Novel diaroylhydrazine ligands as iron chelators: coordination chemistry and biological activity

The search for orally effective drugs for the treatment of iron overload disorders is an important goal in improving the health of patients suffering diseases such as beta-thalassemia major. Herein, we report the syntheses and characterization of some new members of a series of N-aroyl-N'-picolinoyl hydrazine chelators (the H2IPH analogs). Both 1:1 and 1:2 Fe-III:L complexes were isolated and the crystal structures of Fe(HPPH)Cl-2, Fe(4BBPH)Cl-2, Fe(HAPH)(APH) and Fe(H3BBPH)(3BBPH) were determined (H2PPH=N,N'-bis-picolinoyl hydrazine; H(2)APH=N-4-aminobenzoyl-N'-picolinoyl hydrazine, H(2)3BBPH=N-3-bromobenzoyl-N'-picolinoylhydrazine and H(2)4BBPH=N-(4-bromobenzoyl)-N'-(picolinoyl)hydrazine). In each case, a tridentate N,N,O coordination mode of each chelator with Fe was observed. The Fe-III complexes of these ligands have been synthesized and their structural, spectroscopic and electrochemical characterization are reported. Five of these new chelators, namely H2BPH (N-(benzoyl)-N'-(picolinoyl)hydrazine), H2TPH (N-(2-thienyl)-N'-(picolinoyl)-hydrazine), H2PPH, H(2)3BBPH and H(2)4BBPH, showed high efficacy at mobilizing Fe-59 from cells and inhibiting Fe-59 uptake from the serum Fe transport protein, transferrin (Tf). Indeed, their activity was much greater than that found for the chelator in current clinical use, desferrioxamine (DFO), and similar to that observed for the orally active chelator, pyridoxal isonicotinoyl hydrazone (H2PIH). The ability of the chelators to inhibit Fe-59 uptake could not be accounted for by direct chelation of Fe-59-Tf. The most effective chelators also showed low antiproliferative activity which was similar to or less than that observed with DFO, which is important in terms of their potential use as agents to treat Fe-overload disease.

Oxidation of low density lipoprotein by iron at lysosomal pH: implications for atherosclerosis

Low density lipoprotein (LDL) has recently been shown to be oxidised by iron within the lysosomes of macrophages and this is a novel potential mechanism for LDL oxidation in atherosclerosis. Our aim was to characterise the chemical and physical changes induced in LDL by iron at lysosomal pH and to investigate the effects of iron chelators and α-tocopherol on this process. LDL was oxidised by iron at pH 4.5 and 37°C and its oxidation monitored by spectrophotometry and HPLC. LDL was oxidised effectively by FeSO4 (5-50 µM) and became highly aggregated at pH 4.5, but not at pH 7.4. Cholesteryl esters decreased and after a pronounced lag 7-ketocholesterol increased greatly. Total hydroperoxides (measured by tri-iodide assay) increased up to 24 h and then decreased only slowly. The lipid composition after 12 h at pH 4.5 and 37°C was similar to that of LDL oxidised by copper at pH 7.4 and 4°C, i.e. rich in hydroperoxides but low in oxysterols. Previously oxidised LDL aggregated rapidly and spontaneously at pH 4.5, but not at pH 7.4. Ferrous was much more effective than ferric iron at oxidising LDL when added after the oxidation was already underway. The iron chelators diethylenetriaminepentaacetic acid and, to a lesser extent, desferrioxamine inhibited LDL oxidation when added during its initial stages, but were unable to prevent LDL aggregating after it had been partially oxidised. Surprisingly, desferrioxamine increased the rate of LDL modification when added late in the oxidation process. α-Tocopherol enrichment of LDL initially increased the oxidation of LDL, but inhibited it later. The presence of oxidised and highly aggregated lipid within lysosomes has the potential to perturb the function of these organelles and to promote atherosclerosis.

Iron analysis in bottle profiles off Mauritania

Iron solubility measurements in the Mauritanian upwelling and the adjacent Open Ocean of the Tropical Atlantic show for all stations lower values in the surface mixed layer than at depth below the pycnocline. We attribute this distribution to a combination of loss terms, chiefly photo-oxidation of organic ligands in the surface, and supply terms, predominantly from the release of ligands from the decomposition of organic matter. Significant correlations with pH, oxygen and phosphate for all samples below the surface mixed layer indicate that biogenic remineralisation of organic matter results in the release of iron binding ligands into the dissolved phase. The comparison of the cFeS/PO4**3- ratio with other published data from intermediate and deep waters in the Pacific suggests an enhanced release of iron chelators in the more productive Mauritanian upwelling zone.

