Acid-base and metal-ion-binding properties of xanthosine 5'-monophosphate (XMP) in aqueous solution: complex stabilities, isomeric equilibria, and extent of macrochelation

The four acidity constants of threefold protonated xanthosine 5'-monophosphate, H3(XMP)+, reveal that at the physiological pH of 7.5 (XMP-H)(3-) strongly dominates (and not XMP(2-) as given in textbooks); this is in contrast to the related inosine (IMP(2-)) and guanosine 5'-monophosphate (GMP(2-)) and it means that XMP should better be named as xanthosinate 5'-monophosphate. In addition, evidence is provided for a tautomeric (XMP-HN1)(3-)/(XMP-HN3)(3-) equilibrium. The stability constants of the M(H;XMP)+ species were estimated and those of the M(XMP) and M(XMP-H)- complexes (M2+=Mg2+, Ca2+, Sr2+, Ba2+, Mn2+, Co2+, Ni2+, Cu2+, Zn2+, Cd2+) measured potentiometrically in aqueous solution. The primary M2+ binding site in M(XMP) is (mostly) N7 of the monodeprotonated xanthine residue, the proton being at the phosphate group. The corresponding macrochelates involving P(O)2(OH)- (most likely outer-sphere) are formed to approximately 65% for nearly all M2+. In M(XMP-H)- the primary M2+ binding site is (mostly) the phosphate group; here the formation degree of the N7 macrochelates varies widely from close to zero for the alkaline earth ions, to approximately 50% for Mn2+, and approximately 90% or more for Co2+, Ni2+, Cu2+, Zn2+, and Cd2+. Because for (XMP-H)(3-) the micro stability constants quantifying the M2+ affinity of the xanthosinate and PO3(2-) residues are known, one may apply a recently developed quantification method for the chelate effect to the corresponding macrochelates; this chelate effect is close to zero for the alkaline earth ions and it amounts to about one log unit for Co2+, Ni2+, Cu2+. This method also allows calculation of the formation degrees of the monodentatally coordinated isomers; this information is of relevance for biological systems because it demonstrates how metal ions can switch from one site to another through macrochelate formation. These insights are meaningful for metal-ion-dependent reactions of XMP in metabolic pathways; previous mechanistic proposals based on XMP(2-) need revision.     

Evidence for intramolecular aromatic-ring stacking in the physiological pH range of the monodeprotonated xanthine residue in mixed-ligand complexes containing xanthosinate 5'-monophosphate (XMP)

The stability constants of the mixed-ligand complexes formed between Cu(Arm)2+ [Arm = 2,2'-bipyridine (Bpy) or 1,10-phenanthroline (Phen)], and the di- or trianion of xanthosine 5'-monophosphoric acid [= XMP(2-) or (XMP - H)(3-)] were determined by potentiometric pH titration in aqueous solution (25 degrees C; I = 0.1 M, NaNO3). Those for the monoanion, i.e., the Cu(Arm)(H;XMP)+ complexes, could only be estimated; for these species it is concluded that the metal ion is overwhelmingly bound at N7 and the proton resides at the phosphate group. Similarly, in the Cu(Arm)(XMP)+/- [= Cu(Arm)(X - H.MP.H)+/-] complexes Cu(Arm)2+ is also at N7 but the xanthine residue has lost a proton whereas the phosphate group still carries one, i.e., stacking plays, if at all, only a very minor role, yet, the N7-bound Cu(Arm)2+ appears to form an outer-sphere macrochelate with P(O)2(OH)-, its formation degree being about 60%. All this is different in the Cu(Arm)(XMP - H)- complexes, which are formed by the (XMP - H)(3-) species, that occur at the physiological pH of 7.5 and for which previously evidence has been provided that in a tautomeric equilibrium the xanthine moiety loses a proton either from (N1)H or (N3)H. In Cu(Arm)(XMP - H)- the phosphate group is the primary binding site for Cu(Arm)2+ and the observed increased complex stability is mainly due to intramolecular stack (st) formation between the aromatic-ring systems of Phen or Bpy and the monodeprotonated xanthine residue of (XMP - H)(3-); e.g., the stacked Cu(Phen)(XMP - H) isomer occurs with approximately 76%. Regarding biological systems the most important result is that at physiological pH the xanthine moiety has lost a proton from the (N1)H/(N3)H sites forming (XMP - H)(3-) and that its anionic xanthinate residue is able to undergo aromatic-ring stacking.     

