Vurdering av utslippspunkt for nytt renseanlegg i Drammensfjorden

Prosjektleder: André StaalstrømDet planlegges å bygge et nytt sentralt renseanlegg i Drammen, og i denne rapporten har virkningen av utslippsdyp fra 30 til 90 m blitt vurdert. På grunn av økt vertikal blanding så vil oksygenforholdene i vannmassene bli bedre. Virkningen er best om utslippet slippes ut på 90 m dyp, men dette vil kreve at det bygges en 1,7-km lang avløpsledning. Det vil også være god effekt på oksygenforholdene om utslippet legges på 70-80 m som vil krev en betydelig kortere avløpsledning. Effekten av økte oksygenkonsentrasjoner over bunn vil virke positivt inn på miljøgifter i sedimentene ved at organiske stoffer brytes ned raskere og tungmetaller vil sedimentere raskere.Drammen, Asker og Lier kommunepublishedVersio

Synthesis, Characterization, and Biological Studies of a Piperidinyl Appended Dipicolylamine Ligand and Its Rhenium Tricarbonyl Complex as Potential Therapeutic Agents for Human Breast Cancer

© 2016 Amali Subasinghe et al. A novel ligand bearing a central piperidinyl sulfonamide group, N(SO2pip)dpa, and its corresponding Re tricarbonyl complex, [Re(CO)3(N(SO2pip)dpa)]+, have been synthesized in good yield. The methylene CH2 signal seen as a singlet (4.54 ppm) in a 1H NMR spectrum of the ligand in DMSO-d6 appears as two doublets (5.39, 5.01 ppm) in a spectrum of the [Re(CO)3(N(SO2pip)dpa)]+ complex and confirms the presence of magnetically nonequivalent protons upon coordination to Re. Structural results revealed that the Re-N bond lengths fall within the normal range establishing coordination of ligand to metal. The presence of intraligand π→π and n→π transitions is indicated by the absorption peaks around 200-250 nm in UV-visible spectra. Absorption peaks in UV-visible spectra around 300 nm for metal complexes were identified as MLCT transitions. The S-N stretch observed as a strong peak at 923 cm-1 for N(SO2pip)dpa appeared at a shorter frequency, at 830 cm-1 in an FTIR spectrum of the [Re(CO)3(N(SO2pip)dpa)]+. The intense fluorescence displayed by the N(SO2pip)dpa ligand has quenched upon coordination to Re. Relatively low IC50 values given by human breast cancer cells, MCF-7, (N(SO2pip)dpa = 139 μM, [Re(CO)3(N(SO2pip)dpa)]+ = 360 μM) indicate that N(SO2pip)dpa and [Re(CO)3(N(SO2pip)dpa)]+ are promising novel compounds that can be further investigated on their usage as potential anticancer agents

A Very Rare Example of a Structurally Characterized 3′-GMP Metal Complex. NMR and Synthetic Assessment of Adducts Formed by Guanine Derivatives with [Pt(L\u3csup\u3etri\u3c/sup\u3e)Cl]Cl Complexes with an N,N′,N″ Tridentate Ligand (L\u3csup\u3etri\u3c/sup\u3e) Terminated by Imidazole Rings

© 2017 American Chemical Society. [Pt(N(R)-1,1′-Me2dma)Cl]Cl complexes with tridentate ligands (bis(1-methyl-2-methylimidazolyl)amine, R = H; N-(methyl)bis(1-methyl-2-methylimidazolyl)amine, R = Me) were prepared in order to investigate Pt(N(R)-1,1′-Me2dma)G adducts (G = monodentate N9-substituted guanine or hypoxanthine derivative). Solution NMR spectroscopy is the primary tool for studying metal complexes of nucleosides and nucleotides because such adducts rarely crystallize. However, [Pt(N(H)-1,1′-Me2dma)(3′-GMPH)]NO3·5H2O (5) was crystallized, allowing, to our knowledge, the first crystallographic molecular structure determination for a 3′-GMP platinum complex. The structure is one of only a very few structures of a 3′-GMP complex with any metal. Complex 5 has the syn rotamer conformation, with 3′-GMP bound by N7. All Pt(N(R)-1,1′-Me2dma)G adducts exhibit two new downfield-shifted G H8 signals, consistent with G bound to platinum by N7 and a syn/anti rotamer mixture. Anticancer-active monofunctional platinum(II) complexes have bulky carrier ligands that cause DNA adducts to be distorted. Hence, understanding carrier-ligand steric effects is key in designing new platinum drugs. Ligand bulk can be correlated with the degree of impeded rotation of the G nucleobase about the Pt-N7 bond, as assessed by the observation of rotamers. The signals of syn and anti rotamers are connected by EXSY cross-peaks in 2D ROESY spectra of Pt(N(H)-1,1′-Me2dma)G adducts but not in spectra of Pt(N(H)dpa)G adducts (N(H)dpa = bis(2-picolyl)amine), indicating that rotamer interchange is more facile and carrier-ligand bulk is lower in Pt(N(H)-1,1′-Me2dma)G than in Pt(N(H)dpa)G adducts. The lower steric hindrance is a direct consequence of the greater distance of the G nucleobase from the H4/4′ protons in the N(R)-1,1′-Me2dma carrier ligand in comparison to that from the H6/6′ protons in the N(H)dpa carrier ligand. Although in 5 the nucleotide is 3′-GMP (not the usual 5′-GMP) and the N(H)-1,1′-Me2dma carrier ligand is very different from those typically present in structurally characterized Pt(II) G complexes, the rocking and canting angles in 5 adhere to long-recognized trends