Modeling iron-catecholates binding to NGAL protein

Neutrophil gelatinase associated lipocalin (NGAL) protein is attracting a great interest because of its antibacterial properties played upon modulating iron content in competition against iron acquisition processes developed by pathogenic bacteria that bind selective ferric iron chelators (siderophores). Besides its known high affinity to enterobactin, the most important siderophore, it has been recently shown that NGAL is able to bind Fe(III) coordinated by catechols. The selective binding of Fe(III)-catechol ligands to NGAL is here studied by using iron coordination structures with one, two, and three catecholate ligands. By means of a computational approach that consists of B3LYP/6-311G(d,p) quantum calculations for geometries, electron properties and electrostatic potentials of ligands, protein–ligand flexible docking calculations, analyses of protein–ligand interfaces, and Poisson–Boltzmann electrostatic potentials for proteins, we study the binding of iron catecholate ligands to NGAL as a central member of the lipocalin family of proteins. This approach provides a modeling basis for exploring in silico the selective binding of iron catecholates ligands giving a detailed picture of their interactions in terms of electrostatic effects and a network of hydrogen bonds in the protein binding pocket.

Complexes of cytotoxic chelators from the dipyridyl ketone isonicotinoyl hydrazone (HPKIH) analogues

In an effort to better understand the antiproliferative effects of the tridentate hydrazone chelators di-2-pyridyl ketone isonicotinoyl hydrazone (HPKIH) and di-2-pyridyl ketone benzoyl hydrazone (HPKBH), we report the coordination chemistry of these ligands with the divalent metal ions, Mn, Co, Ni, Cu, and Zn. These complexes are compared with their Fe-II analogues which were reported previously. The crystal structures of Co(PKIH)(2), Ni(PKIH)(2), Cu(PKIH)(2), Mn(PKBH)(2), Ni(PKBH)(2), Cu(PKBH)(2), and Zn(PKBH)(2) are reported where similar bis-tridenate coordination modes of the ligands are defined. In pure DMF, all complexes except the Zn-II compounds exhibit metal-centered M-III/II (Mn, Fe, Co, Ni) or M-II/I (Cu) redox processes. All complexes show ligand-centered reductions at low potential. Electrochemistry in a mixed water/DMF solvent only elicited metal-centered responses from the Co and Fe complexes. Remarkably, all complexes show antiproliferative activity against the SK-N-MC neuroepithelioma cell line similar to (HPKIH) or significantly greater than that of the (HPKBH) ligand which suggests a mechanism that does not only involve the redox activity of these complexes. In fact, we suggest that the complexes act as lipophilic transport shuttles that allow entrance to the cell and enable the delivery of both the ligand and metal which act in concert to inhibit proliferation.

PCTH: A novel orally active chelator for the treatment of iron overload disease

Our laboratories have prepared a novel class of iron (Fe) chelators of the 2-pyridylcarboxaldehyde isonicotinoyl hydrazone (PCIH) class. This article will review the iron chelation efficacy of this series of chelators, both in cell culture and in animal models. Several PCIH analogs were shown to be effective at inducing iron mobilization and preventing iron uptake from the iron-transport protein, transferrin. Moreover, several of these ligands were effective at permeating the mitochondrion and inducing iron release. Studies in mice demonstrated that the PCIH analog, PCTH, was orally active and well tolerated by mice at doses ranging from 50 to 100 mg kg(-1) , twice daily (b.d.). A dose-dependent increase in fecal Fe-59 excretion was observed in the PCTH-treated group. This level of iron excretion was similar to that found for the orally effective chelators, pyridoxal isonicotinoyl hydrazone (PIH) and deferiprone (L1). The PCIH group of ligands clearly has the potential for the treatment of ss-thalassemia (thal) and Friedreich's Ataxia (FA).

Purification and Characterization of a New Indole Oxygenase from the Leaves of Tecoma stans L.

