Variable Lipophilicity Research Articles

NIR fluorescent probe with variable lipophilicity for imaging lysosomal copper during cuproptosis in HCC cells

Copper is essential for the activity of vitally important enzymes, while it is toxicity when in excess. Recent research indicates that cells will undergo cuproptosis induced by copper-ionopheres, a kind of copper-dependent programmed death. Cuproptosis shows great potential in counteracting tumor resistance to traditional therapies. Lysosomes should be put more attention, as they are pivot of cellular copper regulation and trafficking. Herein, we developed a novel NIR fluorescent probe, CyCu, to describe lysosomal copper pools during cuproptosis. CyCu shows turn-on response and great selectivity to copper at the maximum emission wavelength of 730 nm. CyCu can accurately target to lysosomes and indicate lysosomal copper pools fluctuation during cuproptosis. The increase of fluorescence intensity of CyCu in glucose-lack HepG2 cells also shows cells preferable to respiration are more sensitive to copper and easier to suffer cuproptosis. So, lysosomal copper, imaged by CyCu, could be a new target of research of HCC (hepatocellular carcinoma) treatment.

Phenolic Compound Composition and Biological Activities of Fractionated Soybean Pod Extract

The objective of this study was to determine the potential of dry extracts from soybean pods as a source of bioactive compounds. The phenolic compound composition of the extract (E) and fraction (F1-F3) as well as their respective lipophilicity were analyzed by UPLC-ESI-QTOF-MS. The biological activity as measured by antioxidant and cytotoxic activity was also evaluated. The in vitro anticancer potential of the ethanolic extract and fraction of soybean pods was measured through MTT assay using human colorectal carcinoma (HTC-116) and prostate cancer (PC-3) cell lines. The F2 fraction, with medium lipophilicity, produced the most pronounced cytotoxic effect in PC-3 cells. Analysis of Pearson’s correlation demonstrated a high relationship between the content of phenolic compounds, the antioxidant activity of the extract and fractions, and cytotoxic activity towards PC-3 cells. UPLC-ESI-QTOF-MS analysis of soybean pod extract resulted in putative identification of 50 polyphenols belonging to three different chemical families (phenolic acids, flavonoids, and other polyphenols), the first time such an analysis has been performed. Among the fractions with variable lipophilicity, fraction F2 was the most abundant in phenolic compounds. This was confirmed in the quantitative analysis, as a result of which the highest total content of phenolic compounds was found in the extract (E) and fraction F2. Soybean pods might be useful material for obtaining preparations with anti-radical and anti-cancer properties. They can also be an active food additive or a component in dietary supplements.

Anticancer Potential and Capsianosides Identification in Lipophilic Fraction of Sweet Pepper (Capsicum annuum L.).

This study aimed to determine the health-promoting properties of sweet pepper by comparing the activity of fractions with variable lipophilicity. Fractions from red pericarp: aqueous (F1), 40% MeOH (F2), and 70% MeOH (F3) were analyzed for antiradical activity (with DPPH• and ABTS+•), and the contents of total phenolic compounds (TP), flavonoids (TF), and dihydroxycinnamic acids (TDHCA). The anticancer potential of the fractions was evaluated in vitro using different cancer cell lines: human colorectal carcinoma (HCT116) and PC-3 (prostate cancer cell). Fibroblast-like cells of L929 obtained from subcutaneous adipose tissue of mouse were used as normal cells. The highest content of TP, TF, and TDHCA along with the strongest antiradical activity was observed for fraction F2, while the strongest anticancer properties against PC-3 were observed in fraction F3. Fraction F3 primarily contained capsianoside derivatives, which had been isolated through chromatographic methods and identified by spectral methods. These analyses helped in identifying 8 compounds, including 3 new compounds.

