Exploring the effect of the axial ligands on the anticancer activity of [C,N,N'] Pt(IV) cyclometallated compounds.

The synthesis of three novel [C,N,N'] Pt(IV) cyclometallated compounds containing hydroxo, dichloroacetato or trifluoroacetato axial ligands is reported. Compound [PtCl(OH){(CH)N(CH)NCH(4-FCH)}] (3) was prepared by the oxidative addition of hydrogen peroxide to [C,N,N'] Pt(II) cyclometallated compound [PtCl{(CH)N(CH)NCH(4-FCH)}] (1) and further the reaction of compound 3 with dichloroacetate or trifluoroacetate anhydrides led to the formation of the corresponding compounds [PtCl(CHClCOO){(CH)N(CH)NCH(4-FCH)}] (4) and [PtCl(CFCOO){(CH)N(CH)NCH(4-FCH)}] (5). The properties of the new compounds along with those of the compound [PtCl{(CH)N(CH)NCH(4-FCH)}] (2), including stability in aqueous media, reduction potential using cyclic voltammetry, cytotoxic activity against the HCT116 CRC cell line, DNA interaction, topoisomerase I and cathepsin inhibition, and computational studies involving reduction of the Pt(IV) compounds and molecular docking studies, are presented.

Toward Near-Infrared Emission in Pt(II)-Cyclometallated Compounds: From Excimers' Formation to Aggregation-Induced Emission.

Two series of Pt(II)-cyclometallated compounds containing N^C^N tridentate and alkynyl-chromophore ligands have been synthesized and structurally characterized. The N^C^N ligands differ on the presence of R = H or F in the central aromatic ring, while six different chromophores have been introduced to the alkynyl moiety. Single-crystal X-ray structures for some of the compounds reveal the presence of weak intermolecular contacts responsible for the formation of some dimers or aggregates.

Novel multifunctional and multitarget homo- (Fe) and heterobimetallic [(Fe,M) with M = Re or Mn] sulfonyl hydrazones.

The synthesis and characterization of the novel ferrocenyl sulfonyl hydrazide [Fe(η5-C5H5){(η5-C5H4)-S(O)2-NH-NH2}] (2) is reported. Additional studies on its reactivity using acetone or the ferrocenyl-, cyrhetrenyl- or cymantrenyl-aldehydes have allowed us to isolate and characterize [Fe(η5-C5H5){(η5-C5H4)-S(O)2-NH-N[double bond, length as m-dash]CMe2}] (3), the bis(ferrocenyl) derivative [Fe(η5-C5H5){[(η5-C5H4)-S(O)2-NH-N[double bond, length as m-dash]CH-(η5-C5H4)]Fe(η5-C5H5)}] (4) and the heterodimetallic compounds [Fe(η5-C5H5){[(η5-C5H4)-S(O)2-NH-N[double bond, length as m-dash]CH-(η5-C5H4)]M(CO)3}] with M = Re (5a) or Mn (5b). The X-ray crystal structures of compounds 3, 5a and 5b are also reported.

A novel type of organometallic 2-R-2,4-dihydro-1H-3,1-benzoxazine with R = [M(η-CH)(CO)] (M = Re or Mn) units. Experimental and computational studies of the effect of substituent R on ring-chain tautomerism.

The syntheses, characterization, X-ray crystal structures, electrochemical properties and anticancer and antichagasic activities of the first examples of 2-substituted 2,4-dihydro-1H-3,1-benzoxazines with half-sandwich organometallic arrays, [M(η5-C5H4)(CO)3] (M = Re or Mn), at position-2 are described. Experimental and computational studies based on DFT calculations on the open forms [Schiff bases of general formulae R-CH[double bond, length as m-dash]N-C6H4-2-CH2OH] (5), with R = ferrocenyl (a), phenyl (b), cyrhetrenyl (c) or cymantrenyl (d), and their tautomeric forms (2-substituted 2,4-dihydro-1H-3,1 benzoxazines) have allowed us to establish the influence of substituents a-d and solvents on: (a) the extent of tautomeric equilibria (5a-5d) ↔ (6a-6d) and (b) their electrochemical properties and the electronic distribution on the open and closed forms. Despite the formal similarity between 6c and 6d, their anticancer and antiparasitic activities are markedly different.

Isomeric and hybrid ferrocenyl/cyrhetrenyl aldimines: a new family of multifunctional compounds.

