Metal-ion-coordinating properties of the dinucleotide 2'-deoxyguanylyl(5'-->3')-2'-deoxy-5'-guanylate (d(pGpG)3-): isomeric equilibria including macrochelated complexes relevant for nucleic acids

The interaction between divalent metal ions and nucleic acids is well known, yet knowledge about the strength of binding of labile metal ions at the various sites is very scarce. We have therefore studied the stabilities of complexes formed between the nucleic acid model d(pGpG) and the essential metal ions Mg2+ and Zn2+ as well as with the generally toxic ions Cd2+ and Pb2+ by potentiometric pH titrations; all four ions are of relevance in ribozyme chemistry. A comparison of the present results with earlier data obtained for M(pUpU)- complexes allows the conclusion that phosphate-bound Mg2+ and Cd2+ form macrochelates by interaction with N7, whereas the also phosphate-coordinated Pb2+ forms a 10-membered chelate with the neighboring phosphate diester bridge. Zn2+ forms both types of chelates with formation degrees of about 91% and 2.4% for Zn[d(pGpG)]cl/N7 and Zn[d(pGpG)]-cl/PO, respectively; the open form with Zn2+ bound only to the terminal phosphate group, Zn[d(pGpG)]-op, amounts to about 6.8 %. The various intramolecular equilibria have also been quantified for the other metal ions. Zn2+, Cu2+, and Cd2+ also form macrochelates in the monoprotonated M[H;d(pGpG)] species (the proton being at the terminal phosphate group), that is, the metal ion at N7 interacts to some extent with the P(O)2(OH)- group. Thus, this study demonstrates that the coordinating properties of the various metal ions toward a pGpG unit in a nucleic acid differ: Mg2+, Zn2+, and Cd2+ have a significant tendency to bridge the distance between N7 and the phosphate group of a (d)GMP unit, although to various extents, whereas Pb2+ (and possibly Ca2+) prefer a pure phosphate coordination.     

Acid-base properties of xanthosine 5'-monophosphate (XMP) and of some related nucleobase derivatives in aqueous solution: micro acidity constant evaluations of the (N1)H versus the (N3)H deprotonation ambiguity

The first acidity constant of fully protonated xanthosine 5'-monophosphate, that is, of H3(XMP)+, was estimated by means of a micro acidity constant scheme and the following three deprotonations of the H2(XMP)+/- (pKa=0.97), H(XMP)- (5.30), and XMP2- (6.45) species were determined by potentiometric pH titrations; further deprotonation of (XMP-H)3- is possible only with pKa>12. The most important results are that the xanthine residue is deprotonated before the P(O)2(OH)- group loses its final proton; that is, twofold negatively charged XMP carries one negative charge in the pyrimidine ring and one at the phosphate group. Micro acidity constant evaluations reveal that this latter mentioned species occurs with a formation degree of 88 %, whereas its tautomer with a neutral xanthine moiety and a PO3(2-) group is formed only to 12 %; this distinguishes XMP from its related nucleoside 5'-monophosphates, like guanosine 5'-monophosphate. At the physiological pH of about 7.5 mainly (XMP-H)3- exists. The question, which of the purine sites, (N1)H or (N3)H, is deprotonated in this species cannot be answered unequivocally, though it appears that the (N3)H site is more acidic. By application of several methylated xanthine species intrinsic micro acidity constants are calculated and it is shown that, for example, for 7-methylxanthine the N1-deprotonated tautomer occurs with a formation degree of about 5 %; a small but significant amount that, as is discussed, may possibly be enhanced by metal ion coordination to N7, which is known to occur preferably to this site.     

Comparison of the surprising metal-ion-binding properties of 5- and 6-uracilmethylphosphonate (5Umpa2- and 6Umpa2-) in aqueous solution and crystal structures of the dimethyl and di(isopropyl) esters of H2(6Umpa)