Bioavailability of microplastic-bound pollutants in vitro: The role of adsorbate lipophilicity and surfactants

The potential role of microplastic particles (MPs) as vectors for lipophilic organic pollutants enhancing their uptake by organisms has repeatedly been discussed in the scientific community. Likewise, several studies indicate an important role of surfactants in pollutant-transfer from MP to organisms. Employing polyethylene particles, the bioavailability of three MP-bound inducers of 7-ethoxyresorufin-O-deethylase (EROD) with variable lipophilicity was quantitatively compared via EROD activity in RTL-W1 cells. In addition, non-cytotoxic surfactant concentrations of Pluronic F-127, rhamnolipids, sodium deoxycholate and sodium dodecyl sulfate (SDS) supplemented to the medium were tested for their effects on pollutant desorption from MPs as well as on cellular EROD induction. Bioavailability of MP-bound pollutants was negatively correlated with lipophilicity, and all surfactants were found to modulate the cellular response towards inducers by unidentified mechanisms. After experimental correction for effects on the cellular response, all surfactants except SDS moderately increased desorption of inducer from MPs. Results on the impact of lipophilicity agree with previously published thermodynamic models, indicating that appreciable pollutant desorption from MPs may only occur for substances with comparatively low lipophilicity, the accumulation of which on MPs is negligible in the environment. However, the role of surfactants should be considered further with respect to potential effects on sorption of pollutants to and from MPs.

NMR Study of Partition and Permeation Properties of Ga(III) Chelates

We found that tris(3-hydroxy-4-pyridinonate) Fe(III) complex [Fe(mpp)3] appears to be a strong candidate for iron fertilizer [1]. Further studies in which three Fe-chelates of the same family of ligands were compared tris(3-hydroxy-4-pyridinonate) Fe(III) complexes [Fe(mpp)3, Fe(dmpp)3 and Fe(etpp)3], were indicative that the first chelate presents a superior ability to be translocated from the roots to the shoots. The three complexes exhibit variable lipophilicity and for that reason will interact differently with membranes. To get insight on the permeation properties of Fe(III)-chelates, we performed NMR studies with parent diamagnetic/isostructural Ga(III)-chelates. The affinity of the complexes for the phospholipid bilayer of POPC/POPE liposomes and permeation properties of the Ga-chelates were estimated on the basis of the induced alterations of a number of NMR parameters, such as chemical shifts, line shape, spin-lattice relaxation time (T1), and translational diffusion coefficient of the lipids and the liposomes. Acknowledgements: This work received financial support from FCT/MEC through national funds and co-financed by FEDER, under the Partnership Agreement PT2020, through the projects UID/QUI/50006/2013-POCI/01/0145/FEDER/007265 (LAQV/REQUIMTE) and project PTDC/AGRPRO/3515/2014-POCI-01-0145-FEDER-016599. [1] Santos, C.S., Carvalho, S.M.P., Leite, A., Moniz, T., Roriz, M., Rangel, A.O.S.S., Rangel, M., Vasconcelos, M.W., Plant Physiology and Biochemistry, 2016, 106, 91-100.

Cut-off effect of radical TEMPO derivatives in olive oil-in-water emulsions.

Three oil-in-water emulsions were prepared from mixtures of olive oil and Tween 20 in water. The effectiveness of a series of radical 2,2,6,6-tetramethylpiperidinoxyl (TEMPO) derivatives of variable lipophilicity in reactions with antioxidant Trolox, and as pyrene-fluorescence quenchers, was compared in the three emulsions. A "cut-off" effect was observed for the pyrene quenching by the probes, but not for their reaction with Trolox. The results were rationalized in terms of the amphiphobic nature of the probes, and the different locations of probe, pyrene and Trolox in the three-phase microheterogeneous systems.