Understanding the acid-base properties of adenosine: the intrinsic basicities of N1, N3 and N7

Adenosine (Ado) can accept three protons, at N1, N3, and N7, to give H(3) (Ado)(3+) , and thus has three macro acidity constants. Unfortunately, these constants do not reflect the real basicity of the N sites due to internal repulsions, for example, between (N1)H(+) and (N7)H(+). However, these macroconstants are still needed for the evaluations and the first two are taken from our own earlier work, that is, pK(H)(H(3))((Ado)) = -4.02 and pK(H)(H(2))((Ado)) = -1.53; the third one was re-measured as pK(H)(H)((Ado)) = 3.64 ± 0.02 (25 °C; I=0.5 M, NaNO(3)), because it is the main basis for evaluating the intrinsic basicities of N7 and N3. Previously, contradicting results had been published for the micro acidity constant of the (N7)H(+) site; this constant has now been determined in an unequivocal manner, and that of the (N3)H(+) site was obtained for the first time. The micro acidity constants, which describe the release of a proton from an (N)H(+) site under conditions for which the other nitrogen atoms are free and do not carry a proton, decrease in the order pk(N7-N1)(N7(Ado)N1·H)) = 3.63 ± 0.02 > pk(N7-N1)(H·N7(Ado)N1) = 2.15 ± 0.15 > pk(N3-N1,N7)(H·N3(Ado)N1,N7) =1.5 ± 0.3, reflecting the decreasing basicity of the various nitrogen atoms, that is, N1>N7>N3. Application of the above-mentioned microconstants allows one to calculate the percentages (formation degrees) of the tautomers formed for monoprotonated adenosine, H(Ado)(+) , in aqueous solution; the results are 96.1, 3.2, and 0.7% for N7(Ado)N1·H(+), (+)H·N7(Ado)N1, and (+)H·N3(Ado)N1,N7, respectively. These results are in excellent agreement with theoretical DFT calculations. Evidently, H(Ado)(+) exists to the largest part as N7(Ado)N1·H(+) having the proton located at N1; the two other tautomers are minority species, but they still form. These results are not only meaningful for adenosine itself, but are also of relevance for nucleic acids and adenine nucleotides, as they help to understand their metal ion-binding properties; these aspects are briefly discussed.     

New members of a class of dinitrosyliron complexes (DNICs): interconversion and spectroscopic discrimination of the anionic {Fe(NO)2}9 [(NO)2Fe(C3H3N2)2]- and [(NO)2Fe(C3H3N2)(SR)]- (C3H3N2 = deprotonated imidazole; R = tBu, Et, Ph)

The anionic {Fe(NO)2}(9) DNIC[(NO)2Fe(C3H3N2)2](-) (2) (C3H3N2 = deprotonated imidazole) containing the deprotonated imidazole-coordinated ligands and DNICs [(NO)2Fe(C3H3N2)(SR)](-) (R = (t)Bu(3), Et(4), Ph(5)) containing the mixed deprotonated imidazole-thiolate coordinated ligands, respectively, were synthesized by thiol protonation or thiolate(s) ligand-exchange reaction. The anionic {Fe(NO)2}(9) DNICs 2- 5 were characterized by IR, UV-vis, EPR, and single-crystal X-ray diffraction. The facile transformation among the anionic {Fe(NO)2}(9) DNICs 2- 5 and [(NO)2Fe(S(t)Bu)2](-)/[(NO)2Fe(SEt)2](-)/[(NO)2Fe(SPh)2](-) was demonstrated in this systematic study. Of importance, the distinct electron-donating ability of thiolates serve to regulate the stability of the anionic {Fe(NO)2}(9) DNICs and the ligand-substitution reactions of DNICs. At 298 K, DNIC 2 exhibits the nine-line EPR signal with g = 2.027 (aN(NO) = 2.20 and aN(Im-H) = 3.15 G; Im-H = deprotonated imidazole) and DNIC 3 displays the nine-line signals with g = 2.027 (aN(NO) = 2.35 and aN(Im-H) = 4.10 G). Interestingly, the EPR spectrum of complex 4 exhibits a well-resolved 11-line pattern with g = 2.027 (aN(NO) = 2.50, aN(Im-H) = 4.10 G, and aH = 1.55 G) at 298 K. The EPR spectra (the pattern of hyperfine splitting) in combination with IR nu NO spectra (DeltanuNO = the separation of NO stretching frequencies, DeltanuNO = approximately 62 cm (-1) for 2 vs approximately 50 cm(-1) for 3- 5 vs approximately 43 cm(-1) for [(NO)2Fe(S(t)Bu)2](-)/[(NO)2Fe(SEt)2](-)/[(NO)2Fe(SPh)2](-)) may serve as an efficient tool for the discrimination of the existence of the anionic {Fe(NO)2}(9) DNICs containing the different ligations [N,N]/[N,S]/[S,S].     