5- and 6-Uracilmethylphosphonate (5Umpa(2-) and 6Umpa(2-)) as acyclic nucleotide analogues are in the focus of anticancer and antiviral research. Connected metabolic reactions involve metal ions; therefore, we determined the stability constants of M(Umpa) complexes (M(2+)=Mg(2+), Ca(2+), Mn(2+), Co(2+), Cu(2+), Zn(2+), or Cd(2+)). However, the coordination chemistry of these Umpa species is also of interest in its own right, for example, the phosphonate-coordinated M(2+) interacts with (C4)O to form seven-membered chelates with 5Umpa(2-), thus leading to intramolecular equilibria between open (op) and closed (cl) isomers. No such interaction occurs with 6Umpa(2-). In both M(Umpa) series deprotonation of the uracil residue leads to the formation of M(Umpa-H)(-) complexes at higher pH values. Their stability was evaluated by taking into account the fact that the uracilate residue can bind metal ions to give M(2)(Umpa-H)(+) species. This has led to two further important insights: 1) In M(6Umpa-H)-cl the H(+) is released from (N1)H, giving rise to six-membered chelates (degrees of formation of ca. 90 to 99.9 % with Mn(2+), Co(2+), Cu(2+), Zn(2+), or Cd(2+)). 2) In M(5Umpa-H)$-cl the (N3)H is deprotonated, leading to a higher stability of the seven-membered chelates involving (C4)O (even Mg(2+) and Ca(2+) chelates are formed up to approximately 50 %). In both instances the M(Umpa-H)-op species led to the formation of M(2)(Umpa-H)(+) complexes that have one M(2+) at the phosphonate and one at the (N3)(-) (plus carbonyl) site; this proves that nucleotides can bind metal ions independently at the phosphate and the nucleobase residues. X-ray structural analyses of 6Umpa derivatives show that in diesters the phosphonate group is turned away from the uracil residue, whereas in H(2)(6Umpa) the orientation is such that upon deprotonation in aqueous solution a strong hydrogen bond is formed between (N1)H and PO(3) (2-); replacement of the hydro gen with M(2+) gives the M(6Umpa-H)-cl chelates mentioned.     

Stabilities and isomeric equilibria in aqueous solution of monomeric metal ion complexes of adenosine 5'-diphosphate (ADP3-) in comparison with those of adenosine 5'-monophosphate (AMP2-)

Under experimental conditions in which the self-association of the adenine phosphates (AP), that is, of adenosine 5'-monophosphate (AMP(2-)) and adenosine 5'-diphosphate (ADP(3-)), is negligible, potentiometric pH titrations were carried out to determine the stabilities of the M(H;AP) and M(AP) complexes where M(2+)=Mg(2+), Ca(2+), Sr(2+), Ba(2+), Mn(2+), Co(2+), Ni(2+), Cu(2+), Zn(2+), or Cd(2+) (25 degrees C; I=0.1 M, NaNO(3)). It is concluded that in the M(H;AMP)(+) species M(2+) is bound at the adenine moiety and in the M(H;ADP) complexes at the diphosphate unit; however, the proton resides in both types of monoprotonated complexes at the phosphate residue. The stabilities of nearly all the M(AMP) and M(ADP)(-) complexes are significantly larger than what is expected for a sole coordination of M(2+) to the phosphate residue. This increased complex stability is attributed, in agreement with previous (1)H NMR shift studies and further information existing in the literature, to the formation of macrochelates of the phosphate-coordinated metal ions with N7 of the adenine residues. On the basis of recent measurements with simple phosphate monoesters and phosphonate ligands (R-MP(2-)) as well as with diphosphate monoesters (R-DP(3-)), where R is a noncoordinating and noninhibiting residue, the increased stabilities of the M(AMP) and M(ADP)(-) complexes due to the M(2+)-N7 interaction could be evaluated and the extent of macrochelate formation calculated. The results show that the formation degrees of the macrochelates for the complexes of the alkaline earth ions are small (about 15 % at the most), whereas for the 3d metal ions as well as for Zn(2+) and Cd(2+) the formation degrees vary between about 15 % (Mn(2+)) and 75 % (Ni(2+)) with values of about 40 and 50 % for Zn(2+) and Cu(2+), respectively. It is interesting to note, taking earlier results for M(ATP)(2-) complexes also into account (ATP(4-)=adenosine 5'-triphosphate), that for a given metal ion in nearly all instances the formation degrees of the macrochelates are within the error limits the same for M(AMP), M(ADP)(-) and M(ATP)(2-) complexes; except for Co(2+) and Ni(2+) it holds M(AMP) > M(ADP)(-) approximately M(ATP)(2-). This result is astonishing if one considers that the absolute stability constants of these complexes, which are determined largely by the affinity of the phosphate residues, can differ by more than two orders of magnitude. The impact and conclusions of these observations for biological systems are shortly lined out.     

