Szinergizmus az ozmium-tetroxid és perjodátion redoxireakcióiban = Synergism in the redox reactions of osmium tetroxide and periodate ion

A projektben az ozmium-tetroxid és a perjodátion oxidációs reakcióiban tapasztalható szinergikus hatást vizsgáltuk. Ilyen hatásról elsőként a metán metanollá való oxidációjában számoltak be, ennek a folyamatnak igen nagy jelentősége lehet a földgázszállítás fejlesztésében. A szinergikus hatást legrészletesebben jodidion és formiátion redukálószerek használatával tanulmányoztuk. Igen összetett kinetikai jelenségekre bukkantuk. A szinergikus hatás több lehetséges magyarázatát kizártuk, végül lényegében az egyetlen, a kísérleti tényeknek ellent nem mondó lehetőség az maradt, hogy a ozmium-tetroxid katalizálja a perjodátion két különböző, és oxidációs folyamatokban is jelentősen eltérő reakcióképességű formájának egymásba alakulását. A tanulmányozott folyamatok minél alaposabb megismerése érdekében megvizsgáltuk a jodidion fotokémiai reakcióit, ehhez külön módszert dolgoztunk ki diódasoros spektrofotométer felhasználásával, s az ehhez szükséges aktinometriás kalibrálási módszert is továbbfejlesztettük. Az ozmium-tetroxid és néhány klórozott olefin reakciójának vizsgálata során is sikerült új, eddig még nem tanulmányozott folyamatokat megfigyelnünk. Igazoltuk, hogy a klórozott olefinek lúgos közegben vízzel izotópcsere-reakcióban vesznek részt. Mindezen eredmények lehetővé teszik a metán oxidációjának jobb megértését is, s ezen keresztül alapot szolgáltathatnak ipari módszerek kifejlesztéséhez. | In this project, the synergistic effect observed in oxidation reactions containing osmium tetroxide and periodate ion was studied in detail. This phenomenon was first reported during the oxidation of methane to methanol, a process with significant industrial potential in the transportation of natural gas. The synergistic effect was exhaustively studies using iodide ion and periodate ion as reducing agents. Very complicated kinetic patters were unveiled. Several different interpretations of this effect were excluded. Finally, the only theory that did not contradict the experimental results remained that osmium tetroxide must catalyze the interconversion of the octahedral and tetrahedral forms of periodate ion, which have significantly different reactivity in oxidation reactions. To understand the studied processes even deeper, the photochemical reactions of the iodide ion were also studied. For this purpose, a novel method using a diode array spectrophotometer was developed, and the actinometric calibration process necessary in these investigations was significantly improved. The reaction between osmium tetroxide and a few chlorinated olefins were also studied, and novel kinetic phenomena have been found in these systems. It was demonstrated that an isotope exchange reactions occurs under aqueous basic conditions. These results provide a deep insight into the mechanisms of the oxidation of methane, and could provide a basis for the development of industrial methods

Kinetic Inertness of the Mn Complexes Formed with AAZTA and Some Open-Chain EDTA Derivatives

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Chapter 5.2 The Future of Biomedical Imaging: Synthesis and Chemical Properties of the DTPA and DOTA Derivative Ligands and Their Complexes

The chelate complexes of lanthanides and some other trivalent metal ions are widely used in medical diagnosis and therapy (MRI contrast agents, Optical Imaging, Nuclear Medicine). The chelating agents are mostly aminopolycarboxylate ligands, the open-chain DTPA, the macrocyclic DOTA and their derivatives. This Chapter describes the most important synthetic methods used for the preparation of the ligands (including some bifunctional chelators) and their complexes. The behaviour of the metal complexes in biological systems strongly depends on their equilibrium and kinetic properties. A short review on the methods used to determine the protonation constants of ligands, the stability constants of the complexes and the stability data reported, help to understand the in vivo equilibrium behaviour of metal chelates. The safety of gadolinium based MRI contrast agents strongly depends on the kinetic inertness of the complexes which is characterized with the rate data reported for the transmetallation reactions occurring between the complexes and Zn2+ or Cu2+ ions. The summary on transmetallation kinetics of the complexes formed with DTPA and DOTA derivative ligands are also summarized in the current Chapter. The rate data obtained in the presence of the endogenous citrate are in harmony with the results of biodistribution studies, indicating that the amount of retained Gd is largest for the Gd(DTPA-BMA)

Lantanida(III) dietiléntriamin-pentaacetát származékokkal képződő komplexek ligandumcsere reakcióinak kinetikája. A nemkovalens kölcsönhatások szerepe. = Kinetics of ligand exchange reactions of lanthanide(III) complexes formed with the derivatives of diethylenetriaminepentaacetate. The role of non-covalent interactions.