The synthesis and characterization of two novel and isomeric hybrid ferrocenyl/cyrhetrenyl aldimines [(η-CH)Fe{(η-CH)-CH[double bond, length as m-dash]N-(η-CH)}Re(CO)] (1) and [(η-CH)Fe{(η-CH)-N[double bond, length as m-dash]CH-(η-CH)}Re(CO)] (2) are reported. Their X-ray crystal structures reveal that both adopt the E form. However, molecules of 1 and 2 differ in the relative arrangement of the "Fe(η-CH)" and "Re(CO)" units (anti in 1 and syn in 2).

Neutral and ionic platinum compounds containing a cyclometallated chiral primary amine: synthesis, antitumor activity, DNA interaction and topoisomerase I-cathepsin B inhibition.

The synthesis and preliminary biological evaluation of neutral and cationic platinum derivatives of chiral 1-(1-naphthyl)ethylamine are reported, namely cycloplatinated neutral complexes [PtCl{(R or S)-NH(2)CH(CH(3))C(10)H(6)}(L)] [L = SOMe(2) ( 1-R or 1-S ), L = PPh(3) (2-R or 2-S), L = P(4-FC(6)H(4))(3) (3-R), L = P(CH(2))(3)N(3)(CH(2))(3) (4-R)], cycloplatinated cationic complexes [Pt{(R)-NH(2)CH(CH(3))C(10)H(6)}{L}]Cl [L = Ph(2)PCH(2)CH(2)PPh(2) (5-R), L = (C(6)F(5))(2)PCH(2)CH(2)P(C(6)F(5))(2) (6-R)] and the Pt(ii) coordination compound trans-[PtCl(2){(R)-NH(2)CH(CH(3))C(10)H(6)}(2)] (7-R). The X-ray molecular structure of 7-R is reported. The cytotoxic activity against a panel of human adenocarcinoma cell lines (A-549 lung, MDA-MB-231 and MCF-7 breast, and HCT-116 colon), cell cycle arrest and apoptosis, DNA interaction, topoisomerase I and cathepsin B inhibition, and Pt cell uptake of the studied compounds are presented.

Cyclopalladated primary amines: a preliminary study of antiproliferative activity through apoptosis induction.

Twelve cyclometallated palladium(II) complexes containing primary aromatic amines [benzylamine (a), (R)-1-(1-naphthyl)ethylamine (b) and 2-phenylaniline (c)] as anionic bidentate (C,N)(-) ligands have been evaluated against a panel of human adenocarcinoma cell lines (A549 lung, MDA-MB231 and MCF7 breast, and the cisplatin resistant HCT116 colon). The results revealed a remarkable antiproliferative activity of the triphenylphosphane mononuclear compounds 3-4 (series a, b, c) and the best inhibition was provided for 3c and 4c with the 2-phenylaniline ligand and a six membered chelate ring. Interestingly, 3c and 4c were 14 and 19 times more potent than cisplatin for the inhibition of the cisplatin resistant HCT116 human adenocarcinoma cell line, respectively.

Pt(II) complexes with (N,N') or (C,N,E)(-) (E=N,S) ligands: cytotoxic studies, effect on DNA tertiary structure and structure-activity relationships.

The cytotoxic activity of two series of platinum(II) complexes containing the polyfunctional imines R(1)-CHN-R(2) [R(1)=phenyl or ferrocenyl unit and R(2)=(CH2)n-CH2-NMe2 where n=1 or 2) (1 and 2) or C6H4-2-SMe (3)] acting as a bidentate (N,N') (4-7) or terdentate [C(phenyl or ferrocenyl),N,N'](-) (8-10) or [C(ferrocenyl),N,S](-) ligand (11) in front of A549 lung, MDA-MB231 breast and HCT116 colon human adenocarcinoma cell lines is reported. The results reveal that most of the platinum(II) complexes are active against the three assayed lines and compounds 6, 7 and the platinacycles 10 and 11 exhibit a remarkable antiproliferative activity, even greater than cisplatin itself, in the cisplatin resistant HCT116 human cancer cell line. Electrophoretic DNA migration studies showed that most of them modify the DNA tertiary structure in a similar way as the reference cisplatin.

Study of the effect induced by the substituents on the ring-chain tautomerism of Schiff bases derived from norephedrine.