A new indole oxygenase from the leaves of Tecoma stans was isolated and purified to homogenity. The purified enzyme system catalyzes the conversion of indole to anthranilic acid. It is optimally active at pH 5.2 and 30°C. Two moles of oxygen are consumed and one mole of anthranilic acid is formed for every mole of indole oxidized. Dialysis resulted in complete loss of the activity. The inactive enzyme could be reactivated by the addition of concentrated dialysate. The enzyme is not inhibited by copperspecific chelators, non-heme iron chelators or atebrin. It is not a cuproflavoprotein, unlike the other indole oxygenases and oxidases.

Estudo do reparo das lesões induzidas no DNA de Escherichia coli pela radiação ultravioleta C (UVC)

Didaticamente, podemos dividir o espectro da radiação ultravioleta (UV) em três faixas: UVA (400 a 320 nm), UVB (320 a 290 nm) e UVC (290 a 100 nm). Apesar do UVC ou UV-curto ser eficientemente filtrado pela camada de ozônio da Terra e sua atmosfera, este é uma das faixas do espectro de UV mais usadas para explorar as consequências de danos causados ao DNA, já que a letalidade induzida por este agente está relacionada aos danos diretos no genoma celular, como as lesões dímero de pirimidina, que são letais se não reparadas. Contudo, demonstrou-se que a radiação UVC pode gerar espécies reativas de oxigênio (ERO), como o oxigênio singleto (1O2). Embora, o radical hidroxil (OH) cause modificações oxidativas nas bases de DNA, alguns trabalhos indicam que o 1O2 também está envolvido nos danos oxidativos no DNA. Esta ERO é produzida por vários sistemas biológicos e reações fotossensibilização, quando cromóforos são expostos à luz visível ou são excitados pela luz UV, permitindo que essa energia possa ser transferida para o oxigênio sendo convertido em 1O2, que é conhecido por modificar resíduos de guanina, gerando 8-oxoG, que caso não seja reparada pode gerar uma transversão GC-TA. O objetivo deste trabalho foi o de elucidar a participação de ERO nos efeitos genotóxicos e mutagênicos gerados pela radiação UVC, assim como as enzimas envolvidas no processo de reparação destas lesões em células de Escherichia coli. Nos ensaios as culturas foram irradiadas com o UVC (254 nm; 15W General Electric G15T8 germicidal lamp, USA). Nossos resultados mostram que o uso de quelantes de ferro não alterou a letalidade induzida pelo UVC. A azida sódica, um captador de 1O2, protegeu as cepas contra os danos genotóxicos gerados pelo UVC e também diminuiu a frequência de mutações induzidas no teste com rifampicina. A reversão específica GC-TA foi induzida mais de 2,5 vezes no ensaio de mutagênese. A cepa deficiente na proteína de reparo Fpg, enzima que corrige a lesão 8-oxoG, apresentou menos quebras no DNA do que a cepa selvagem no ensaio de eletroforese alcalina. A letalidade induzida pelo UVC foi aumentada nos mutantes transformados com o plasmídeo pFPG, ao mesmo tempo que representou uma redução na indução mutagênica. Houve dimuição na eficiência de transformação com plasmídeo pUC 9.1 na cepa fpg quando comparado a cepa selvagem. Assim como, um aumento da sensibilidade ao UVC na associação entre mutantes fpg e uvrA. Estes resultados mostram que o 1O2 participa dos danos induzidos pelo UVC, através da geração da lesão 8-oxoG, uma lesão mutagênica, que é reparada pela proteína Fpg

Revaloració de la fracció cel·lular de la sang de porc procedent d'escorxadors industrials

