Unsubstituted Parent Research Articles

The crystal structure and thermal expansion of novel substitutionally disordered Ca10TM0.5(VO4)7 (TM = Co, Cu) orthovanadates.

The whitlockite-related materials have attracted researchers' attention because of their potential application in various fields, especially in optoelectronics. In the present work, the structure of novel whitlockite-related oxides Ca10TM0.5(VO4)7 (TM = Co, Cu) is studied at room and high temperatures, using X-ray powder diffraction. These compounds form by fractional substitution of divalent transition metal atoms into the Ca3(VO4)2 lattice. Rietveld refinements provided the structural details. The lattice parameters are a = 10.78074(6) Å, c = 37.8196(2) Å, and V = 3806.67(4) Å3 for Ca10Co0.5(VO4)7 and a = 10.78710(7) Å, c = 37.8997(3) Å, and V = 3819.23(4) Å3 for Ca10Cu0.5(VO4)7. Structure refinement results show that among the five available sites (M1-M5), the M2+ ions select the M5 site. This finding is confirmed by analysis of interatomic distances: due to the difference in size between TM and Ca ions sharing the M5 site, the M5-O distance shortens by about 5.0% for Ca10Co0.5(VO4)7 and 2.7% for Ca10Cu0.5(VO4)7 with respect to the unsubstituted parent compound, Ca3(VO4)2. The observed trends in the crystallographic properties of the studied crystals are in line with those of previously reported structurally related phosphates, Ca10.5-xMx(PO4)7 (M = Mg or divalent transition metal). Moreover, the observed tendency for occupation of M5 by small divalent ions follows the earlier theoretical results. For cobalt and copper substituted orthovanadate and orthophosphate whitlockite related materials, a linear variation in the unit cell size is demonstrated. The common equation for evaluation of volume is applicable to the substitution of the two transition metals in orthovanadate and orthophosphate whitlockite related materials. Thermal expansion is investigated for both compounds. The variations of the lattice parameters and the thermal expansion coefficient with temperature are determined in the 300-810 K range. The lattice parameter, a, expands by 0.80% for Ca10Co0.5(VO4)7 and 0.74% for Ca10Cu0.5(VO4)7 in this range. The lattice parameter, c, enlarges by about 0.70% for both samples. In the studied temperature range, the volume thermal expansion coefficient of Ca10Co0.5(VO4)7 increases from 37.2 to 44.8 MK-1 and for Ca10Cu0.5(VO4)7, it increases from 35.1 to 45.2 MK-1; the observed expansion anisotropy is smaller than those of other related compounds.

Photophysical Properties of Fluorescent 2-(Phenylamino)-1,10-phenanthroline Derivatives†.

The present study details the experimental and theoretical characterization of the photophysical properties of 14 examples of 2-(phenylamino)-1,10-phenanthrolines (1). The absorption spectra of 1 are substituent-dependent but in a general manner present absorption bands at wavelengths of ~230; ~300; ~335 and a shoulder at ~380nm. Electron-donating groups (EDG) and electron-withdrawing groups (EWG), respectively, result in bathochromic and hypsochromic shifts. Compounds 1 are highly luminescent, in contrast to phenanthroline, and emit in the region between 350 and 500nm with substituent-dependent λmax emission. The emission spectra show a redshift for EDG (4-OMe 62nm; 4-Me 19nm) and a blueshift for EWG (4-CN 41nm; 4-CF3 38nm) relative to the emission of the unsubstituted parent compound 1a. Plotting the against Hammett σ+ constants gave an excellent linear correlation demonstrating the electron-deficient nature of the excited state and how the substituents (de)stabilize S1 . Theoretical calculations revealed a HOMO-LUMO π-π* electronic transition to S1 which in combination with difference (S1 -S0 ) in electron density maps revealed charge-transfer character. Strongly electron-withdrawing substituents switch off the charge transfer to give rise to a local excitation.