Synthesis and acid-base properties of (1H-benzimidazol-2-yl-methyl)phosphonate (Bimp2-). Evidence for intramolecular hydrogen-bond formation in aqueous solution between (N-1)H and the phosphonate group

The synthesis of (1H-benzimidazol-2-yl-methyl)phosphonic acid, H2(Bimp)+/-, is described: 2-chloromethylbenzimidazole was reacted with ethylchloroformate to give 1-carboethoxy-2-chloromethylbenzimidazole which was treated with trimethyl phosphite and after hydrolysis with aqueous HBr H2(Bimp)+/- was obtained. In H2(Bimp)+/- one proton is at the N-3 site and the other at the phosphonate group; both acidity constants were determined in aqueous solution by potentiometric pH titrations (25 degrees C; I = 0.1 M, NaNO3) and this furnished the pKa values of 5.37 +/- 0.02 and 7.41 +/- 0.02, respectively. The acidity constant for the release of the primary proton from the P(O)(OH)2 group of H3(Bimp)+ was estimated: pKa = 1.5 +/- 0.2. Moreover, Bimp2- can be further deprotonated at its neutral (N-1/N-3)H site to give the benzimidazolate residue, but this reaction occurs only in strongly alkaline solution (KOH); application of the H_ scale developed by G. Yagil (J. Phys. Chem., 1967, 71, 1034) together with UV spectrophotometric measurements gave pKa = 14.65 +/- 0.12. Comparisons with acidity constants taken from the literature show that this latter pKa value is far too large and this allows the conclusion that an intramolecular hydrogen bond is formed between the (N-1/N-3)H site and the phosphonate group of Bimp2-; the formation degree of this hydrogen-bonded isomer is estimated to be 98 +/- 2%. The general relevance of this and the other results are shortly discussed and the species distribution for the Bimp system in dependence on pH is provided.     

On the Origin of the Enhanced Acidity of Chalcocyclopentadienes (Cyclopentadiene Chalcogenols) in the Gas Phase

The intrinsic acidity of chalcocyclopentadienes (CpXH; X=O, S, Se, Te) is investigated by high‐level G3B3 and G2 ab initio as well as B3LYP DFT calculations, which show that, independent of the nature of the heteroatom, all chalcocyclopentadienes are stronger acids in the gas phase than cyclopentadiene. However the acidity does not increase regularly down the group, and the acidity enhancement for Te derivatives is five times larger than for O derivatives, but only twice that of S‐containing compounds. The most favorable deprotonation process corresponds to loss of the proton attached to the heteroatom, with the sole exception of the 5‐substituted 1,3‐cyclopentadienes, for which the O and S derivatives are predicted to behave as carbon acids. No matter the nature of the heteroatom, the 1‐substituted 1,3‐cyclopentadienes are the strongest acids. The intrinsic acidity of all isomers, namely, 1‐substituted, 2‐substituted, and 5‐substituted 1,3‐cyclopentadienes, increases with increasing aromaticity of the anion formed on deprotonation, and therefore the Te compound is the strongest acid for the three series. However, the intrinsic acidity of chalcocyclopentadienes is not dictated by aromaticity, so that, in general, the most stable deprotonated species do not coincide with the most aromatic ones.     

N1 and N3 linkage isomers of neutral and deprotonated cytosine with trans-[(CH3NH2)2PtII

A series of complexes obtained from the reaction of trans-[(CH3NH2)2PtII] with unsubstituted cytosine (CH) and its anion (C), respectively, has been prepared and isolated or detected in solution: trans-[Pt(CH3NH2)2(CH-N3)Cl]Cl.H2O (1), trans-[Pt(CH3NH2)2(CH-N3)2](ClO4)2 (1a), trans-[Pt(CH3NH2)2(C-N3)2].2H2O (1b), trans-[Pt(CH3NH2)2(CH-N3)2](ClO4)(2).2DMSO (1c), trans-[Pt(CH3NH2)2(CH-N1)2] (NO3)(2).3H2O (2a), trans-[Pt(CH3NH2)2(C-N1)2].2H2O (2b), trans-[Pt(CH3NH2)2(CH-N1)(CH-N3)](ClO4)2 (3a), trans-[Pt(CH3NH2)2(C-N1)(C-N3)] (3b), and trans-[Pt(CH3NH2)2(N1-CN3)(N3-C-N1)Cu(OH)]ClO(4).1.2H2O (4). X-ray crystal structures of all these compounds, except 3a and 3b, are reported. Complex 2a is of particular interest in that it contains the rarer of the two 2-oxo-4-amino tautomer forms of cytosine, namely that with the N3 position protonated. Since the effect of PtII on the geometry of the nucleobase is minimal, bond lengths and angles of CH in 2a reflect, to a first approximation, those of the free rare tautomer. Compared to the preferred 2-oxo-4-amino tautomer (N1 site protonated) of CH, the rare tautomer in 2a differs particularly in internal ring angles (7-11 sigma). Formation of compounds containing the rare CH tautomers on a preparative scale can be achieved by a detour (reaction of PtII with the cytosine anion, followed by cytosine reprotonation) or by linkage isomerization (N3-->N1) under alkaline reaction conditions. Surprisingly, in water and over a wide pH range, N1 linkage isomers (3a, 2a) form in considerably higher amounts than can be expected on the basis of the tautomer equilibrium. This is particularly true for the pH range in which the cytosine is present as a neutral species and implies that complexation of the minor tautomer is considerably promoted. Deprotonation of the rare CH tautomers in 2a occurs with pKa values of 6.07 +/- 0.18 (1 sigma) and 7.09 +/- 0.11 (1 sigma). This value compares with pKa 9.06 +/- 0.09 (1 sigma) (average of both ligands) in 1a.     