The solution behavior and the spectroscopic properties of the novel Schiff bases (1S,2R)-R(1)CH=NCH(Me)CH(OH)Ph [with R(1) = ferrocenyl-[Fc (2b)], 5- or 3-methylthienyl [hereafter referred to as 5-MeTf and 3-MeTf (2c and 2d), respectively]] are reported. NMR studies show the existence of a tautomeric equilibrium between these imine forms (2b-d) and 2-substituted 4-methyl-5-phenyloxazolidines. The comparison of the results reveals that the molar ratios imine/oxazolidines (K): (a) are solvent and temperature dependent, (b) are higher than that obtained for (1S,2R)-PhCH=NCH(Me)CH(OH)Ph (2e), (c) are strongly affected by the nature of the R(1) group, and (d) increase according to the sequence Ph < Fc < 5-MeTf < 3-MeTf.

Quantitative structure-property relationship estimation of cation binding affinity of the common amino acids.

The quantitative structure-property relationship (QSPR) methodology is applied to estimate the binding affinity of lithium, sodium, potassium, copper, and silver cations to the 20 common amino acids. The proposed model, nonlinearly derived from computational neural networks (CNN), contains seven descriptors and was validated by an external prediction set. Good results are obtained with correlation coefficients, R(2), and root-mean-square errors (rms) (kJ/mol) of 0.

A comparison of the binding affinity of the common amino acids with different metal cations.

A theoretical model, based in density functional theory with the B3LYP functional and the DZVP basis set from Salahub, has been applied for the calculation of the binding affinity and cation basicity between the 20 common amino acids and the monovalent cations Li+, Na+, K+, Cu+ and Ag+. These magnitudes have been calculated for every combination of the five cations with the twenty amino acids, thus totalling 100 reactions. The highest binding affinities correspond to copper(I) (302.

Determination of lithium cation basicity from molecular structure.

A quantitative structure-property relationship (QSPR) is developed to calculate the Lithium Cationic Basicity (LCB) of a large set of 229 compounds, of very different chemical nature. The proposed models derived from multiple linear regression analysis (MLRA) and computational neural networks (CNN) contain seven descriptors calculated solely from the molecular structure of compounds. The models were validated by an external prediction set.

Determination of Abraham solute parameters from molecular structure.

The Abraham solute parameters are well-known factors for the quantitative description of solute/solvent interactions. A quantitative structure-property relationship (QSPR) is reported for the E, S, A, and B parameters of a large set of 457 solutes, of very different chemical nature. The proposed models, derived from multilinear regression analysis (MLRA) and computational neural networks (CNN), contain five descriptors calculated solely from the molecular structure of compounds.

A QSPR study of the p solute polarity parameter to estimate retention in HPLC.

A Quantitative Structure-Property Relationship (QSPR) model is developed to calculate the solute polarity parameter p of a set of 233 compounds of a very different chemical nature. The proposed model, derived from multiple linear regression, contains four descriptors calculated from the molecular structure and the well-known hydrophobicity parameter log P(o/w). According to the statistics obtained with the prediction set, the model has a very good prediction capacity (R(2) = 0.

A QSPR study of O-H bond dissociation energy in phenols.

A Quantitative Structure-Property Relationship (QSPR) is developed for the O-H bond dissociation energy (BDE) of a set of 78 phenols. The data set was composed of monosubstituted, disubstituted, and polysubstituted phenolic derivatives containing substituents with different steric and electronic effects in the ortho-, meta-, and para-positions of the aromatic ring. The proposed model, derived from multiple linear regression, contains seven descriptors calculated solely from the molecular structure of compounds.

Polarizabilities of solvents from the chemical composition.

From the experimental polarizability values, alpha, of a large set of solvents containing 426 compounds with very different chemical characteristics, an additive model for the estimation of the polarizability is proposed. The derived average atomic polarizability of 10 elements, C, H, O, N, S, P, F, Cl, Br, and I, allows the calculation of the molecular polarizability of solvents from their chemical composition alone, without any other structural consideration. The average errors are 2.

Synthesis, resolution, and reactivity of benzylmesitylphenylphosphine: a new p-chiral bulky ligand.

The synthesis of P,P'-dimesityl-P,P'-diphenyldiphosphine and benzylmesitylphenylphosphine is described as well as the resolution of the latter ligand by means of homochiral organometallic complexes. The absolute configuration of the phosphine is assigned by NMR spectra, using the homochiral palladacycle as a reference point. The configuration has been confirmed by single crystal X-ray diffraction.