ChemInform Abstract: Analysis of Electronic Structures and Chemical Bonding of Metal‐Rich Compounds. Part 2. Presence of Dimer (T—T)4‐ and Isolated T2‐ Anions in the Polar Intermetallic Cr5B3‐Type Compounds AE5T3 (AE: Ca,Sr; T: Au,Ag, Hg,Cd, Zn).

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.     

Baeyer-villiger oxidation and oxidative cascade reactions with aqueous hydrogen peroxide catalyzed by lipophilic li[b(c(6) f(5) )(4) ] and ca[b(c(6) f(5) )(4) ](2)

Efficient and selective: Two lipophilic catalysts were used for Baeyer-Villiger (BV) oxidations to give lactones in high yields. Cascade reactions involving this BV oxidation were used to selectively obtain either unsaturated carboxylic acids or hydroxylactones in high yields from β-silyl cyclohexanones.     

Primary Fragmentation Pathways of Gas Phase [M(Uracil−H)(Uracil)]+ Complexes (M=Zn,Cu, Ni,Co, Fe,Mn, Cd,Pd , Mg,Ca, Sr,Ba, and Pb): Loss of Uracil versus HNCO

Complexes formed between metal dications, the conjugate base of uracil, and uracil are investigated by sustained off‐resonance irradiation collision‐induced dissociation (SORI‐CID) in a Fourier transform ion cyclotron resonance (FTICR) mass spectrometer. Positive‐ion electrospray spectra show that [M(Ura?H)(Ura)]⁺ (M=Zn, Cu, Ni, Co, Fe, Mn, Cd, Pd, Mg, Ca, Sr, Ba, or Pb) is the most abundant ion even at low concentrations of uracil. SORI‐CID experiments show that the main primary decomposition pathway for all [M(Ura?H)(Ura)]⁺, except where M=Ca, Sr, Ba, or Pb, is the loss of HNCO. Under the same SORI‐CID conditions, when M is Ca, Sr, Ba, or Pb, [M(Ura?H)(Ura)]⁺ are shown to lose a molecule of uracil. Similar results were observed under infrared multiple‐photon dissociation excitation conditions, except that [Ca(Ura?H)(Ura)]⁺ was found to lose HNCO as the primary fragmentation product. The binding energies between neutral uracil and [M(Ura?H)]⁺ (M=Zn, Cu, Ni, Fe, Cd, Pd ,Mg, Ca, Sr Ba, or Pb) are calculated by means of electronic‐structure calculations. The differences in the uracil binding energies between complexes which lose uracil and those which lose HNCO are consistent with the experimentally observed differences in fragmentation pathways. A size dependence in the binding energies suggests that the interaction between uracil and [M(Ura?H)]⁺ is ion–dipole complexation and the experimental evidence presented supports this.     

Enhanced Anion Binding from Unusual Coordination Modes of Bis(thiourea) Ligands in Platinum Group Metal Complexes

Treatment of a range of bis(thiourea) ligands with inert organometallic transition‐metal ions gives a number of novel complexes that exhibit unusual ligand binding modes and significantly enhanced anion binding ability. The ruthenium(II) complex [Ru(η⁶‐p‐cymene)(κS,S′,N‐ L³ ?H)]⁺ ( 2 b ) possesses juxtaposed four‐ and seven‐membered chelate rings and binds anions as both 1:1 and 2:1 host guest complexes. The pyridyl bis(thiourea) complex [Ru(η⁶‐p‐cymeme)(κS,S′,N_py‐ L⁴ )]²⁺ ( 4 ) binds anions in both 1:1 and 1:2 species, whereas the free ligand is ineffective because of intramolecular NH???N hydrogen bonding. Novel palladium(II) complexes with nine‐ and ten‐membered chelate rings are also reported.     