La sang de porc és un subproducte comestible que es genera als escorxadors industrials durant el procés d'obtenció de la canal. Aquest subproducte es caracteritza per presentar una elevada càrrega contaminant i, degut a l'elevat volum que es genera, és necessari trobar estratègies que permetin la seva revaloració i aprofitament, a la vegada que disminuïm la contaminació ambiental i les despeses que es deriven del seu processament abans de l'abocament. La fracció cel·lular (FC) constitueix el 40 % de la sang de porc i conté principalment l'hemoglobina (Hb), que representa al voltant del 90 % del contingut en proteïna d'aquesta fracció (un 35 % aproximadament). L'elevat percentatge en proteïna i en ferro, i les seves bones propietats funcionals fan que l'aprofitament d'aquest subproducte com a primera matèria o ingredient de la indústria alimentària sigui una alternativa molt útil a l'hora de reduir les despeses de la indústria càrnia, sempre que es resolguin els problemes de l'enfosquiment i dels sabors estranys que pot conferir la FC quan s'addiciona a productes alimentaris. Una altra possible utilització de la FC és aprofitar les propietats colorants de l'Hb o del grup hemo, com a colorant d'origen natural en diversos productes alimentaris. Els objectius del present treball eren, en primer lloc, determinar les millors condicions d'aplicació del procés de conservació de la FC mitjançant la deshidratació per atomització i caracteritzar físico-químicament i microbiològica el concentrat d'Hb en pols. En segon lloc, avaluar l'eficàcia de diferents additius antioxidants i/o segrestants del ferro per prevenir l'enfosquiment que pateix la FC durant la deshidratació. En tercer lloc, aplicar tractaments d'altes pressions hidrostàtiques com a procés d'higienització i avaluar els efectes d'aquest tractament sobre la microbiota contaminant, el color i les propietats funcionals de la FC. Finalment, desenvolupar un procés d'obtenció d'hidrolitzats proteics descolorats a partir de l'Hb amb la finalitat d'utilitzar-los com a ingredients nutricionals i/o funcionals. La millor temperatura de deshidratació per atomització de la FC hemolitzada era 140ºC. La FC en pols presentava un contingut en humitat del 5,3 % i un percentatge de solubilitat proteica del 96 %. La deshidratació per atomització induïa canvis en l'estructura nativa de l'Hb i, per tant, un cert grau de desnaturalització que pot conduir a una disminució de les seves propietats funcionals. L'extracte sec de la FC en pols estava composat per un 94,6 % de proteïna, un 3 % de sals minerals i un 0,7 % de greix. Els valors CIE L*a*b* del color de la FC en pols eren força constants i reflectien el color vermell marró fosc d'aquesta, a causa de l'oxidació del ferro hèmic que es produeix durant la deshidratació. La càrrega contaminant de la FC fresca de la sang de porc era força elevada i el tractament d'hemòlisi amb ultrasons i la centrifugació posterior no produïen una reducció significativa de la microbiota contaminant, obtenint un producte amb uns recomptes microbiològics de l'ordre de 106 ufc·mL-1. La deshidratació per atomització produïa una disminució d'una unitat logarítmica dels recomptes totals de la FC hemolitzada. Tanmateix, el producte en pols encara reflectia l'elevada contaminació de la primera matèria, fet que condiciona negativament la seva utilització com a ingredient alimentari, a no ser que es millorin les condicions de recollida de la sang a l'escorxador o que aquesta o la FC es sotmeti a algun tractament d'higienització prèviament a la deshidratació. Les isotermes de sorció a 20ºC de la FC en pols tenien forma sigmoïdal i una histèresi estreta i llarga. L'equació GAB és un bon model matemàtic per ajustar les dades de sorció obtingudes experimentalment i determinar la isoterma d'adsorció de la FC deshidratada per atomització. El percentatge d'humitat de la FC deshidratada a 140ºC es corresponia a un valor d'aw a 20 ºC d'aproximadament el 0,16. Tenint en compte que estava per sota dels valors d'aw corresponents a la capa monomolecular, es pot garantir la conservació a temperatura ambient del producte, sempre que s'envasi en recipients tancats que no permetin l'entrada d'humitat de l'exterior. De l'estudi de la possible estabilització