Comparison of the effect of N-methyl and N-aryl groups on the hydrolytic stability and electronic properties of betalain dyes

Betalains are antioxidant secondary metabolites that emerged as safe color additives for food and cosmetics, fluorescent dyes, and redox mediators. Herein, we describe the semisynthesis of N-methyl phenylbetalain (mepBeets) and N-aryl phenylbetalain (dipBeets) dyes and compare the effect of the structure on their hydrolytic stability and electronic properties. Eight model compounds were semisynthesized by coupling betalamic acid with either N-methyl anilines or N-aryl anilines in ethyl acetate using p-toluenesulfonic acid as catalyst. The presence of electron-withdrawing substituents in the aryl moiety of mepBeets and dipBeets results in faster hydrolysis, lower anodic potentials and increased fluorescence quantum yields compared to the corresponding unsubstituted parent compounds. The results are rationalized by considering the charge distribution in the 1,7-diazaheptamethinium chromophore and are useful for the development of new hydrolytically stable betalain dyes with tunable redox and optical properties.

Density Functional Theory Calculation on the Structural, Electronic, and Optical Properties of Fluorene-Based Azo Compounds.

In the present work, a theoretical study was carried out to study the molecular structure, harmonic vibrational frequencies, normal force field calculations, and Raman scattering activities for fluorene π-conjugation spacer containing azo-based dye named trans- and cis-bis(9H-fluoren-2-yl)diazene (AzoFL) at density functional theory using B3LYP (Becke-3–Lee–Yang–Parr) functional and 6-31+G(d,p) basis set. The theoretical calculations have also been performed with fluorene and the trans- and cis-isomers of diazene, difluorodiazene by the same method DFT-B3LYP/6-31+G(d,p) and basis set. The present DFT calculation shows that the trans-AzoFL is more stable than the cis-AzoFL by 16.33 kcal/mol. We also report the results of new assignments of vibrational frequencies obtained on the basis of the present calculations. Time-dependent DFT (TD-DFT) and ZIndo calculations have been performed to study the UV–vis absorption behavior and frontier molecular orbitals for the above-mentioned compounds. The UV–vis spectrum from TD-DFT calculation shows the π–π* transition bands at λmax 423.53 nm (εmax 6.0 × 104 M–1 cm–1) and at λmax 359.45 nm (εmax 1.7 × 104 M–1 cm–1), respectively, for trans- and cis-AzoFL. Compared to parent trans-diazene (λmax 178.97 nm), a significant variation to longer wavelength (∼245 nm) is observed due to the incorporation of the fluorene (FL) ring into the −N=N– backbone. The co-planarity of the two FL rings with the longer N=N bond length compared to the unsubstituted parent diazene indicates the effective red shift due to the extended π-conjugation in trans-AzoFL. The nonplanarity of cis-AzoFL (48.1° tilted about the C–N bond relative to the planar N=N–C bond) reflects its ∼64 nm blue shift compared to that of trans-counterpart.

Structure\u2013activity relationships in a series of antiplasmodial thieno[2,3-b]pyridines

BackgroundMalaria is one of the most prevalent tropical infectious diseases. Since recently cases of artemisinin resistance were reported, novel anti-malarial drugs are required which differ from artemisinins in structure and biological target. The plasmodial glycogen synthase kinase-3 (PfGSK-3) was suggested as a new anti-malarial drug target. 4-Phenylthieno[2,3-b]pyridines were previously identified as selective PfGSK-3 inhibitors with antiplasmodial activity. The present study aims at identifying a molecular position on this scaffold for the attachment of side chains in order to improve solubility and antiplasmodial activity. Furthermore, the role of axial chirality in the compound class for antiplasmodial activity and PfGSK-3 inhibition was investigated.Methods4-Phenylthieno[2,3-b]pyridines with substituents in 4-position of the phenyl ring were docked into the ATP binding site of PfGSK-3. The compounds were synthesized employing a Thorpe reaction as final step. The enantiomers of one congener were separated by chiral HPLC. All derivatives were tested for inhibition of asexual erythrocytic stages of transgenic NF54-luc Plasmodium falciparum. Selected compounds with promising antiplasmodial activity were further evaluated for inhibition of HEK293 cells as well as inhibition of isolated PfGSK-3 and HsGSK-3. The kinetic aqueous solubility was assessed by laser nephelometry.ResultsThe para position at the 4-phenyl ring of the title compounds was identified as a suitable point for the attachment of side chains. While alkoxy substituents in this position led to decreased antiplasmodial activity, alkylamino groups retained antiparasitic potency. The most promising of these congeners (4h) was investigated in detail. This compound is a selective PfGSK-3 inhibitor (versus the human GSK-3 orthologue), and exhibits improved antiplasmodial activity in vitro as well as better solubility in aqueous media than its unsubstituted parent structure. The derivative 4b was separated into the atropisomers, and it was shown that the (+)-enantiomer acts as eutomer.ConclusionsThe attachment of alkylamino side chains leads to the improvement of antiplasmodial activity and aqueous solubility of selective PfGSK-inhibitors belonging to the class of 4-phenylthieno[2,3-b]pyridines. These molecules show axial chirality, a feature of high impact for biological activity. The findings can be exploited for the development of improved selective PfGSK-3 inhibitors.