Linear Bidentate Ligands (L) with Two Terminal Pyridyl N-Donor Groups Forming Pt(II)LCl\u3csub\u3e2\u3c/sub\u3e Complexes with Rare Eight-Membered Chelate Rings

Copyright © 2018 American Chemical Society. NMR and X-ray diffraction studies were conducted on Pt(II)LCl2 complexes prepared with the new N-donor ligands N(SO2R)Mendpa (R = Me, Tol; n = 2, 4). These ligands differ from N(H)dpa (di-2-picolylamine) in having the central N within a tertiary sulfonamide group instead of a secondary amine group and having Me groups at the 6,6′-positions (n = 2) or 3,3′,5,5′-positions (n = 4) of the pyridyl rings. The N(SO2R)3,3′,5,5′-Me4dpa ligands are coordinated in a bidentate fashion in Pt(N(SO2R)3,3′,5,5′-Me4dpa)Cl2 complexes, forming a rare eight-membered chelate ring. The sulfonamide N atom did not bind to Pt(II), consistent with indications in the literature that tertiary sulfonamides are unlikely to anchor two meridionally coordinated five-membered chelate rings in solutions of coordinating solvents. The N(SO2R)6,6′-Me2dpa ligands coordinate in a monodentate fashion to form the binuclear complexes [trans-Pt(DMSO)Cl2]2(N(SO2R)6,6′-Me2dpa). The monodentate instead of bidentate N(SO2R)6,6′-Me2dpa coordination is attributed to 6,6′-Me steric bulk. These binuclear complexes are indefinitely stable in DMF-d7, but in DMSO-d6 the N(SO2R)6,6′-Me2dpa ligands dissociate completely. In DMSO-d6, the bidentate ligands in Pt(N(SO2R)3,3′,5,5′-Me4dpa)Cl2 complexes also dissociate, but incompletely; these complexes provide rare examples of association-dissociation equilibria of N,N bidentate ligands in Pt(II) chemistry. Like typical cis-PtLCl2 complexes, the Pt(N(SO2R)3,3′,5,5′-Me4dpa)Cl2 complexes undergo monosolvolysis in DMSO-d6 to form the [Pt(N(SO2R)3,3′,5,5′-Me4dpa)(DMSO-d6)Cl]+ cations. However, unlike typical cis-PtLCl2 complexes, the Pt(N(SO2R)3,3′,5,5′-Me4dpa)Cl2 complexes surprisingly do not react readily with the excellent N-donor bioligand guanosine. A comparison of the structural features of over 50 known relevant Pt(II) complexes having smaller chelate rings with those of the very few relevant Pt(II) complexes having eight-membered chelate rings indicates that the pyridyl rings in Pt(N(SO2R)3,3′,5,5′-Me4dpa)Cl2 complexes are well positioned to form strong Pt-N bonds. Therefore, the dissociation of the bidentate ligand and the poor biomolecule reactivity of the Pt(N(SO2R)3,3′,5,5′-Me4dpa)Cl2 complexes arise from steric consequences imposed by the -CH2-N(SO2R)-CH2- chain in the eight-membered chelate ring

Glycine N-methyltransferases: A comparison of the crystal structures and kinetic properties of recombinant human, mouse and rat enzymes

Glycine N-methyltransferases (GNMTs) from three mammalian sources were compared with respect to their crystal structures and kinetic parameters. The crystal structure for the rat enzyme was published previously. Human and mouse GNMT were expressed in Escherichia coli in order to determine their crystal structures. Mouse GNMT was crystallized in two crystal forms, a monoclinic form and a tetragonal form. Comparison of the three structures reveals subtle differences, which may relate to the different kinetic properties of the enzymes. The flexible character of several loops surrounding the active site, along with an analysis of the active site boundaries, indicates that the observed conformations of human and mouse GNMTs are more open than that of the rat enzyme. There is an increase in kcat when going from rat to mouse to human, suggesting a correlation with the increased flexibility of some structural elements of the respective enzymes. © 2004 Wiley-Liss, Inc

Structural and biochemical insights into the mechanism of fosfomycin phosphorylation by fosfomycin resistance kinase FomA