“Cut-off” effect of antioxidants and/or probes of variable lipophilicity in microheterogeneous media

The activities of two hydrophilic (ascorbic acid and Trolox) and two hydrophobic (α-tocopherol and BHT) antioxidants were measured by reaction with a series of 4-alkanoyloxyTEMPO radical probes 1 in buffered (pH 7), aqueous, micellar solutions of reduced Triton-X 100. In all cases, a cut-off effect was observed, in line with previous observations of the same effect for the partitioning of probe series 1 in this medium. These results support an interpretation of the cut-off effect in food emulsions, based on the “amphiphobic” nature of either the antioxidants or probes: competition between two molecular moieties, for the micellar hydrophobic core, tends to expose a reacting fragment differently to a more hydrophilic microenvironment, as the probe or antioxidant hydrophobicity increases.

Zinc oxide nanoparticles with surface modified by degradation of capping polymers in situ during microwave synthesis

Surface modified zinc oxide nanoparticles with variable lipophilicity were prepared by the help of microwave-assisted solvothermal synthesis from mechano-chemically prepared precursor. Sodium carbonate and zinc acetate dihydrate were used as starting materials, diethylene glycol was used as a solvent, poly(ethylene glycol) and polyvinyl alcohol were used as surface capping agents. The zinc oxide was obtained during the first three minutes of reaction and its surface was further modified with prolonged time of the reaction due to degradation of polymers used as capping and stabilising agents. Scanning Electron Microscopy was employed for powder morphology evaluation. Inorganic phase structure development was characterized by means of X-ray diffraction. Nanostructured composite materials with crystallite size below 10nm were obtained with specific surface area varying from 35 to 86m2g−1 according to Brunauer–Emmett–Teller analysis. The progress of degradation of adsorbed polymer moieties was manifested by the powder colour change. Optical properties as well as the structure of materials were further analysed by Diffuse Reflectance Ultraviolet–visible Spectroscopy and Diffuse Reflectance Infrared Fourier Transform Spectroscopy and correlated with Thermogravimetric observations and Lipophilicity degree analysis.

Nanoscale amphiphilic macromolecules with variable lipophilicity and stereochemistry modulate inhibition of oxidized low-density lipoprotein uptake.

Amphiphilic macromolecules (AMs) based on carbohydrate domains functionalized with poly(ethylene glycol) can inhibit the uptake of oxidized low density lipoprotein (oxLDL) and counteract foam cell formation, a key characteristic of early atherogenesis. To investigate the influence of lipophilicity and stereochemistry on the AMs' physicochemical and biological properties, mucic acid-based AMs bearing four aliphatic chains (2a) and tartaric acid-based AMs bearing two (2b and 2l) and four aliphatic chains (2g and 2k) were synthesized and evaluated. Solution aggregation studies suggested that both the number of hydrophobic arms and the length of the hydrophobic domain impact AM micelle sizes, whereas stereochemistry impacts micelle stability. 2l, the meso analogue of 2b, elicited the highest reported oxLDL uptake inhibition values (89%), highlighting the crucial effect of stereochemistry on biological properties. This study suggests that stereochemistry plays a critical role in modulating oxLDL uptake and must be considered when designing biomaterials for potential cardiovascular therapies.

Novel Antimicrobial Peptide Dendrimers with Amphiphilic Surface and Their Interactions with Phospholipids — Insights from Mass Spectrometry

