -[Ru(κ 1 -OAc) 2 P 2 (NN)] ( 7 - 16 ; NN = en, ampy, ampyrim, 8-aminoquinoline; P 2 = dppp, dppb, dppf, ( R )-BINAP) can be easily synthesized from [Ru(κ 2 -OAc) 2 (PPh 3 ) 2 ] with a diphosphine and treatment with the NN ligands at RT. Alternatively these compounds have been prepared from trans -[Ru(OAc) 2 (PPh 3 ) 2 (NN)] by reaction with the diphosphine in MEK at 50 °C. The use of ( R )-BINAP affords trans -[Ru(κ 1 -OAc) 2 (( R )-BINAP)(NN)] (NN = ampy ( 11 ), ampyrim ( 15 )) isolated as single stereoisomers. Treatment of the ampy-type complexes 8 - 15 with methanol at RT leads to isomerization to the cationic derivatives [Ru(κ 2 -OAc)P 2 (NN)]OAc ( 8a - 15a ; NN = ampy, ampyrim; P 2 = dppp, dppb, dppf, ( R )-BINAP). Similarly to 2 , the dipivalate trans -[Ru(κ 1 -OPiv) 2 (PPh 3 ) 2 (ampy)] ( 18 ) is prepared from [Ru(κ 2 -OPiv) 2 (PPh 3 ) 2 ] ( 17 ) and ampy in CHCl 3 . The pincer acetate [Ru(κ 1 -OAc)(CNN OMe )(PPh 3 ) 2 ] ( 19 ) has been synthesized from [Ru(κ 2 -OAc) 2 (PPh 3 ) 2 ] and HCNN OMe ligand in 2-propanol with NEt 3 at reflux. In addition, the dppb pincer complexes [Ru(κ 1 -OAc)(CNN)(dppb)] (CNN = AMTP ( 20 ), AMBQ Ph ( 21 )) have been obtained from [Ru(κ 2 -OAc) 2 (PPh 3 ) 2 ], dppb, and HAMTP or HAMBQ Ph with NEt 3 , respectively. The acetate NN and pincer complexes are active in transfer hydrogenation with 2-propanol and hydrogenation with H 2 of carbonyl compounds at S/C values of up to 10000 and with TOF values of up to 160000 h -1 ., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

The cationic acetate ruthenium complex [Ru(η1-OAc)(CO)(dppb)(phen)]OAc (1) is easily prepared in 83% yield from [Ru(η1-OAc)(η2-OAc)(CO)(dppb)] (dppb = 1,4-bis(diphenylphosphino)butane) and 1,10-phenanthroline (phen) in MeOH. The derivative 1 undergoes easy substitution of the coordinated acetate by reaction with NaOPiv, KSAc, and KSCN in MeOH, affording the corresponding complexes [RuX(CO)(dppb)(phen)]X (X = OPiv, 2; SAc, 3; and NCS, 4), whereas its reaction with NaCl and NH4PF6 affords [RuCl(CO)(dppb)(phen)]PF6 (5). Carboxylate complexes 1 and 2 show high solubility in water, enabling easy exchange of the coordinated carboxylate by water and other ligands (CH3CN, glutathione). Cationic complexes 1-5, compared to Cisplatin, display a strong cell viability decrease in two human anaplastic thyroid cancer cell lines (SW1736 and 8505C), ranging from 3.10 μM to 0.09 μM EC50 values. The most active compounds 1-3 show a marked increment of apoptosis and decrease of cancer cell aggressiveness, making them promising candidates for further evaluation studies.