Transition metal complexes coordinated by an NAD(P)H model compound and their enhanced hydride-donating abilities in the presence of a base

The ruthenium(II) and rhenium(I) complexes containing an NAD(P)H model compound, 1-benzyl-1,4-dihydronicotinamide (BNAH), as ligand, [Ru(tpy)(bpy)(BNAH)]2+ (1 a) and [Re(bpy)(CO)3(BNAH)]+ (1 b), were quantitatively produced by the reaction of the corresponding metal hydrido complexes with BNA(+) (1-benzylnicotinamidium cation). In the presence of base with pK(a) = 8.9, 1 a and 1 b have much greater reducing power than "free" BNAH. The oxidation potentials of 1 a in the absence and the presence of triethylamine were 0.55 V and -0.04 V, respectively, versus Ag/AgNO(3), whereas that of "free" BNAH was 0.30 V. Spectroscopic results clearly showed that the base extracts a proton from the carbamoyl group on 1 a and 1 b to give the deprotonated BNAH coordinating to the transition-metal complexes [Ru(tpy)(bpy)(BNAH-H+)]+ (3 a) and [Re(bpy)(CO)3(BNAH-H+)] (3 b); this deprotonation underlies the enhancement in reducing ability. The deprotonated forms 3 a and 3 b can efficiently reduce other NAD(P) models to give the corresponding 1,4-dihydro form, resulting in the deprotonated BNA+ being coordinated to the metal complexes [Ru(tpy)(bpy)(BNA(+)-H+)]2+ (2 a) and [Re(bpy)(CO)3(BNA+-H+)]+ (2 b); "free" BNAH and the protonated adducts 1 a and 1 b cannot act in this way. X-ray crystallography was performed on the PF6- salt of 2 a, and showed that the deprotonated nitrogen atom on the carbamoyl group coordinates to the ruthenium(II) metal center with a bond length of 2.086(3) Angstroms. Infrared spectral data suggested that the deprotonated carbamoyl group on the reduced forms 3 a and 3 b is converted to the imido group, and that the oxygen atom coordinates to the metal center.     

Intrinsic acid-base properties of purine derivatives in aqueous solution and comparison of the acidifying effects of platinum(II) coordinated to N1 or N7: acidifying effects are reciprocal and the proton "outruns" divalent metal ions

The effect of Pt(2+) coordination, in particular of (dien)Pt(2+) or cis-(NH(3))(2)Pt(2+), on the acid-base properties of the purine ligands 9-ethylguanine (9EtG), 9-methylhypoxanthine (9MeHx), inosine (Ino), 9-methyladenine (9MeA), and N6',N6',N9-trimethyladenine (TriMeA) is quantitatively evaluated. The corresponding acidity constants of the complexes are calculated by curve-fitting procedures using previously published (1)H NMR shift data which had been measured in aqueous solution (D(2)O) in dependence on pH (pD). Comparison of the pK(a) values of the ligands with those of the Pt(2+) complexes reveals the expected behavior for the (N7)-platinated complexes; i.e., the (N1)H(0/+) sites are acidified due to charge repulsion. However, Pt(2+) coordination at (N1)(-)(/0) sites leads to an (already previously observed) apparent increase in the basicity of the N7 sites for the guanine, hypoxanthine, and adenine residues; this is also the case if Pt(2+) is bound to N3. Coordination of Pt(2+) to both the (N1)(-) and N7 sites of 9EtG results apparently in an enhanced basicity of N3 if compared with the release of the proton from the (N3)H(+) site in H(2)(9EtG)(2+). For the former cases in aqueous solution (H(2)O) it is now proven for a comprehensive set of data (seven examples), by taking into account the intrinsic basicities of the various N7 sites via micro acidity constants, that the acidifications are reciprocal and identical. This means Pt(2+) coordinated to (N1)(-)(/0) sites in guanine, hypoxanthine, or adenine residues acidifies the (N7)H(+) unit to the same extent as (N7)-coordinated Pt(2+) acidifies the (N1)H(0/+) site. In other words, the apparently increased basicity of N7 upon Pt(2+) coordination at (N1)(-)(/0) sites disappears if the micro acidity constants of the appropriate isocharged tautomers of the ligand are properly taken into account. It is further proven, on the basis of the evaluations of the nucleotide analogue 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA), that these given conclusions are also valid for nucleotides. In addition, it is shown that the mentioned apparent basicity increase, which results from the use of macro acidity constants, has its origin in the fact that the proton-metal ion (Pt(2+)) interaction (the extent of which depends on the kind of metal ion involved) is less pronounced than the proton-proton interaction. Finally, the proven reciprocal behavior will now allow one to determine micro acidity constants of ligands by studying complexes formed with kinetically inert metal ions. A further result of interest is the proof that the competition of Pt(2+) (or Pd(2+)) with the proton for the (N1)(-) and N7 binding sites of inosinate results in the isomer where the metal ion is at N7 with the proton relegated to (N1)(-); this isomer is favored by a factor of about 2000 compared with the one having the metal ion at (N1)(-) and the proton at N7.     