We present here the crystal structures of fosfomycin resistance protein (FomA) complexed with MgATP, with ATP and fosfomycin, with MgADP and fosfomycin vanadate, with MgADP and the product of the enzymatic reaction, fosfomycin monophosphate, and with ADP at 1.87, 1.58, 1.85, 1.57, and 1.85 Å resolution, respectively. Structures of these complexes that approximate different reaction steps allowed us to distinguish the catalytically active conformation of ATP and to reconstruct the model of the MgATP•fosfomycin complex. According to the model, the triphosphate tail of the nucleotide is aligned toward the phosphonate moiety of fosfomycin, in contast to the previously published MgAMPPNP complex, with the attacking fosfomycin oxygen positioned 4 Å from the γ-phosphorus of ATP. Site-directed mutagenesis studies and comparison of these structures with that of homologous N-acetyl-l-glutamate and isopentenyl phosphate kinases allowed us to propose a model of phosphorylation of fosfomycin by FomA enzyme. A Mg cation ligates all three phosphate groups of ATP and together with positively charged K216, K9, K18, and H58 participates in the dissipation of negative charge during phosphoryl transfer, indicating that the transferred phosphate group is highly negatively charged, which would be expected for an associative mechanism. K216 polarizes the γ-phosphoryl group of ATP. K9, K18, and H58 participate in stabilization of the transition state. D150 and D208 play organizational roles in catalysis. S148, S149, and T210 participate in fosfomycin binding, with T210 being crucial for catalysis. Hence, it appears that as in the homologous enzymes, FomA-catalyzed phosphoryl transfer takes place by an in-line predominantly associative mechanism. © 2011 American Chemical Society

Synthesis and Characterization of Pt(II) Complexes with Pyridyl Ligands: Elongated Octahedral Ion Pairs and Other Factors Influencing \u3csup\u3e1\u3c/sup\u3eH NMR Spectra

© 2017 American Chemical Society. Our goal is to develop convenient methods for obtaining trans-[PtII(4-Xpy)2Cl2] complexes applicable to 4-substituted pyridines (4-Xpy) with limited volatility and water solubility, properties typical of 4-Xpy, with X being a moiety targeting drug delivery. Treatment of cis-[PtII(DMSO)2Cl2] (DMSO = dimethyl sulfoxide) with 4-Xpy in acetonitrile allowed isolation of a new series of simple trans-[PtII(4-Xpy)2Cl2] complexes. A side product with very downfield H2/6 signals led to our synthesis of a series of new [PtII(4-Xpy)4]Cl2 salts. For both series in CDCl3, the size of the H2/6 δ[coordinated minus free 4-Xpy H2/6 shift] decreased as 4-Xpy donor ability increased from 4-CNpy to 4-Me2Npy. This finding can be attributed to the greater synergistic reduction in the inductive effect of the Pt(II) center with increased 4-Xpy donor ability. The high solubility of [PtII(4-Xpy)4]Cl2 salts in CDCl3 (a solvent with low polarity) and the very downfield shift of the [PtII(4-Xpy)4]Cl2 H2/6 signals for the solutions provide evidence for the presence of strong {[PtII(4-Xpy)4]2+,2Cl-} ion pairs that are stabilized by multiple CH···Cl contacts. This conclusion gains considerable support from [PtII(4-Xpy)4]Cl2 crystal structures revealing that a chloride anion occupies a pseudoaxial position with nonbonding (py)C-H···Cl contacts (2.4-3.0 Å). Evidence for (py)C-H···Y contacts was obtained in NMR studies of [PtII(4-Xpy)4]Y2 salts with Y counterions less capable of forming H-bonds than chloride ion. Our synthetic approaches and spectroscopic analysis are clearly applicable to other nonvolatile ligands

Differences in folate-protein interactions result in differing inhibition of native rat liver and recombinant glycine N-methyltransferase by 5-methyltetrahydrofolate

Glycine N-methyltransferase (GNMT) is a key regulatory enzyme in methyl group metabolism. In mammalian liver it reduces S-adenosylmethionine levels by using it to methylate glycine, producing N-methylglycine (sarcosine) and S-adenosylhomocysteine. GNMT is inhibited by binding two molecules of 5-methyltetrahydrofolate (mono- or polyglutamate forms) per tetramer of the active enzyme. Inhibition is sensitive to the status of the N-terminal valine of GNMT and to polyglutamation of the folate inhibitor. It is inhibited by pentaglutamate form more efficiently compared to monoglutamate form. The native rat liver GNMT contains an acetylated N-terminal valine and is inhibited much more efficiently compared to the recombinant protein expressed in E. coli where the N-terminus is not acetylated. In this work we used a protein crystallography approach to evaluate the structural basis for these differences. We show that in the folate-GNMT complexes with the native enzyme, two folate molecules establish three and four hydrogen bonds with the protein. In the folate-recombinant GNMT complex only one hydrogen bond is established. This difference results in more effective inhibition by folate of the native liver GNMT activity compared to the recombinant enzyme. © 2011 Elsevier B.V. All rights reserved