A series of new peptide dendrimers with amphiphilic surface, designed around a dendronized ornithine (Orn) core were synthesized and characterized by ESI-MS, 1H-, 13C- NMR, and CD spectrometry. An improved antimicrobial potency against S. aureus and E. coli was detected as a result of an increased charge, higher branching and variable lipophilicity of the residues located at the C-terminus. Minimal inhibitory concentration (MIC) values indicated that the selected dendrimers were not sensitive to the physiological concentration of Na+ and K+ ions (100 mM), but expressed reduced potency at 10 mM concentration of Mg2+ and Ca2+ ions. Circular dichroism (CD) curves measured under various conditions revealed structure and solvent-dependent curve evolution. ESI-MS studies of gas-phase interactions between selected dendrimers and both anionic (DMPG) and neutral (DMPC) phospholipids revealed the presence of variously charged dendrimer/phospholipid aggregates with 1:1 to 1:5 stoichiometry. The collision-induced fragmentation (CID) of the most abundant [dendrimer/phospholipid]2+ ions of the 1:1 stoichiometry demonstrated that the studied dendrimers formed stronger complexes with anionic DMPG. Both phospholipids have higher affinity towards dendrimers with a more compact structure. Higher differences in CID energy necessary for dissociation of 50% of the complex formed by dendrimers with DMPG vs. DMPC (∆CID50) correlate with a lower hemotoxicity. Mass spectrometry results suggest that for a particular group of compounds the ∆CID50 might be one of the important factors explaining selectivity of antimicrobial peptides and their branched analogs targeting the bacterial membrane. Both circular dichroism and mass spectrometry studies demonstrated that dendrimers of Nα- and Nε-series possess a different conformation in solution and different affinity to model phospholipids, what might influence their specific microbicidal mechanism.

Mono- and dicationic Re(I)/99mTc(I) tricarbonyl complexes for the targeting of energized mitochondria

The enhanced negative mitochondrial membrane potential of tumor cells can increase the cell accumulation of triphenylphosphonium (TPP) derivatives, which prompted us to investigate TPP-containing Re(I)/99mTc organometallic compounds as probes for in vivo targeting of energized mitochondria. Novel compounds (Re1–Re4/Tc1–Tc4) were obtained with bifunctional chelators of the pyrazole-diamine (N,N,N-donors) and pyrazole-aminocarboxylic (N,N,O-donors) type, functionalized with TPP pharmacophores that have been introduced at the central amine of the chelators using different spacers. In this way, dicationic (Re1–Re2, Tc1–Tc2) and monocationic (Re3–Re4, Tc3–Tc4) complexes with variable lipophilicity were synthesized. The 99mTc complexes (Tc1–Tc4) are highly stable under physiological conditions and their chemical identification was done by HPLC comparison with the Re congeners (Re1–Re4), which were fully characterized by common analytical techniques (electrospray ionization mass spectrometry (ESI-MS), IR, multinuclear NMR). The in vitro biological evaluation of Tc1–Tc4 was performed in a panel of human tumor cell lines (PC-3, MCF-7 and H69), including cell lines overexpressing P-glycoprotein (MCF-7/MDR1 and H69/Lx4), and in isolated mitochondria. All the tested complexes showed a low to moderate cellular and mitochondrial uptake and did not undergo significant P-glycoprotein (Pgp)-mediated efflux processes. In particular, the dication Tc2 and the monocation Tc4 presented the highest cellular and mitochondrial uptake. Their cellular uptake was shown to depend on the mitochondrial (Δψm) and plasma membrane (Δψp) potentials. Altogether, the biological properties of these compounds suggest that they might be relevant for the design of radioactive metalloprobes for in vivo targeting of mitochondria.

109Pd labeled 5,10,15,20-tetrakis[4-carboxymethyleneoxyphenyl]porphyrin: a Potential Agent for Targeted Tumor Therapy