High sensitivity to transmission of attenuation in the metal activating effect of platinum on sequential H-D exchange at the four C8 sites of inosines in tetrakis(inosine)platinum(II) chloride

Hydrogen-deuterium exchange of the carbon-bound C(8)-H protons of the inosine residues in tetrakis(inosine)platinum(ii) chloride, S, with Pt binding at N(7), was studied in aqueous buffer solutions at 60 degrees C by (1)H NMR spectroscopy. The kinetics at all four C(8) sites as a function of pD of the D(2)O/OD(-) medium was measured through the disappearance of the C(8)-H signal, which yielded the pseudo first-order rate constant for exchange, k(obs). Plots of k(obs)versus [OD(-)] showed curvature reminiscent of saturation type kinetics and indicative of competitive deprotonation of N(1)-H sites. In contrast, the analogous N(1)-methylated cis-bis(1-methylinosine)diammineplatinum(ii) chloride leads to a linear k(obs)versus [OD(-)] plot. The potentiometrically determined macroscopic composite N(1)-H ionization constant was further dissected into the successive microscopic N(1)-H acidity constants of the four inosine residues of the complex S. The k(obs) values were also deconvoluted into individual rate constants k(ex) (i.e.k(0), k(1), k(2), k(3) for exchange of the successively deprotonated inosine moieties, S, S(1), S(2), S(3), it being assumed that S(4) where all four inosine ligands are deprotonated at N(1) is unreactive ("immunized") to exchange. The k(ex) values show a progressive attenuation in Pt activation of H-D exchange along the series, k(0), k(1), k(2), k(3). The k(ex) data thus generated, together with the deconvoluted individual pK(a) values allow the construction of the plot, log k(ex) [C(8)-H] vs. pK(a) [N(H)-1]. Remarkably, this plot exhibits good linearity (R(2) = 0.99), which accords this as a linear free energy relationship (LFER). The large negative slope value (-2.3) of this LFER reflects the high sensitivity of transmission of electron density from the ionized N(1) via Pt and/or through space to the remaining C(8)-H sites. This is to our knowledge the first instance in which a LFER is generated through modulation of a structure in a single molecule. One can anticipate that this approach may lead to: (1) predicting N-H acidity; (2) C-H H-D exchange susceptibility in a range of metal-biomolecule complexes; (3) their carbon acidity.     

Perturbation of the NH2 pKa value of adenine in platinum(II) complexes: distinct stereochemical internucleobase effects

The degree of acidification of the exocyclic N6 amino group of the model nucleobase 9-methyladenine (9MeA) in relation to the number and site(s) of Pt(II) binding has been studied in detail. It is found that twofold Pt(II) binding to N1 and N7 lowers the pK(a) value from 16.7 in the free base to 12-8. The lowest pK(a) values are observed when the resulting N6H(-) amide group is intramolecularly stabilized by an H-bond donor such as the N6H(2) group of a suitably positioned second 9MeA ligand. Deprotonation of the N6 amino group facilitates Pt migration from N1 to N6, and subsequent reprotonation of the N1 position yields a twofold N7,N6-metalated form of the rare imino tautomer of 9MeA, which has a pK(a) value of 5.03. These findings demonstrate a principle that is of potential relevance to the topic of "shifted pK(a)" values of adenine nucleobases, which is believed to be important with regard to acid-base catalysis of RNAs at physiological pH values. The principle states that a nucleobase pK(a) value can be sufficiently lowered to reach near-neutral values and that the pK(a) value of the protonated base does not necessarily have to be increased to accomplish this effect.     