del color de la FC deshidratada per atomització mitjançant l'addició d'antioxidants i/o segrestants de ferro, es va observar que només l'àcid ascòrbic, la glucosa, l'àcid nicotínic i la nicotinamida, tenien efectes positius sobre el color del producte en pols. L'ascòrbic i la glucosa no milloraven la conservació del color de l'Hb però disminuïen l'enfosquiment que es produeix durant la deshidratació, amb la qual cosa es pot obtenir un producte en pols de color marró més clar. L'addició de dextrina o L-cisteïna no disminuïa l'enfosquiment ni evitava el canvi de color de l'Hb. L'àcid nicotínic i la nicotinamida protegien el color de l'Hb durant el procés de deshidratació i l'emmagatzematge de la FC en pols. Les millors condicions d'aplicació del tractament amb altes pressions hidrostàtiques (HHP) sobre la FC eren 400 MPa, a 20ºC, durant 15 minuts, perquè produïen una millora significativa de la qualitat microbiològica, no afectaven negativament al color, no comprometien gaire la solubilitat proteica l'Hb i, malgrat que produïen un augment de la viscositat, la FC romania fluida després del tractament. Aquest tractament permetia una reducció de la microbiota contaminant de la FC d'entre 2 i 3 unitats logarítmiques. L'aplicació de l'alta pressió i la posterior deshidratació per atomització permetien obtenir un producte en pols amb recomptes totals de l'ordre de 2,8 unitats logarítmiques. El color de la FC pressuritzada en pols era igual que el de la FC control deshidratada, perquè ambdues mostres presentaven la mateixa susceptibilitat a l'oxidació del grup hemo produïda per la deshidratació. L'alta pressió incrementava la susceptibilitat de l'Hb als efectes desnaturalitzants de la deshidratació, fonamentalment a pH 7 (PIE), ja que es va observar una disminució de la solubilitat proteica a pH neutre després dels 2 processos tecnològics. La FC en pols presentava una màxima capacitat escumant al PIE de l'Hb. L'aplicació del tractament HHP produïa una disminució de la capacitat escumant de la FC en pols, però no tenia efectes negatius sobre l'estabilitat de l'escuma formada. Tampoc es van observar efectes negatius del tractament HHP sobre l'activitat emulsionant de l'Hb. La màxima activitat emulsionant de l'Hb s'aconseguia amb una concentració de FC en pols de l'1,5 % a pH 7 i de l'1 % a pH 4,5. Les pastes obtingudes per escalfament de la FC presentaven característiques molt diferenciades depenent del pH. A pH neutre es formaven unes pastes dures i consistents, mentre que a pH àcid les pastes eren poc consistents, molt adhesives i més elàstiques que les anteriors. Aquestes tenien una capacitat de retenció d'aigua molt superior que les de pH 7, en les quals l'aigua quedava retinguda per capil·laritat. La textura i capacitat de retenció d'aigua de les pastes tampoc eren afectades pel tractament HHP. El tractament HHP incrementava l'activitat de la Tripsina sobre l'Hb quan el substrat i l'enzim es tractaven conjuntament i afavoria el procés d'obtenció d'hidrolitzats descolorats a partir de la FC, la qual cosa permetia assolir el mateix grau de descoloració amb una dosi d'enzim inferior. El tractament d'hidròlisi de la FC amb la utilització combinada de Tripsina seguida d'un tractament amb Pepsina permetia l'obtenció d'un hidrolitzat proteic d'Hb descolorat i hidrolitzava completament la globina, donant lloc a 2 pèptids de 10,8 i 7,4 KDa. Val a dir que també produïa un 60 80 % de nitrogen soluble en TCA, constituït fonamentalment per pèptids petits i aminoàcids lliures. Els hidrolitzats trípsics i pèpsics d'Hb, obtinguts a partir de FC no pressuritzada i deshidratats per atomització a 180ºC, eren de color blanc i tenien un contingut en humitat del 4,7 %, un 84,2 % de proteïna i 9,7 % de sals minerals. El procés d'hidròlisi permetia una reducció considerable de la contaminació de la FC, obtenint un producte en pols amb uns recomptes totals de l'ordre de 102-103 ufc·g-1. Pel que fa a la funcionalitat dels hidrolitzats d'Hb deshidratats per atomització, aquests presentaven una elevada solubilitat proteica a pH 5 i 7 i romanien solubles després d'un escalfament a 80ºC durant 30 min. Tanmateix, aquesta hidròlisi afectava molt negativament la capacitat de mantenir escumes estables i l'activitat emulsionant.