Hidrofób csoportot tartalmazó Gd3+-komplexek és beta-ciklodextrin vagy fehérjék nem-kovalens kölcsönhatása növeli a relaxivitást, de a komplexek stabilitását, inertségét csak kismértékben befolyásolja. A Gd(DTPA), Gd(BOPTA) és Gd(DTPA-BMA) komplexek (GdL) és a TTHA közötti ligandumcsere másodrendű reakcióként megy végbe. A GdL komplexek és Cu2+ vagy Zn2+ közötti fémioncsere reakciók citrát, foszfát, karbonát és hisztidinát jelenlétében a komplexek endogén ligandumok által segített disszociációjával folynak le. A Gd(DTPA-BMA) ligandumcsere és fémioncsere reakciói a gyorsabb intramolekuláris átrendeződések miatt sokkal gyorsabbak, mint a Gd(DTPA) és Gd(BOPTA) komplexeké. A nyolcfunkciós BCAED és BCAEP ligandumok Ln3+ komplexei logKLnL értékei nagymértékben nőnek a La-tól a Lu-ig. A Sm(EDTMP) és Ho(EDTMP) stabilitási állandói nagyok, de a fémcsere reakcióik Cu2+-citráttal gyorsan végbemennek pH 7 – 9 között a komplex proton katalizált disszociációjával. A makrociklusos DO2A2P ligandum Ln3+-komplexeinek sajátosságai (stabilitás, szerkezet, képződés és disszociáció sebesség) a Ln(DOTA) és Ln(DOTP) hasonló sajátosságai közötti értéküek. | The non-covalent interaction between the Gd3+-complexes, containing hydrophobic groups, and beta-cyclodextrin or proteins result in the increase of the relaxivities, but the stability constants and the kinetic inertness of complexes is only slightly influenced. The ligand exchange between the Gd(DTPA), Gd(BOPTA) and Gd(DTPA-BMA) complexes (GdL) and TTHA occurs in second order reactions. The metal exchange reactions between the GdL complexes and Cu2+ or Zn2+, in the presence of citrate, phosphate, carbonate and histidinate, take place with the dissociation of complexes, assisted by the endogenous ligands. The ligand and metal exchange reactions of Gd(DTPA-BMA) are much faster than those of the Gd(DTPA) and Gd(BOPTA), because the intramolecular rearrangements in Gd(DTPA-BMA) are faster. The logKLnL values obtained for the Ln3+-complexes of the octadentate BCAED and BCAEP ligands increase to a great extent from La to Lu. In spite of the high stability constants of Sm(EDTMP) and Ho(EDTMP), their exchange reactions with Cu2+-citrate are fast and occur with the proton assisted dissociation of complexes in the pH range 7 – 9. The properties of the macrocyclic Ln(DO2A2P) complexes (stability, structure, formation and dissociation rates) were found to be amongst the similar properties of Gd(DOTA) and Gd(DOTP)

Physico-chemical properties of MnII complexes formed with cis- and trans-DO2A: thermodynamic, electrochemical and kinetic studies

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Rigidified Derivative of the Non-macrocyclic Ligand H₄OCTAPA for Stable Lanthanide(III) Complexation