Acidity of adenine and adenine derivatives and biological implications. A computational and experimental gas-phase study

The gas-phase acidities of adenine, 9-ethyladenine, and 3-methyladenine have been investigated for the first time, using computational and experimental methods to provide an understanding of the intrinsic reactivity of adenine. Adenine is found to have two acidic sites, with the N9 site being 19 kcal mol(-1) more acidic than the N10 site; the bracketed acidities are 333 +/- 2 and 352 +/- 4 kcal mol(-1), respectively. Because measurement of the less acidic site can be problematic, we benchmarked the adenine N10 measurement by bracketing the acidity of 9-ethyladenine, which has the N9 site blocked and allows for exclusive measurement of the N10 site. The acidity of 9-ethyladenine brackets to 352 +/- 4 kcal mol(-1), comparable to that of the N10 site of the parent adenine. Calculations and experiments with 3-methyladenine, a harmful mutagenic nucleobase, uncovered the surprising result that the most commonly written tautomer of 3-methyladenine is not the most stable in the gas phase. We have found that the most stable tautomer is the "N10 tautomer" 10, as opposed to the imine tautomer 3. The bracketed acidity of 10 is 347 +/- 4 kcal mol(-1). Since 10 is not a viable species in DNA, 3 is a likely tautomer; calculations indicate that this form has an extremely high acidity (320-323 kcal mol(-1)). The biological implications of these results, particularly with respect to enzymes that cleave alkylated bases from DNA, are discussed.     

Thermodynamic and kinetic studies of H atom transfer from HMo(CO)3(eta(5)-C5H5) to Mo(N[t-Bu]Ar)3 and (PhCN)Mo(N[t-Bu]Ar)3: direct insertion of benzonitrile into the Mo-H bond of HMo(N[t-Bu]Ar)3 forming (Ph(H)C=N)Mo(N[t-Bu]Ar)3

Synthetic studies are reported that show that the reaction of either H2SnR2 (R = Ph, n-Bu) or HMo(CO)3(Cp) (1-H, Cp = eta(5)-C5H5) with Mo(N[t-Bu]Ar)3 (2, Ar = 3,5-C6H3Me2) produce HMo(N[t-Bu]Ar)3 (2-H). The benzonitrile adduct (PhCN)Mo(N[t-Bu]Ar)3 (2-NCPh) reacts rapidly with H2SnR2 or 1-H to produce the ketimide complex (Ph(H)C=N)Mo(N[t-Bu]Ar)3 (2-NC(H)Ph). The X-ray crystal structures of both 2-H and 2-NC(H)Ph are reported. The enthalpy of reaction of 1-H and 2 in toluene solution has been measured by solution calorimetry (DeltaH = -13.1 +/- 0.7 kcal mol(-1)) and used to estimate the Mo-H bond dissociation enthalpy (BDE) in 2-H as 62 kcal mol(-1). The enthalpy of reaction of 1-H and 2-NCPh in toluene solution was determined calorimetrically as DeltaH = -35.1 +/- 2.1 kcal mol(-1). This value combined with the enthalpy of hydrogenation of [Mo(CO)3(Cp)]2 (1(2)) gives an estimated value of 90 kcal mol(-1) for the BDE of the ketimide C-H of 2-NC(H)Ph. These data led to the prediction that formation of 2-NC(H)Ph via nitrile insertion into 2-H would be exothermic by approximately 36 kcal mol(-1), and this reaction was observed experimentally. Stopped flow kinetic studies of the rapid reaction of 1-H with 2-NCPh yielded DeltaH(double dagger) = 11.9 +/- 0.4 kcal mol(-1), DeltaS(double dagger) = -2.7 +/- 1.2 cal K(-1) mol(-1). Corresponding studies with DMo(CO)3(Cp) (1-D) showed a normal kinetic isotope effect with kH/kD approximately 1.6, DeltaH(double dagger) = 13.1 +/- 0.4 kcal mol(-1) and DeltaS(double dagger) = 1.1 +/- 1.6 cal K(-1) mol(-1). Spectroscopic studies of the much slower reaction of 1-H and 2 yielding 2-H and 1/2 1(2) showed generation of variable amounts of a complex proposed to be (Ar[t-Bu]N)3Mo-Mo(CO)3(Cp) (1-2). Complex 1-2 can also be formed in small equilibrium amounts by direct reaction of excess 2 and 1(2). The presence of 1-2 complicates the kinetic picture; however, in the presence of excess 2, the second-order rate constant for H atom transfer from 1-H has been measured: 0.09 +/- 0.01 M(-1) s(-1) at 1.3 degrees C and 0.26 +/- 0.04 M(-1) s(-1) at 17 degrees C. Study of the rate of reaction of 1-D yielded kH/kD = 1.00 +/- 0.05 consistent with an early transition state in which formation of the adduct (Ar[t-Bu]N)3Mo...HMo(CO)3(Cp) is rate limiting.     