Defect structure in δ-Bi5PbY2O11.5.

A detailed study of the defect structure in a di-substituted δ-Bi2O3 type phase, δ-Bi5PbY2O11.5, is presented. Using a combination of conventional Rietveld analysis of neutron diffraction data, reverse Monte Carlo (RMC) analysis of total neutron scattering data and ab initio molecular dynamics (MD) simulations, both average and local structures have been characterized. δ-Bi5PbY2O11.5 represents a model system for the highly conducting δ-Bi2O3 type phases, in which there is a higher nominal vacancy concentration than in the unsubstituted parent compound. Uniquely, the methodology developed in this study has afforded the opportunity to study both oxide-ion vacancy ordering as well as specific cation–cation interactions. Oxide-ion vacancies in this system have been found to show a preference for association with Pb2+ cations, with some evidence for clustering of these cations. The system shows a non-random distribution of vacancy pair alignments, with a preference for 〈100〉 ordering, the extent of which shows thermal variation. MD simulations indicate a predominance of oxide-ion jumps in the 〈100〉 direction.

Phase transitions in tantalum-modified silver niobate ceramics for high power energy storage

Ag(Nb0.8Ta0.2)O3 is used here as a model system to shed light on the nature of the low temperature phase behavior of the unsubstituted parent compound AgNbO3, which is an important material for high-power energy storage applications.

Toxicokinetics and bioaccumulation of polycyclic aromatic compounds in wood frog tadpoles (Lithobates sylvaticus) exposed to Athabasca oil sands sediment

We performed accumulation-elimination experiments of polycyclic aromatic compounds (PACs) in wood frog tadpoles (Lithobates sylvaticus) using river sediment from Canada’s Athabasca oil sands region. The PACs in wood frog tadpoles were ∼2x higher on average when the animals were in direct contact with PAC-contaminated sediment than when they were separated from the sediment with a screen and exposed only to aqueous PACs. These results suggest that sediment exposure/ingestion contributes as much to PAC accumulation in tadpoles as exposure via aqueous pathways. Alkyl-substituted PAC concentrations in exposed tadpoles exceeded those of the unsubstituted (parent) PACs by about 10 × . Bioaccumulation factors ranged between 0.01 and 4.93, with parent PACs having higher bioaccumulation factors than alkylated PACs. Wood frog tadpoles efficiently eliminated and metabolized most parent and alkyl-substituted PACs, though some compounds (e.g., C4-naphthalenes) had higher bioaccumulation potential and may serve as effective markers of exposure. Here we present a comprehensive analysis of the toxicokinetics and bioaccumulation of PACs (52 analytes) in amphibian larvae, and highlight the importance of sediment exposure when considering the bioaccumulation and potential biological impact of PACs in benthic and epibenthic organisms.

Photo-Induced Charge Separation vs. Degradation of a BODIPY-Based Photosensitizer Assessed by TDDFT and RASPT2

A meso-mesityl-2,6-iodine substituted boron dipyrromethene (BODIPY) dye is investigated using a suite of computational methods addressing its functionality as photosensitizer, i.e., in the scope of light-driven hydrogen evolution in a two-component approach. Earlier reports on the performance of the present iodinated BODIPY dye proposed a significantly improved catalytic turn-over compared to its unsubstituted parent compound based on the population of long-lived charge-separated triplet states, accessible due to an enhanced spin-orbit coupling (SOC) introduced by the iodine atoms. The present quantum chemical study aims at elucidating the mechanisms of both the higher catalytic performance and the degradation pathways. Time-dependent density functional theory (TDDFT) and multi-state restricted active space perturbation theory through second-order (MS-RASPT2) simulations allowed identifying excited-state channels correlated to iodine dissociation. No evidence for an improved catalytic activity via enhanced SOCs among the low-lying states could be determined. However, the computational analysis reveals that the activation of the dye proceeds via pathways of the (prior chemically) singly-reduced species, featuring a pronounced stabilization of charge-separated species, while low barriers for carbon-iodine bond breaking determine the photostability of the BODIPY dye.