Financiado para publicación en acceso aberto: Universidade da Coruña/CISUG[Abstract] The stability constants of lanthanide complexes with the potentially octadentate ligand CHXOCTAPA4–, which contains a rigid 1,2-diaminocyclohexane scaffold functionalized with two acetate and two picolinate pendant arms, reveal the formation of stable complexes [log KLaL = 17.82(1) and log KYbL = 19.65(1)]. Luminescence studies on the Eu3+ and Tb3+ analogues evidenced rather high emission quantum yields of 3.4 and 11%, respectively. The emission lifetimes recorded in H2O and D2O solutions indicate the presence of a water molecule coordinated to the metal ion. 1H nuclear magnetic relaxation dispersion profiles and 17O NMR chemical shift and relaxation measurements point to a rather low water exchange rate of the coordinated water molecule (kex298 = 1.58 × 106 s–1) and relatively high relaxivities of 5.6 and 4.5 mM–1 s–1 at 20 MHz and 25 and 37 °C, respectively. Density functional theory calculations and analysis of the paramagnetic shifts induced by Yb3+ indicate that the complexes adopt an unprecedented cis geometry with the two picolinate groups situated on the same side of the coordination sphere. Dissociation kinetics experiments were conducted by investigating the exchange reactions of LuL occurring with Cu2+. The results confirmed the beneficial effect of the rigid cyclohexyl group on the inertness of the Lu3+ complex. Complex dissociation occurs following proton- and metal-assisted pathways. The latter is relatively efficient at neutral pH, thanks to the formation of a heterodinuclear hydroxo complex.F.L.-M., D.E.-G., and C.P.-I. thank Ministerio de Ciencia e Innovación (Grant PID2019-104626GB-I00) and Xunta de Galicia (ED431B 2020/52) for generous financial support. The authors thank the financial support for the Hungarian National Research, Development and Innovation Office (NKFIH K-128201, 134694 and FK-134551 projects). G.T. and C.P.-I. gratefully acknowledge the bilateral Hungarian–Spanish Science and Technology Cooperation Program (2019-2.1.11-TET-2019-00084 supported by NKFIH). B.V. was supported by the Doctoral School of Chemistry at the University of Debrecen, Debrecen, Hungary. This publication and the scientific research were supported by the Gedeon Richter’s Talentum Foundation established by Gedeon Richter Plc (Gedeon Richter Ph.D. Fellowship). The research was prepared with the professional support of the Doctoral Student Scholarship Program of the Cooperative Doctoral Program of the Ministry of Innovation and Technology financed from the National Research, Development and Innovation Fund (NKFIH). The research was supported by the ÚNKP-21-4 new national excellence program of the Ministry of Human Capacities (F.K.K.) and the János Bolyai Research Scholarship of the Hungarian Academy of Sciences (F.K.K.). The authors are indebted to Centro de Supercomputación de Galicia (CESGA) for providing the computer facilities. C.P.-I. thanks Prof. M. Mazzanti for noticing that the emission quantum yields reported previously for OCTAPA4– complexes were incorrect. Funding for open access provided by Universidade da Coruña/CISUGXunta de Galicia; ED431B 2020/52Hungary. National Research, Development and Innovation Office; NKFIH K-128201Hungary. National Research, Development and Innovation Office; NKFIH K-134694Hungary. National Research, Development and Innovation Office; NKFIH FK-134551Hungary. National Research, Development and Innovation Office; 2019-2.1.11-TET-2019-00084Hungary. Ministry of Human Capacities; ÚNKP-21-

Complexes of bifunctional DO3A-N-(α-amino)propinate ligands with Mg(II), Ca(II), Cu(II), Zn(II), and lanthanide(III) ions: thermodynamic stability, formation and dissociation kinetics, and solution dynamic NMR studies