Microspeciation in the copper(II)-L-histidylglycine system. An ESR study by the two-dimensional computer simulation method

Twelve ESR-active (and one inactive) copper(II) complexes of L-histidylglycine (HL) were characterized via their formation (micro)constants and ESR parameters obtained by two-dimensional ESR spectroscopic evaluation in aqueous solution. In strongly acidic media, the ligand is coordinated through its N-terminal donor groups: the complex [CuLH(2)](3+) involves monodentate imidazole binding, whereas [CuLH](2+) involves bidentate ligation through the amino and imidazole N atoms. This histamine-like bonding mode also predominates in the isomers of [CuL(2)], formed at ligand excess near pH 7: in the major 4N isomer, both ligands occupy two equatorial sites, while in the 3N isomer, the second dipeptide is coordinated equatorially by the amino and axially by the imidazole groups. At above pH 3-4, deprotonation of the peptide group also starts: in approximately 60% of the molecules of [CuL](+), the peptide group is deprotonated, while in the minor isomer histamine-like coordination occurs. At higher pH, the active dimer [Cu(2)L(2)H(-2)], the mixed hydroxo complexes (the inactive [Cu(2)L(2)H(-3)](-) and the active [CuLH(-2)](-)), and the bis complexes [CuL(2)H](+) and [CuL(2)H(-1)](-) all involve tridentate equatorial ligation of the backbone by the amino and deprotonated peptide N and the carboxylate O atoms. In the active dimer, the neutral imidazole groups form bridges between CuLH(-1) units. In [CuL(2)H](+), the second ligand is bound equatorially via its imidazole group; in [CuL(2)H(-1)](-), the L ligand occupies the fourth equatorial site and an axial site through its amino and imidazole N atoms, respectively.     

OH(3) (-) and O(2)H(5) (-) double Rydberg anions: predictions and comparisons with NH(4) (-) and N(2)H(7) (-)

A low barrier in the reaction pathway between the double Rydberg isomer of OH(3) (-) and a hydride-water complex indicates that the former species is more difficult to isolate and characterize through anion photoelectron spectroscopy than the well known double Rydberg anion (DRA), tetrahedral NH(4) (-). Electron propagator calculations of vertical electron detachment energies (VEDEs) and isosurface plots of the electron localization function disclose that the transition state's electronic structure more closely resembles that of the DRA than that of the hydride-water complex. Possible stabilization of the OH(3) (-) DRA through hydrogen bonding or ion-dipole interactions is examined through calculations on O(2)H(5) (-) species. Three O(2)H(5) (-) minima with H(-)(H(2)O)(2), hydrogen-bridged, and DRA-molecule structures resemble previously discovered N(2)H(7) (-) species and have well separated VEDEs that may be observable in anion photoelectron spectra.     

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.     

Pyridine N-alkylation by lithium, magnesium, and zinc alkyl reagents: synthetic, structural, and mechanistic studies on the bis(imino)pyridine system

The 2,6-bis(alpha-iminoalkyl)pyridines 2,6-[ArNC(CR(3))](2)C(5)H(3)N [R = H, D; Ar = 2,6-i-Pr(2)C(6)H(3) (DIPP), 2,6-Me(2)C(6)H(3) (DMP)] react with MeLi in Et(2)O to give a binary mixture of products: the pyridine N-methylated species 2,6-[ArNC(CR(3))](2)C(5)H(3)N(Me)Li(OEt(2)) and the deprotonated/dedeuterated species 2-[ArNC(CR(3))],6-[ArNC(=CR(2))]C(5)H(3)NLi(OEt(2)). For R = D, the product ratio is 2:1 in favor of the N-methylated product, while, for R = H, the deprotonated product is favored by 5:1, increasing to 8:1 in toluene solvent. Warming solutions of the N-methylated species leads to clean conversion to the thermodynamically preferred deprotonated species. Crossover experiments show that MeLi is re-formed and dissociates from the terdentate ligand before deprotonating the ketimine methyl unit. For MgR(2) (R = Et, i-Pr) and ZnR(2) (R = Et) reagents, N-alkylation products are formed exclusively, but derivatives containing bulky aryl substituents are found to undergo further rearrangement to 2-alkylated species, arising by migration of the alkyl group of the N-alkyl moiety to the adjacent ring carbon atom. The reversibility of the N-alkylation process has been probed using deuterio-labeled Mg alkyl reagents and mixed alkyl zinc species. A cationic zinc derivative is shown to undergo "reverse" alkyl migration, from the heterocycle nitrogen atom to the zinc center. EPR spectroscopy reveals a paramagnetic intermediate in which the unpaired electron is delocalized over the heterocycle and di-imine moieties of the ligand, indicating that the N-alkylation reactions proceed via single electron-transfer processes.     