Synthesis of an anionic derivative of the terpyridine ligand

A procedure for preparing a 4′-triphenylborate-substituted derivative of the 2,2′:6′,2″-terpyridine ligand is described. Such a modification renders the terpyridine ligand anionic, which enables unique design possibilities for coordination chemistries involving metal ions relative to the unsubstituted parent ligand. Proof-in-principle that this new ligand can coordinate to transition metals was provided through the synthesis of a novel nickel complex.

Cross-Coupling Approach to an Array of Macrocyclic Receptors Functioning as Chiral Solvating Agents.

Chiral macrocyclic receptors 1 with multiple hydrogen-bonding sites in the cavity were synthesized and used as NMR chiral solvating agents (CSAs). The Suzuki-Miyaura cross-coupling reaction gave rapid access to a series of variants 1b-p of unsubstituted parent compound 1a. Among them, 1d with the 4-cyanophenyl group at the 3,3'-positions of the binaphthyl moiety was the most excellent CSA for a benchmark analyte compound, 2-chloropropionic acid (CPA); both of the quartet and doublet signals of CPA were split most completely in CDCl3. Binding constants ( Ka) determined in CDCl3 by NMR titrations indicated that ( R)-1d was the most enantioselective ( Ka( S)/ Ka( R) = 5.4). Interestingly, the Ka value of ( R)-1d for ( S)-CPA (5900) was greater than that of ( R)-1a for ( S)-CPA (3080), which strongly suggests an attractive interaction between the 4-cyanophenyl group of ( R)-1d and ( S)-CPA. The X-ray crystal structure of 1d indicates that one of the two H atoms meta to the cyano group is directed toward the cavity. DFT calculations suggested that this H atom of the 4-cyanophenyl group of ( R)-1d forms a weak hydrogen bond with the Cl atom of ( S)-CPA (C-H···Cl-C hydrogen bond).

Synthesis, spectroscopy and singlet oxygen quantum yield of a non-aggregating hexadecamethyl-substituted phthalocyanine silicon(IV) derivative

A rigid hexadecamethyl substituted phthalocyanine (Pc*) silicon(IV) dichloride was synthesized by template cyclization of corresponding 1,3-diiminoisoindoline derivative with SiCl4. Attempts to prepare the same compound by insertion of HSiCl3 into preformed H2Pc* in the presence of bases were unsuccessful. Exchange of the axial chloride ligands with trimethylsiloxy groups made the molecular complex Pc*Si(OTMS)2 very soluble and non-aggregating, as shown by UV–Vis experiments. The effect of such peripheral alkyl substitution on the singlet oxygen quantum yield of the Pc*Si(OTMS)2 complex was determined and found to be 0.28; significantly lower than that for unsubstituted parent PcSi(OTMS)2. The merit of improving solubility over reduced singlet oxygen quantum yields is discussed.

Tacripyrimidines, the first tacrine-dihydropyrimidine hybrids, as multi-target-directed ligands for Alzheimer's disease

Notwithstanding the combination of cholinesterase (ChE) inhibition and calcium channel blockade within a multitarget therapeutic approach is envisaged as potentially beneficial to confront Alzheimer's disease (AD), this strategy has been scarcely investigated. To explore this promising line, a series of 5-amino-4-aryl-3,4,6,7,8,9-hexahydropyrimido [4,5-b]quinoline-2(1H)-thiones (tacripyrimidines) (4a-l) were designed by juxtaposition of tacrine, a ChE inhibitor (ChEI), and 3,4-dihydropyrimidin-2(1H)-thiones, as efficient calcium channel blockers (CCBs). In agreement with their design, all tacripyrimidines, except the unsubstituted parent compound and its p-methoxy derivative, acted as moderate to potent CCBs with activities generally similar or higher than the reference CCB drug nimodipine and were modest-to-good ChEIs. Most interestingly, the 3′-methoxy derivative (4e) emerged as the first well balanced ChEI/CCB agent, acting as low micromolar hChEI (3.05 μM and 3.19 μM on hAChE and hBuChE, respectively) and moderate CCB (30.4% at 1 μM) with no significant hepatotoxicity toward HepG2 cells and good predicted oral absorption and blood brain barrier permeability.