X-ray and solution structures of Cu(II) GHK and Cu(II) DAHK complexes: influence on their redox properties

The Gly‐His‐Lys (GHK) peptide and the Asp‐Ala‐His‐Lys (DAHK) sequences are naturally occurring high‐affinity copper(II) chelators found in the blood plasma and are hence of biological interest. A structural study of the copper complexes of these peptides was conducted in the solid state and in solution by determining their X‐ray structures, and by using a large range of spectroscopies, including EPR and HYSCORE (hyperfine sub‐level correlation), X‐ray absorption and ¹H and ¹³C NMR spectroscopy. The results indicate that the structures of [Cu^II(DAHK)] in the solid state and in solution are similar and confirm the equatorial coordination sphere of NH₂, two amidyl N and one imidazole N. Additionally, a water molecule is bound apically to Cu^II as revealed by the X‐ray structure. As reported previously in the literature, [Cu^II(GHK)], which exhibits a dimeric structure in the solid state, forms a monomeric complex in solution with three nitrogen ligands: NH₂, amidyl and imidazole. The fourth equatorial site is occupied by a labile oxygen atom from a carboxylate ligand in the solid state. We probe that fourth position and study ternary complexes of [Cu^II(GHK)] with glycine or histidine. The Cu^II exchange reaction between different DAHK peptides is very slow, in contrast to [Cu^II(GHK)], in which the fast exchange was attributed to the presence of a [Cu^II(GHK)₂] complex. The redox properties of [Cu^II(GHK)] and [Cu^II(DAHK)] were investigated by cyclic voltammetry and by measuring the ascorbate oxidation in the presence of molecular oxygen. The measurements indicate that both Cu^II complexes are inert under moderate redox potentials. In contrast to [Cu^II(DAHK)], [Cu^II(GHK)] could be reduced to Cu^I around ?0.62 V (versus AgCl/Ag) with subsequent release of the Cu ion. These complete analyses of structure and redox activity of those complexes gave new insights with biological impact and can serve as models for other more complicated Cu^II–peptide interactions.     

Stability and structure of mixed-ligand metal ion complexes that contain Ni2+, Cu2+, or Zn2+, and Histamine, as well as adenosine 5'-triphosphate (ATP4-) or uridine 5'-triphosphate (UTP(4-): an intricate network of equilibria

With a view on protein–nucleic acid interactions in the presence of metal ions we studied the “simple” mixed‐ligand model systems containing histamine (Ha), the metal ions Ni²⁺, Cu²⁺, or Zn²⁺ (M²⁺), and the nucleotides adenosine 5′‐triphosphate (ATP^4?) or uridine 5′‐triphosphate (UTP^4?), which will both be referred to as nucleoside 5′‐triphosphate (NTP^4?) . The stability constants of the ternary M(NTP)(Ha)^2? complexes were determined in aqueous solution by potentiometric pH titrations. We show for both ternary‐complex types, M(ATP)(Ha)^2? and M(UTP)(Ha)^2?, that intramolecular stacking between the nucleobase and the imidazole residue occurs and that the stacking intensity is approximately the same for a given M²⁺ in both types of complexes: The formation degree of the intramolecular stacks is estimated to be 20 to 50 %. Consequently, in protein–nucleic acid interactions imidazole–nucleobase stacks may well be of relevance. Furthermore, the well‐known formation of macrochelates in binary M²⁺ complexes of purine nucleotides, that is, the phosphate‐coordinated M²⁺ interacts with N7, is confirmed for the M(ATP)^2? complexes. It is concluded that upon formation of the mixed‐ligand complexes the M²⁺? N7 bond is broken and the energy needed for this process corresponds to the stability differences determined for the M(UTP)(Ha)^2? and M(ATP)(Ha)^2? complexes. It is, therefore, possible to calculate from these stability differences of the ternary complexes the formation degrees of the binary macrochelates: The closed forms amount to (65±10) %, (75±8) %, and (31±14) % for Ni(ATP)^2?, Cu(ATP)^2?, and Zn(ATP)^2?, respectively, and these percentages agree excellently with previous results obtained by different methods, confirming thus the internal validity of the data and the arguments used in the evaluation processes. Based on the overall results it is suggested that M(ATP)^2? species, when bound to an enzyme, may exist in a closed macrochelated form only, if no enzyme groups coordinate directly to the metal ion.     

Structure and Bonding in BAlH5 (B: Be,Ca, Sr) from First‐Principle Calculations.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.     