The ligand HCNNOMe (6-(4-methoxyphenyl)-2-aminomethylpyridine) is easily prepared from the commercially available 6-(4-methoxyphenyl)pyridine-2-carbaldehyde by the reaction of hydroxylamine and hydrogenation (H2, 1 atm) with Pd/C. The pincer complexes cis-[RuCl(CNNOMe)(PPh3)2] (1) and [RuCl(CNNOMe)(PP)] (PP = dppb, 2; and dppf, 3) are synthesized from [RuCl2(PPh3)3], HCNNOMe and PP (for 2 and 3) in 2-propanol with NEt3 at reflux and are isolated in 85-93% yield. Carbonylation of 1 (CO, 1 atm) gives [RuCl(CNNOMe)(CO)(PPh3)] (4) (79% yield) which cleanly reacts with Na[BArf4] and PCy3, affording the cationic trans-[Ru(CNNOMe)(CO)(PCy3)(PPh3)][BArf4] (5) (92% yield). These robust pincer complexes display remarkably high catalytic activity in the transfer hydrogenation (TH) of lignocellulosic biomass carbonyl compounds, using 2-propanol at reflux in a basic medium (NaOiPr or K2CO3). Thus, furfural, 5-(hydroxymethyl)furfural and Cyrene are reduced to the corresponding alcohols with 2 and 3, at S/C in the range of 10 000-100 000, within minutes or hours (TOF up to 1 500 000 h-1). The monocarbonyl complex 5 was found to be extremely active in the TH of cinnamaldehyde, vanillin derivatives and ethyl levulinate at S/C in the range of 10 000-50 000. Vanillyl alcohol is also obtained by the TH of vanillin with 5 (S/C = 500) in 2-propanol in the presence of K2CO3.

Monocarbonyl complexes [RuCl 2 (CO)(PR 3 )(NN)] (R = Cy, NN = en 1, ampy 2; R = iPr; NN = en 3) have been prepared in a one pot reaction from [RuCl 2 (CO)(dmf)(PPh 3 ) 2 ], PR 3 and the NN ligand in CH 2 Cl 2 . Treatment of [Ru(OAc) 2 (CO)(PPh 3 ) 2 ] with NN ligands in methanol gives the cationic derivatives [Ru(OAc)(CO)(PPh 3 )(NN)]OAc (NN = en 4, ampy 5) in which one acetate acts as a bidentate ligand, whereas the other is not coordinated. Diphosphine complexes [RuCl 2 (CO)(PP)(PPh 3 )] (PP = dppb 6, dppf 7, (R)-BINAP 8, (R,S p )-Josiphos 9 and (R,R)-Skewphos 10) have been obtained starting from [RuCl 2 (CO)(dmf)(PPh 3 ) 2 ] and the PP ligand in CHCl 3 or toluene at reflux. The reaction of [Ru(OAc) 2 (CO)(PPh 3 ) 2 ] with PP in CH 2 Cl 2 or toluene affords the fluxional acetate derivatives [Ru(OAc) 2 (CO)(PP)] (PP = dppb 11, dppf 12, (R)-BINAP 13, and (R,R)-Skewphos 14). The cationic diphosphine complexes [RuCl(CO)(PP)(en)]Cl (PP = dppb 15, dppf 16) are prepared from [RuCl 2 (CO)(dmf)(PPh 3 ) 2 ], PP and en in CH 2 Cl 2 or, alternatively, from [RuCl 2 (CO) 2 ] n or the 6, 7 derivatives. Similarly, [Ru(OAc)(CO)(PP)(NN)]OAc (PP = dppb, NN = en 17, ampy 18; PP = dppf, NN = en 19, ampy 20) are isolated starting from [Ru(OAc) 2 (CO)(PPh 3 ) 2 ], PP and NN ligands or from 11, 12. The derivatives [Ru(OAc) 2 (CO)(PP)] show a fluxional behavior in solution as the result of the flexible coordination of acetate ligands. These complexes are found to be active in the transfer hydrogenation and hydrogenation of ketones and aldehydes, including furfural derivatives, at an S/C up to 10 000 and a TOF up to 18 000 h -1 .

The ATP binding site located on the subunit B of DNA gyrase is an attractive target for the development of new antibacterial agents. In recent decades, several small-molecule inhibitor classes have been discovered but none has so far reached the market. We present here the discovery of a promising new series of N-phenylpyrrolamides with low nanomolar IC 50 values against DNA gyrase, and submicromolar IC 50 values against topoisomerase IV from Escherichia coli and Staphylococcus aureus. The most potent compound in the series has an IC 50 value of 13 nM against E. coli gyrase. Minimum inhibitory concentrations (MICs) against Gram-positive bacteria are in the low micromolar range. The oxadiazolone derivative 11a, with an IC 50 value of 85 nM against E. coli DNA gyrase displays the most potent antibacterial activity, with MIC values of 1.56 μM against Enterococcus faecalis, and 3.13 μM against wild type S. aureus, methicillin-resistant S. aureus (MRSA) and vancomycin-resistant Enterococcus (VRE). The activity against wild type E. coli in the presence of efflux pump inhibitor phenylalanine-arginine β-naphthylamide (PAβN) is 4.6 μM., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)