Migration of a cis-(NH3)2PtII moiety along two adenine nucleobases, from N1 to N6, is markedly facilitated by additional PtII entities coordinated to N7

Adenine acidification as a consequence of simultaneous PtII binding to N1 and N7 facilitates deprotonation of the exocyclic N(6)H2 group and permits PtII migration from N1 to N6 under mild conditions. Starting from the trinuclear complex cis-[(NH3)2Pt(N1-9-MeA-N7)2{Pt(NH3)3)}2]6+ (3), stepwise migration of cis-(NH3)2PtII takes place in the alkaline aqueous solution to give initially cis-[(NH3)2Pt(N1-9-MeA-N7)(N6-9-MeA--N7){Pt(NH3)3}2]5+ (4) and eventually cis-[(NH3)2Pt(N6-9-MeA--N7)2{Pt(NH3)3}2]4+ (5) (with 9-MeA = neutral 9-methyladenine, 9-MeA- = 9-methyl-adenine monoanion, deprotonated at N6). The migration process has been studied by 1H NMR spectroscopy, and relevant acid-base equilibria have been determined. 5 has been crystallized as its nitrate salt and has been characterized by X-ray crystallography. The precursor of 3, [(NH3)3Pt (9-MeA-N7)]Cl2.2H2O (2) has likewise been studied by X-ray analysis.     

Thermal decomposition of Pr[(C_5H_8NS_2)_3(C_(12)H_8N_2)]

The thermal behavior of the complex Pr[(C5H8NS2)3(C12H8N2)] in a dry nitrogen flow was examined by TG-DTG analysis. The TG-DTG investigations indicated that Pr[(C5H8NS2)3-(C12H8N2)] was decomposed into Pr2S3 and deposited carbon in one step where Pr2S3 predominated in the final products. The results of non-isothermal kinetic calculations showed that the decomposition stage was the random nucleation and subsequent growth mechanism (n = 2/3), the corresponding apparent activation energy ?was 115.89 kJ·mol-1 and the pre-expo-nential constant ln[A/s] was 7.8697. The empirical kinetics model equation was proposed as/(α) =3/2(1-α)[-ln(1-α)]1/3.The X-ray powder diffraction patterns of the thermal decomposition products at 800℃under N2 atmosphere show that the product can be indexed to the cubic Pr2S3 phase. The transmission electron microscopy (TEM) of the final product reveals the particle appearance of a diameter within 40 nm. The experimental results show that the praseodymium sulfide nanocrystal can be prepared from thermal decomposition of Pr[(C5H8NS2)3(C12H8N2)].     

Synthesis and Structures of Sb[N(H)(C(6)H(2)(t)Bu(3))](3) and Bi[N(H)(C(6)H(2)(t)Bu(3))](3): Implications for the Steric Limits of Supermesityl Substitution

Syntheses and isolations of the tris(amino)stibine and tris(amino)bismuthine E[N(H)(C(6)H(2)(t)Bu(3))](3) (E = Sb, Bi) from ECl(3) and LiN(H)(C(6)H(2)(t)Bu(3)) are described, together with spectroscopic and structural characterization [crystal data for C(54)H(90)N(3)Sb, M = 903.04, space group P&onemacr;, a = 11.491(5) ?, b = 24.652(7) ?, c = 10.002(5) ?, alpha = 98.38(3) degrees, beta = 96.44(5) degrees, gamma = 77.25(3) degrees, V = 2724(2) ?(3), D(c) = 1.101 Mg/m(3), Z = 2, R = 0.0547; crystal data for C(54)H(90)BiN(3), M = 990.27, space group P&onemacr;, a = 11.511(5) ?, b = 24.785(15) ?, c = 9.981(5) ?, alpha = 98.06(5) degrees, beta = 96.50(4) degrees, gamma = 77.40(5) degrees, V = 2742(2) ?(3), D(c) = 1.200 Mg/m(3), Z = 2, R = 0.0619]. The compounds bear the "bulky" 2,4,6-tri-tert-butylphenyl substituent (known as supermesityl or Mes), and their formation is considered in the context of the same reactions for PCl(3) and AsCl(3), which have been previously shown to produce the aminoiminopnictine structures [N(H)(C(6)H(2)(t)Bu(3))]P=N(C(6)H(2)(t)Bu(3)) and [N(H)(C(6)H(2)(t)Bu(3))]As=N(C(6)H(2)(t)Bu(3)). The observations establish the limits of the steric control by the supermesityl substituent and provide qualitative support for the thermodynamic significance of substituent steric strain.