Radiolabeled porphyrin derivatives could be envisaged as potential agents for targeted tumor therapy owing to the inherent tumor accumulation property exhibited by porphyrins. However, to achieve adequately high tumor accumulation and retention therein along with fast clearance from all non-target organs, an optimum balance between the hydrophilicity and lipophilicity must be achieved. Based on our prior experiences of working with (109)Pd-labeled porphyrins with variable lipophilicity and hydrophilicity, we have envisioned a suitable porphyrin derivative which could be expected to have the required balance between lipophilicity and hydrophilicity when complexed with (109)Pd. Towards this, 5,10,15,20- tetrakis[4-carboxymethyleneoxyphenyl]porphyrin (PHBEPH) was synthesized, radiolabeled with (109)Pd and its biological behavior in small animal model was studied. The porphyrin derivative was synthesized and characterized following the reported procedure and radiolabeled with (109)Pd [E β(max) = 1.12 MeV, E γ = 88 keV (3.6%), T1/2 = 13.7 h], which was produced by the thermal neutron bombardment on enriched (98% in (108)Pd) metallic Pd target at a flux of 3x1013 n/cm2.s for 3 d. Biological behavior of the radiolabeled agent was studied by biodistribution studies in Swiss mice bearing fibrosarcoma tumors. (109)Pd was produced with a specific activity of ∼1.85 GBq/mg (50 mCi/mg) and radionuclidic purity of 100%. (109)Pd complex of the synthesized porphyrin derivative was prepared with excellent radiochemical purity ( > 98%) and the complex was observed to exhibit Log P value of -1.29. Biodistribution studies revealed good tumor uptake [(3.55±0.49)% injected activity (IA)/g] within 30 min post-injection (p.i.) and retention therein till 24 h [(2.56±0.25)% IA)/g], upto which the study was continued. The complex exhibited fast clearance from the non-target organs with favorable tumor/blood and tumor/muscle ratios [(5.09±0.18)% and (284.44±3.25)% at 24 h p.i.]. The complex exhibited good uptake and retention in the tumor along with encouraging target to non-target ratio. Preliminary biological studies indicated the promising attributes of the agent towards its use for targeted radiotherapy.

Transplantation in Obese Patient

Obesity is a worldwide epidemic leading to severe comorbidity that damages end-organ function. Overall transplant outcomes in this population are inferior to those in nonobese patients. Large population studies show decreased patient and graft survival in obese kidney transplant patients. Despite the poorer outcomes, kidney transplantation is considered because of the survival benefit as compared with the wait-listed dialysis patients. In liver transplantation, the benefit to transplantation as compared with remaining on the list is obvious, as there is no viable liver dialysis at this time. Obesity in potential organ donors impacts both medical and surgical issues. Obesity-related kidney disease affects both the remaining and transplanted kidney. Pancreas donor organs are associated with decreased early graft survival. Liver donor organs with significant steatosis lead to an increased risk for delayed or nonfunction of the organ. Immunosuppressive drugs with variable lipophilicity and altered volume of distribution can greatly affect the therapeutic usefulness of these drugs. Transplant candidates benefit from a multidisciplinary team approach to their care. As the epidemic progresses and less-invasive treatments for metabolic surgery evolve, we are likely to require more patients to lose weight prior to transplantation as we continue to strive for improved outcomes.

Sensing different micellar microenvironments with solvatochromic dyes of variable lipophilicity

The UV/Vis spectral behavior of three solvatochromic N-alkyl α-pyridones of varying lipophilicity was investigated in aqueous solutions of a block copolymer at variable temperatures. The solvatochromic responses of the three analogues to the distinct microenvironments were compared and interpreted in terms of their different location in the microheterogeneous system. The interpretation was supported by 1H NMR measurements and by molecular dynamics simulations that mimicked the interactions of the dyes with the polymeric micelle in water.

Challenges of Abdominal Organ Transplant in Obesity

Obesity is a worldwide epidemic and public health crisis associated with severe comorbidity leading to end organ dysfunction and poorer transplant outcome. Large population studies show decreased patient and graft survival in obese kidney transplant patients. Despite the poorer outcomes, kidney transplant is considered because of the survival benefit as compared to the wait-listed dialysis patients. In liver transplantation, the benefit of transplant as compared to remaining on the list is obvious because there is no viable liver dialysis at this time.Obesity in potential organ donors impacts both medical and surgical issues. Obesity-related kidney disease affects both the remaining and transplanted kidney. Pancreas donor organs are associated with decreased early graft survival. Liver donor organs with significant steatosis lead to an increased risk for delayed function or nonfunction of the organ.Immunosuppressive drugs with variable lipophilicity and altered volume of distribution can greatly affect the therapeutic usefulness of these drugs.Transplant candidates benefit from a multidisciplinary team approach to their care. As the epidemic progresses and less invasive treatments for metabolic surgery evolve, we are likely to see more patients lose weight before transplant as we continue to strive for improved outcomes.