Acid-base and metal-ion-binding properties of 9-[2-(2-phosphonoethoxy)ethyl]adenine (PEEA), a relative of the antiviral nucleotide analogue 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA). An exercise on the quantification of isomeric complex equilibria in solution

The acidity constants of 3-fold protonated 9-[2-(2-phosphonoethoxy)ethyl]adenine, H3(PEEA)+, and of 2-fold protonated (2-phosphonoethoxy)ethane, H2(PEE), and the stability constants of the M(H;PEEA)+, M(PEEA), and M(PEE) complexes with M2+ = Mg2+, Ca2+, Sr2+, Ba2+, Mn2+, Co2+, Ni2+, Cu2+, Zn2+, or Cd2+ have been determined (potentiometric pH titrations; aqueous solution; 25 degrees C; I = 0.1 M, NaNO3). It is concluded that in the M(H;PEEA)+ species, the proton is at the phosphonate group and the metal ion at the adenine residue. The application of previously determined straight-line plots of log K(M(R-PO3))M versus pK(H(R-PO3))H for simple phosph(on)ate ligands, R-PO3(2-), where R represents a residue that does not affect metal-ion binding, proves that the M(PEEA) complexes of Co2+, Ni2+, Cu2+, Zn2+, and Cd2+ as well as the M(PEE) complexes of Co2+, Cu2+, and Zn2+ have larger stabilities than is expected for a sole phosphonate coordination of M2+. For the M2+ complexes without an enhanced stability (e.g., Mg2+ or Mn2+), it is concluded that M2+ binds in a monodentate fashion to the phosphonate group of the two ligands. Combination of all of the results allows the following conclusions: (i) The increased stability of the Co(PEE), Cu(PEE), Zn(PEE), and Co(PEEA) complexes is due to the formation of six-membered chelates involving the ether-oxygen atom of the aliphatic residue (-CH2-O-CH2CH2-PO3(2-)) of the ligands with formation degrees of about 15-30%. (ii) Cd(PEEA) forms a macrochelate with N7 of the adenine residue (formation degree about 30%); Ni(PEEA) has similar properties. (iii) With Zn(PEEA), both mentioned types of chelates are observed, that is, Zn(PEEA)(cl/O) and Zn(PEEA)(cl/N7), with formation degrees of about 13 and 41%, respectively; the remaining 46% is due to the "open" isomer Zn(PEEA)(op) in which the metal ion binds only to the PO3(2-) group. (iv) Most remarkable is Cu(PEEA) because a fourth isomer, Cu(PEEA)(cl/O/N3), is formed that contains a six-membered ring involving the ether oxygen next to the phosphonate group and also a seven-membered ring involving N3 of the adenine residue with a very significant formation degree of about 50%. Hence, PEEA(2-) is a truly ambivalent ligand, its properties being strongly dependent on the kind of metal ion involved. Comparisons with M2+ complexes formed by the dianions of 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA) and related ligands reveal that five-membered chelates involving an ether-oxygen atom are considerably more stable than the corresponding six-membered ones. This observation offers an explanation of why PMEA is a nucleotide analogue with excellent antiviral properties and PEEA is not.     

Complexes of copper(II) with adenosine or guanosine nucleosides, nucleotides 5'-monophosphate, 2'-deoxynucleosides or 2'-deoxynucleotides 5'-monophosphate in aqueous solution

In this paper copper(II) complex formation in aqueous solution with a series of nucleosides (adenosine or guanosine) or nucleotides 5'-monophosphate is studied by means of potentiometry, visible spectrophotometry and ultraviolet circular dichroism. A chemical model has been formulated for each binary system (at T= 25 degrees C and I = 0.1 M), with particular attention to the interaction in the basic field. A spectrum (both visible absorption and ultraviolet circular dichroism) for each complex with a significant percentage of formation (in the adopted experimental conditions) has been calculated, allowing structural details to be hypothesised. The interaction with deprotonated alcoholic group(s) of the ribose moiety has been found to be fundamental in determining the co-ordination chemistry of each ligand considered while cases of co-operation between the purine and ribose donor(s) were also considered. Confirmations were also obtained by an investigation on the corresponding 2'-deoxy compounds as ligands.     