Thiosemicarbazones, semicarbazones, dithiocarbazates and hydrazide/hydrazones: Anti-Mycobacterium tuberculosis activity and cytotoxicity

The aim of this study was to identify a candidate drug for the development of anti-tuberculosis therapy from previously synthesized compounds based on the thiosemicarbazones, semicarbazones, dithio-carbazates and hydrazide/hydrazones compounds. The minimal inhibitory concentration (MIC) of these compounds against Mycobacterium tuberculosis was determined. Their in vitro cytotoxicity to J774 cells (IC(50)) was determined to establish a selectivity index (SI) (SI = IC(50)/MIC). The best compounds were the thiosemicarbazones (2, 3 and 4) and the hydrazide/hydrazones (14, 15, 16 and 18). The results are comparable to or better than those of ""first line"" or ""second line"" drugs commonly used to treat TB, suggesting these compounds as anti-TB drug candidates. (C) 2010 Elsevier Masson SAS. All rights reserved.

Estudo da ação do ácido trissódio-cálcio-dietileno-triaminopentaacético (CaNa3DTPA) nas lesões de isquemia-reperfusão em membro posterior de rato

Pós-graduação em Bases Gerais da Cirurgia - FMB

Influence of beta(S) allele in the lipid peroxidation and antioxidant capacity parameters

Introduction: The oxidative process plays a fundamental role in the pathophysiology of sickle cell anemia (SCA), and population and environmental characteristics may influence redox balance. The aim of this study was to evaluate lipid peroxidation and antioxidant capacity in Brazilian Hb S carriers undergoing different therapies.MethodsBlood samples from 270 individuals were analyzed (Hb SS, n=68; Hb AS, n=53, and Hb AA, n=149). Hemoglobin genotypes were assessed through cytological, electrophoretic, chromatographic, and molecular methods. Plasma lipid peroxidation and antioxidant capacity were measured by spectrophotometric methods.ResultsPatients with SCA who used iron-chelating drugs combined with hydroxyurea, associated with regular transfusions, showed lower levels of TBARS (P <= 0.05), higher levels of TEAC (P <= 0.01), and lower TBARS/TEAC ratio (R=255.8). The redox profile of Hb AS subjects was not statistically different (P>0.05) from that of Hb AA subjects.ConclusionThe data suggest that oxidative stress is lower in the patients with SCA who received regular blood transfusions associated with the combined use of HU and iron chelators than the group received only HU. The redox system of the Hb AS carriers is compatible with the control group.

2-Acetylpyridine- and 2-benzoylpyridine-derived hydrazones and their gallium(III) complexes are highly cytotoxic to glioma cells

2-Acetylpyridine-phenylhydrazone (H2AcPh), its para-chlorophenylhydrazone (H2AcpClPh) and para-nitrophenylhydrazone (H2AcpNO(2)Ph) analogues, the corresponding 2-benzoylpyridine-derived hydrazones (H2BzPh, H2BzpClPh and H2BzpNO(2)Ph) and their gallium(III) complexes were assayed for their cytotoxic activity against U87 (expressing wild-type p53 protein) and T98 (expressing mutant p53 protein) glioma cells. IC50 values against both glioma cells and against the MRC5 (human fetal lung fibroblast) lineage were obtained for the hydrazones, but not for their gallium(III) complexes, due to their low solubility. Hydrazones were highly cytotoxic at nanomolar doses against U87 and T98 cells. The therapeutic indexes (TI = IC50MRC5/IC50glioma) were 2-660 for T98 cells and 28-5000 for U87 cells, indicating that the studied hydrazones could be good antitumor drug candidates to treat brain tumors. (C) 2012 Elsevier Masson SAS. All rights reserved.

Size exclusion chromatogram of the Tannermoor 2009 sample after saltout experiments

Samples from a pristine raised peat bog runoff in Austria, the Tannermoor creek, were analysed for their iron linked to natural organic matter (NOM) content. Dissolved organic carbon < 0.45 µm (DOC) was 41 to 64 mg/L, iron 4.4 to 5.5 mg/L. Samples were analysed applying asymmetric field flow fractionation (AsFlFFF) coupled to UV-Vis absorption, fluorescence and inductively coupled plasma mass spectrometry (ICP-MS). The samples showed an iron peak associated with the NOM peak, one sample exhibiting a second peak of iron independent from the NOM peak. As highland peat bogs with similar climatic conditions and vegetation to the Tanner Moor are found throughout the world, including areas adjacent to the sea, we examined the behaviour of NOM and iron in samples brought to euhaline (35 per mil) conditions with artificial sea salt. The enhanced ionic strength reduced NOM by 53% and iron by 82%. Size exclusion chromatography (SEC) of the samples at sea-like salinity revealed two major fractions of NOM associated with different iron concentrations. The larger one, eluting sharply after the upper exclusion limits of 4000-5000 g/mol, seems to be most important for iron chelating. The results outline the global importance of sub-mountainous and mountainous raised peat bogs as a source of iron chelators to the marine environment at sites where such peat bogs release their run-offs into the sea.