Locus-Specific Microemulsion Catalysts for Sulfur Mustard (HD) Chemical Warfare Agent Decontamination

The rates of catalytic oxidative decontamination of the chemical warfare agent (CWA) sulfur mustard (HD, bis(2-chlororethyl) sulfide) and a range (chloroethyl) sulfide simulants of variable lipophilicity have been examined using a hydrogen peroxide-based microemulsion system. SANS (small-angle neutron scattering), SAXS (small-angle X-ray scattering), PGSE-NMR (pulsed-gradient spin-echo NMR), fluorescence quenching, and electrospray mass spectroscopy (ESI-MS) were implemented to examine the distribution of HD, its simulants, and their oxidation/hydrolysis products in a model oil-in-water microemulsion. These measurements not only present a means of interpreting decontamination rates but also a rationale for the design of oxidation catalysts for these toxic materials. Here we show that by localizing manganese-Schiff base catalysts at the oil droplet-water interface or within the droplet core, a range of (chloroethyl) sulfides, including HD, spanning some 7 orders of octanol-water partition coefficient (K(ow)), may be oxidized with equal efficacy using dilute (5 wt. % of aqueous phase) hydrogen peroxide as a noncorrosive, environmentally benign oxidant (e.g., t(1/2) (HD) approximately 18 s, (2-chloroethyl phenyl sulfide, C(6)H(5)SCH(2)CH(2)Cl) approximately 15 s, (thiodiglycol, S(CH(2)CH(2)OH)(2)) approximately 19 s {20 degrees C}). Our observations demonstrate that by programming catalyst lipophilicity to colocalize catalyst and substrate, the inherent compartmentalization of the microemulsion can be exploited to achieve enhanced rates of reaction or to exert control over product selectivity. A combination of SANS, ESI-MS and fluorescence quenching measurements indicate that the enhanced catalytic activity is due to the locus of the catalyst and not a result of partial hydrolysis of the substrate.

Topography of the active site of the Saccharomyces cerevisiae plasmalemmal dicarboxylate transporter studied using lipophilic derivatives of its substrates

2-Alkylmalonates and O-acyl-L-malates have been found to competitively inhibit the dicarboxylate transporter of Saccharomyces cerevisiae cells, and the substrate derivatives chosen did not penetrate across the plasmalemma under the experiment conditions. Probing of the active site of this transporter has revealed a large lipophilic area stretching between the 0.72 to 2.5 nm from the substrate-binding site. Itaconate inhibited the transport fivefold more effectively than L-malate. This suggests the existence of a hydrophobic region immediately near the dicarboxylate-binding site (to 0.72 nm). The yeast plasmalemmal transporter was different from the rat liver mitochondrial dicarboxylate transporter. An area with variable lipophilicity adjoining the substrate-binding site has been revealed in the latter by a similar method. This area is mainly hydrophobic at distances up to 1.76 nm from the binding site and is separated by a hydrophilic region from 0.38 to 0.88 nm. Fumarate but not maleate competitively inhibited succinate transport into the S. cerevisiae cells. It is suggested that the plasmalemmal transporter binds the substrate in the trans-conformation. The prospects of the proposed approach for scanning lipophilic profiles of channels of different transporters are discussed.