Tris[2,2,6,6-tetra-methyl-8-(tri-methyl-sil-yl)benzo[1,2-d;4,5-d']bis-(1,3-di-thiol)-4-yl]methanol diethyl ether monosolvate.

The title compound, a tri-aryl-methanol, C46H64OS12Si31, was synthesized via li-thia-tion of tris-2,2,6,6-tetra-methyl-benzo[1,2-d;4,5-d']bis-[1,3]di-thiol-4-yl-methanol, 2, and electrophilic quenching with tri-methyl-silyl chloride. The current crystal structure reveals information about the reactivity of this compound and compares well with the structure reported for the unsubstituted parent compound 2 [Driesschaert et al. (2012 ▸). Eur. J. Org. Chem.33, 6517-6525]. The title compound 1 forms mol-ecular propellers and crystallizes in P [Formula: see text], featuring an unusually long Si-Car bond of 1.910 (3) Å. Moreover, the geometry at the central quaternary carbon is rather trigonal-pyramidal than tetra-hedral due to vast intra-molecular stress. One tri-methyl-silyl group is disordered over two positions in a 0.504 (4):0.496 (4) ratio and one S atom is disordered over two positions in a 0.509 (7):0.491 (7) ratio. The contribution of disordered diethyl ether solvent mol-ecule(s) was removed using the PLATON SQUEEZE (Spek, 2015 ▸) solvent masking procedure. These solvent mol-ecules are not considered in the given chemical formula and other crystal data.

Crystal structure of (1S,4S)-2,5-diazo-niabi-cyclo[2.2.1]heptane dibromide.

The cage of 2,5-di-aza-bicyclo-[2.2.1]heptane is frequently employed in synthetic chemistry as a rigid bicyclic counterpart of the piperazine ring. The 2,5-di-azabicyclo-[2.2.1]heptane scaffold is incorporated into a variety of compounds having pharmacological and catalytic applications. The unsubstituted parent ring of the system, 2,5-di-aza-bicyclo-[2.2.1]heptane itself, has not been structurally characterized. We herein report on the mol-ecular structure of the parent ring in (1S,4S)-2,5-diazo-niabi-cyclo-[2.2.1]heptane dibromide, C5H12N22+·2Br-. The asymmetric unit contains two crystallographically independent cages of 2,5-di-aza-bicyclo-[2.2.1]heptane. Each cage is protonated at the two nitro-gen sites. The overall charge balance is maintained by four crystallographically independent bromide ions. In the crystal, the components of the structure are linked via a complex three-dimensional network of N-H⋯Br hydrogen bonds.

Study on the Alkylation Reactions of N(7)-Unsubstituted 1,3-Diazaoxindoles.

The chemistry of the 5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one (1,3-diazaoxindole) compound family, possessing a drug-like scaffold, is unexplored. In this study, the alkylation reactions of N(7)-unsubstituted 5-isopropyl-1,3-diazaoxindoles bearing various substituents at the C(2) position have been investigated. The starting compounds were synthesized from the C(5)-unsubstituted parent compounds by condensation with acetone and subsequent catalytic reduction of the 5-isopropylidene moiety. Alkylation of the thus obtained 5-isopropyl derivatives with methyl iodide or benzyl bromide in the presence of a large excess of sodium hydroxide led to 5,7-disubstituted derivatives. Use of butyllithium as the base rendered alkylation in the C(5) position possible with reasonable selectivity, without affecting the N(7) atom. During the study on the alkylation reactions, some interesting by-products were also isolated and characterized.

Organic Phosphorescence Nanowire Lasers.

Organic solid-state lasers (OSSLs) based on singlet fluorescence have merited intensive study as an important class of light sources. Although the use of triplet phosphors has led to 100% internal quantum efficiency in organic light-emitting diodes (OLEDs), stumbling blocks in triplet lasing include generally forbidden intersystem crossing (ISC) and a low quantum yield of phosphorescence (ΦP). Here, we reported the first triplet-phosphorescence OSSL from a nanowire microcavity of a sulfide-substituted difluoroboron compound. As compared with the unsubstituted parent compound, the lone pair of electrons of sulfur substitution plus the intramolecular charge transfer interaction introduced by the nitro moiety lead to an highly efficient T1 (π,π*) ← S1 (n,π*) ISC (ΦISC = 100%) and a moderate ΦP (10%). This, plus the optical feedback provided by nanowire Fabry-Perot microcavity, enables triplet-phosphorescence OSSL emission at 650 nm under pulsed excitation. Our results open the door for a whole new class of laser materials based on previously untapped triplet phosphors.