Charge transfer complexes of adenosine-5'-monophosphate and cytidine-5'-monophosphate with water-soluble cobalt(II) Schiff base complexes in aqueous solution

Water-soluble cobalt(II) tetradentate Schiff base complexes have been shown to form charge transfer (CT) complexes with a series of nucleoside monophosphates including adenosine-5'-monophosphate (AMP) and cytidine-5'-monophosphate (CMP). The investigated water-soluble cobalt(II) Schiff base complexes are (i) disodium[{bis(5-sulfo-salicylaldehyde)-o-phenylenediiminato}cobalt(II)], Na2[Co(SO3-salophen)] (1); (ii) disodium[{bis(5-sulfo-salicylaldehyde)-4,5-dimethyl-o-phenylenediiminato}cobalt(II)], Na2[Co(SO3-sal-4,5-dmophen)] (2) and (iii) disodium[{bis(4-methoxy-5-sulfo-salicylaldehyde)-4,5-dimethyl-o-phenylenediiminato}cobalt(II)], Na(2)[Co(SO3-4-meosal-4,5-dmophen)] (3). The formation constant and thermodynamic parameters for charge transfer complex formation of water-soluble cobalt(II) Schiff base complexes with nucleoside monophosphates were determined spectrophotometrically in aqueous solution at constant ionic strength (I = 0.2 mol dm(-3) KNO3) under physiological condition (pH 7.0) and at various temperatures between 288 and 308 K. The stoichiometry has been found to be 1:1 (water-soluble cobalt(II) Schiff base complex: nucleoside monophosphate) in each case. Our spectroscopic and thermodynamic results show that the interaction of water-soluble cobalt(II) Schiff base complexes with the investigated nucleoside monophosphates occurs mainly through the phosphate group. The trend of the interaction according to the cobalt(II) Schiff base complexes due to electronic and steric factors is as follows: Na2[Co(SO3-salophen)] > Na2[Co(SO3-sal-4,5-dmophen)] > Na2[Co(SO3-4-meosal-4,5-dmophen)]. Also the trend of the interaction of a given cobalt(II) Schiff base complex according to the nucleoside monophosphate is as follows: CMP > AMP.     

ChemInform Abstract: [Ta3O3]A (A: Li,Na, K) and [Ta3O3]B[Ta3O3] (B: Ca,Sr, Ba): Sandwich‐Type Complexes Containing Ta3O3‐ δ and π Double Aromatic Ligands.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.     

Inosylyl(3'-->5')inosine (IpI-). Acid-base and metal ion-binding properties of a dinucleoside monophosphate in aqueous solution

The acidity constants of the (N7)H(+) sites of inosylyl(3'-->5')inosine (IpI(-)) were estimated and those of its (N1)H sites were measured by potentiometric pH titrations in aqueous solution (25 degrees C; I = 0.1 M, NaNO3). The same method was used for the determination of the stability constants of the 1:1 complexes formed between Mg(2+), Co(2+), Ni(2+), Zn(2+), or Cd(2+) (= M(2+)) and (IpI - H)(2-) and, in the case of Mg(2+), also of (IpI - 2H)(3-). The stability constants of the M(IpI)(+) complexes were estimated. The acidity constants of H(inosine)(+) and the stability constants of the M(Ino)(2+) and M(Ino - H)(+) complexes were taken from the literature. The comparison of these and related data allows the conclusion that, in the M(IpI - H) species, chelates are formed; most likely they are preferably of an N7/N7 type. For the metal ions Co(2+), Ni(2+), Zn(2+), or Cd(2+), the formation degrees of the chelates are on the order of 60-80%; no chelates could be detected for the Mg(IpI - H) complexes. It is noteworthy that the (N1)H deprotonation, which leads to the M(IpI - H) species, occurs in all M(IpI)(+) complexes in the physiological pH range of about 7.5 or even below.     

A Bioinorganic View of Alzheimer’s Disease: When Misplaced Metal Ions (Re)direct the Electrons to the Wrong Target

Metal ions Cu, Zn and Fe, seem to play a pivotal role in Alzheimer’s disease and other neurodegenerative diseases. In order to understand this in a broader sense, one has to considerer the peculiarities of metal metabolism in the brain compared to most other tissues, as well as the importance of the redox active metal ions, Fe and Cu, in oxygen metabolism and the connected oxidative stress.