Synthesis and Cytotoxic Activity of Polyamine Analogues of Camptothecin

A number of derivatives of camptothecin with a polyamine chain linked to position 7 of camptothecin via an amino, imino, or oxyiminomethyl group were synthesized and tested for their biological activity. All compounds showed marked growth inhibitory activity against the H460 human lung carcinoma cell line. In particular, the iminomethyl derivatives where the amino groups of the chain were protected with Boc groups exhibited a high potency, with IC50 values of approximately 10(-8) M. The pattern of DNA cleavage in vitro and the persistence of the cleavable ternary complex drug-DNA-topoisomerase I observed with polyamine conjugates containing free amino groups support a contribution of specific drug interaction with DNA as a determinant of activity. Modeling of compound 7c in the complex with topoisomerase 1 and DNA is consistent with this hypothesis. The lack of a specific correlation between stabilization of the cleavable complex and growth inhibition likely reflects multiple factors including the cellular pharmacokinetic behavior related to the variable lipophilicity of the conjugate, and the nature and linkage of the polyamine moiety.

Study of active site topography of rat liver mitochondrial dicarboxylate transporter using lipophilic substrate derivatives

Earlier it has been demonstrated that the active site (substrate-binding site + active site channel) of rat liver mitochondrial dicarboxylate transporter is characterized by rather complex topography. Probing the active site with 2-monoalkylmalonates revealed the existence of internal and external lipophilic areas separated by a polar region. A two substrate-binding site model of the transporter has been supposed. The correctness of this model has been evaluated by probing the active site with O-acyl-L-malates differing from 2-monoalkylmalonates by 0.23 nm longer distance from the anion groups to the aliphatic chain. Changes in the polar group of the probe did not prevent its binding and showed the same variable lipophilicity pattern for the transporter channel. Probing with alpha,omega-alkylene dimalonates did not reveal the second substrate-binding site at the active site. The substrate-binding site did not show any differences in affinity to O-acyl-derivatives of L-malate and D-malate, except L-malate binds more effectively than D-malate. This suggests involvement of the L-malate hydroxyl group in substrate binding and stereospecific behavior of the transporter substrate-binding site. A modified one substrate-binding site model of the dicarboxylate transporter is discussed.

New lipophilic 3-hydroxy-4-pyridinonate iron(iii) complexes: synthesis and EXAFS structural characterisation

New tris-iron(III) chelates of 3-hydroxy-4-pyridinone ligands derived from maltol (3-hydroxy-2-methyl-4-pyrone) or ethylmaltol (2-ethyl-3-hydroxy-4-pyrone), including a variety of N-aryl (phenyl, 4'-tolyl, 4'-(n-butyl)phenyl, 4'-(n-hexyl)phenyl) and N-benzyl (4'-methylbenzyl, 4'-fluorobenzyl and 4'-(trifluoromethyl)benzylamine) substituents on the nitrogen atom of the pyridinone ring, have been prepared. Characterization by C,H,N elemental analysis and thermogravimetric measurements indicates that most of the complexes are obtained as hydrates of general formula ML3.xH2O. Structural characterization of these difficult to crystallize lipophilic complexes has been achieved by EXAFS spectroscopy. Solutions of iron(III) complexes of maltol, ethylmaltol, 1,2-dimethyl-3-hydroxy-4-pyridinone and 1-phenyl-2-methyl-3-hydroxy-4-pyridinone in methanol-water mixtures were also examined by EXAFS. Distances from the central atom to ligand atoms, within 6 A of the metal, have been determined in the solid and solution samples and the results show that the structure observed in the powder is maintained in solution. The local structure around the metal centre, bond distances and bond angles, does not change significantly with variable lipophilicity, thus indicating that ligands may be tailored according to specific needs without altering their chelation properties. EXAFS data analysis for this set of tris-iron(III) compounds illustrates the important contribution of both intra-ligand and inter-ligand multiple scattering pathways through the metal centre to a peak observed in the FT spectrum at twice the metal ligand distance (approximately 4 A). The present results demonstrate that EXAFS features at twice the metal-ligand distance are valuable in the assignment of molecular geometry and that location of hydration water molecules, by EXAFS analysis, is limited by the geometry of the complexes, in particular for those in which ligands containing phenyl rings are present.