Novel 5-substituted 3-hydroxyphenyl and 3-nitrophenyl ethers of S-prolinol as α4β2-nicotinic acetylcholine receptor ligands

A series of 3-nitrophenyl and 3-hydroxyphenyl ethers of (S)-N-methylprolinol bearing bulky and lipophilic substituents at phenyl C5 were tested for affinity at α4β2 and α3β4 nAChRs. The two phenyl ethers 5-substituted with 6-hydroxy-1-hexynyl showed high α4β2 affinity and significantly increased α4β2/α3β4 selectivity compared to the respective unsubstituted parent compounds. Within the two series of novel phenyl ethers, we observed parallel shifts in affinity and, furthermore, the increase in α4β2/α3β4 selectivity resulting from the hydroxyalkynyl substitution parallels that reported for the same modification at the 3-pyridyl ether of (S)-N-methylprolinol (A-84543), a well-known potent α4β2 agonist. On the basis of these results, our nitrophenyl and hydroxyphenyl prolinol ethers can be considered bioisosteres of the pyridyl ether A-84543 and lead compounds candidable to analogous optimization processes.

On the ultrafast photo-induced dynamics of α-terpinene.

The ultrafast relaxation pathway of α-terpinene was studied by photoionization-photoelectron spectroscopy for a range of excitation conditions. Time-resolved spectra were obtained upon optical excitation with ultrashort laser pulses at 5.56 eV, 4.96 eV, 4.76 eV, and 4.56 eV, followed by ionization with 3.06 eV pulses. The experiments yielded spectra of the initially excited state, which decays with a time constant of 66 fs, independent of the excitation wavelength. We also observed a sequential series of Rydberg peaks, including the s, p, and d states with n = 3-6, which capture the travel times on the ensuing reaction path. There is no statistically significant dependence of the travel time on the excitation energy. A comparison of the time-dependent signals with those of the un-substituted parent molecule, 1,3-cyclohexadiene, shows that the substituents on α-terpinene slow the reaction down by a factor of about 2.

CF3 Derivatives of the Anticancer Ru(III) Complexes KP1019, NKP-1339, and Their Imidazole and Pyridine Analogues Show Enhanced Lipophilicity, Albumin Interactions, and Cytotoxicity

The Ru(III) complexes indazolium [trans-RuCl4(1H-indazole)2] (KP1019) and sodium [trans-RuCl4(1H-indazole)2] (NKP-1339) are leading candidates for the next generation of metal-based chemotherapeutics. Trifluoromethyl derivatives of these compounds and their imidazole and pyridine analogues were synthesized to probe the effect of ligand lipophilicity on the pharmacological properties of these types of complexes. Addition of CF3 groups also provided a spectroscopic handle for (19)F NMR studies of ligand exchange processes and protein interactions. The lipophilicities of the CF3-functionalized compounds and their unsubstituted parent complexes were quantified by the shake-flask method to give the distribution coefficient D at pH 7.4 (log D7.4). The solution behavior of the CF3-functionalized complexes was characterized in phosphate-buffered saline (PBS) using (19)F NMR, electron paramagnetic resonance (EPR), and UV-vis spectroscopies. These techniques, along with fluorescence competition experiments, were also used to characterize interactions with human serum albumin (HSA). From these studies it was determined that increased lipophilicity correlates with reduced solubility in PBS but enhancement of noncoordinate interactions with hydrophobic domains of HSA. These protein interactions improve the solubility of the complexes and inhibit the formation of oligomeric species. EPR measurements also demonstrated the formation of HSA-coordinated species with longer incubation. (19)F NMR spectra show that the trifluoromethyl complexes release axial ligands in PBS and in the presence of HSA. In vitro testing showed that the most lipophilic complexes had the greatest cytotoxic activity. Addition of CF3 groups enhances the activity of the indazole complex against A549 nonsmall cell lung carcinoma cells. Furthermore, in the case of the pyridine complexes, the parent compound was inactive against the HT-29 human colon carcinoma cell line but showed strong cytotoxicity with CF3 functionalization. Overall, these studies demonstrate that lipophilicity may be a determining factor in the anticancer activity and pharmacological behavior of these types of Ru(III) complexes.