The thermodynamic, kinetic, and structural properties of Ln3+ complexes with the bifunctional DO3A-ACE4− ligand and its amide derivative DO3A-BACE4− (modelling the case where DO3A-ACE4− ligand binds to vector molecules) have been studied in order to confirm the usefulness of the corresponding Gd3+ complexes as relaxation labels of targeted MRI contrast agents. The stability constants of the Mg2+ and Ca2+ complexes of DO3A-ACE4− and DO3A-BACE4− complexes are lower than for DOTA4− and DO3A3−, while the Zn2+ and Cu2+ complexes have similar and higher stability than for DOTA4− and DO3A3− complexes. The stability constants of the Ln(DO3A-BACE)− complexes increase from Ce3+ to Gd3+ but remain practically constant for the late Ln3+ ions (represented by Yb3+). The stability constants of the Ln(DO3A-ACE)4− and Ln(DO3A-BACE)4− complexes are several orders of magnitude lower than those of the corresponding DOTA4− and DO3A3− complexes. The formation rate of Eu(DO3A-ACE)− is one order of magnitude slower than for Eu(DOTA)−, due to the presence of the protonated amine group, which destabilizes the protonated intermediate complex. This protonated group causes the Ln(DO3A-ACE)− complexes to dissociate several orders of magnitude faster than Ln(DOTA)− and its absence in the Ln(DO3A-BACE)− complexes results in inertness similar to Ln(DOTA)− (as judged by the rate constants of acid assisted dissociation). The 1H NMR spectra of the diamagnetic Y(DO3A-ACE)− and Y(DO3A-BACE)− reflect the slow dynamics at low temperatures of the intramolecular isomerization process between the SA pair of enantiomers, R-Λ(λλλλ) and S-Δ(δδδδ). The conformation of the Cα-substituted pendant arm is different in the two complexes, where the bulky substituent is further away from the macrocyclic ring in Y(DO3A-BACE)− than the amino group in Y(DO3A-ACE)− to minimize steric hindrance. The temperature dependence of the spectra reflects slower ring motions than pendant arms rearrangements in both complexes. Although losing some thermodynamic stability relative to Gd(DOTA)−, Gd(DO3A-BACE)− is still quite inert, indicating the usefulness of the bifunctional DO3A-ACE4− in the design of GBCAs and Ln3+-based tags for protein structural NMR analysis.This research was funded by the Hungarian National Research, Development and Innovation Office (Projects NKFIH K-128201, K-134694, and FK-134551)

Stable and inert macrocyclic cobalt(ii) and nickel(ii) complexes with paraCEST response

We report the synthesis of the macrocyclic ligands 3,9 PC2AMH (2,2’-(3,6,9-triaza-1(2,6)-pyridinacyclodecaphane-3,9-diyl)diacetamide) and 3,9-PC2AMtBu (2,2’-(3,6,9-triaza-1(2,6)-pyridinacyclodecaphane-3,9-diyl)bis(N-tert-butyl)acetamide) which contain a pyclen platform functionalized with acetamide or tert-butylacetamide pendant arms at positions 3 and 9 of the macrocyclic unit. The corresponding Co(II) and Ni(II) complexes were prepared, isolated and characterised as potential paramagnetic chemical exchange saturation transfer (paraCEST) agents. The X-ray structures of the Ni(II) complexes reveal six-coordination of the ligands to the metal ion. The Co(II) complex with 3,9-PC2AMtBu shows a similar six-coordinate structure in the solid state, while the Co(II) complex with 3,9 PC2AMH contains a seven-coordinate metal ion, seventh coordination being completed by the presence of an inner-sphere water molecule. The structure of the Co(II) complexes was investigated using 1H NMR spectroscopy and computational methods. The complexes present a seven-coordinate structure in solution, as demonstrated by the analysis of the paramagnetic shifts using density functional theory. Ligand protonation constants and stability constants of the complexes with 3,9 PC2AMH were determined using potentiometric titrations (I=0,15 M NaCl). The Co(II) complex was found to be more stable than the Ni(II) analogue (log KCoL = 14.46(5) and log KNiL = 13.15(3)). However, the Ni(II) and Co(II) complexes display similar rate constants characterizing the proton-assisted dissociation mechanism. The presence of highly shifted 1H NMR signals due to the amide protons in slow exchange with bulk water results in sizeable CEST signals, which are observed at +67 and +15 ppm for the Co(II) complex with 3,9 PC2AMH and +42 and +7 ppm for the Ni(II) analogue at 25ºC .Agencia Estatal de Investigación | Ref. CTQ2016-76756-PXunta de Galicia | Ref. ED431B 2020/52Nemzeti Kutatási Fejlesztési és Innovációs Hivatal | Ref. K-120224Nemzeti Kutatási Fejlesztési és Innovációs Hivatal | Ref. K-134694Science and Technology Commission of Shanghai Municipality | Ref. 2019SHZDZX0