John P. Caradonna

Solution and solid state studies on the interactions of protonated cytosine salts. III. Interpyrimidine base stacking and asymmetric interbase hydrogen bonding in the structure of 1-methylcytosine hemihydroiodide hemihydrate

Abstract Structural and spectroscopic data are presented on the compound 1-methylcytosine hemihydroiodide hemihydrate. In the solid, a 1:1 triply hydrogenbonded complex consisting of one protonated and one neutral 1-methylcytosine base is observed. The hydrogen bonding in this complex is asymmetric, and the asymmetry in the interbase hydrogen bonding is stimulated, at least in part, by base stacking considerations. The hydrogen-bonded base pairs associate into dimers about a crystallographic center of symmetry; the base-base stacking mode is strong [mean stacking distance = 3.22A] and is such that the molecular overlap is between protonated and neutral 1-methylcytosine molecules. The asymmetric, interbase hydrogen bonding and the protonated over neutral base stacking mode coexist in a synergistic interrelationship which maximizes molecular association and crystal packing. Intermolecular hydrogen bonds involving the 1-methylcytosine bases, the water of crystallization and the iodide anion also contribute to the overall crystal stability. Infra-red and 1H nmr data are also presented.

Heterolytic Cleavage of Peroxide by a Diferrous Compound Generates Metal-Based Intermediates Identical to Those Observed with Reactions Utilizing Oxygen-Atom-Donor Molecules

Under cryogenic stopped-flow conditions, addition of 2-methyl-1-phenylprop-2-yl hydroperoxide (MPPH) to the diiron(II) compound, [Fe(2)(H(2)Hbamb)(2)(NMeIm)(2)] (1; NMeIm=N-methylimidazole; H(4)HBamb: 2,3-bis(2-hydroxybenzamido)dimethylbutane) results in heterolytic peroxide O-O bond cleavage, forming a high-valent species, 2. The UV/Vis spectrum of 2 and its kinetic behavior suggest parallel reactivity to that seen in the reaction of 1 with oxygen-atom-donor (OAD) molecules, which has been reported previously. Like the interaction with OAD molecules, the reaction of 1 with MPPH proceeds through a three step process, assigned to oxygen-atom transfer to the iron center to form a high-valent intermediate (2), ligand rearrangement of the metal complex, and, finally, decay to a diferric mu-oxo compound. Careful examination of the order of the reaction with MPPH reveals saturation behavior. This, coupled with the anomalous non-Arrhenius behavior of the first step of the reaction, indicates that there is a preequilibrium peroxide binding step prior to O-O bond cleavage. At higher temperatures, the addition of the base, proton sponge, results in a marked decrease in the rate of O-O bond cleavage to form 2; this is assigned as a peroxide deprotonation effect, indicating that the presence of protons is an important factor in the heterolytic cleavage of peroxide. This phenomenon has been observed in other iron-containing enzymes, the catalytic cycles of which include peroxide O-O bond cleavage.

Solution and Solid State Studies on the Interactions of Protonated Cytosine Salts. IV. Asymmetric Interbase Hydrogen Bonding and Interpyrimidine Base Stacking in Triply Hydrogen-Bonded Cytosine Complexes. Crystal and Molecular Structure of Bis[1-Methylcytosine, 1-Methylcytosinium] Hexafluorosilicate Dihydrate

Abstract The crystal and molecular structures of the complex bis(1-methylcytosine, 1-methylcytosinium) hexafluorosilicate dihydrate are reported. In the solid, a 1:1 triply hydrogen-bonded complex consisting of one protonated and one neutral 1-methylcytosine base is observed. The hydrogen bonding in the complex cation is asymmetric, and the asymmetry in the interbase hydrogen bonding is stimulated to a large part by base stacking. The observed infinite, helical array of stacked complexes, in which the base stacking is strong [mean stacking distance = 3.36A] is such that the molecular overlap is between protonated and neutral 1-methylcytosine bases. The asymmetric interbase hydrogen bonding and the protonated/neutral base stacking mode coexist in a synergistic interrelationship which maximizes the molecular and crystal forces. The results found in this study are compared with a variety of other systems in which asymmetrically hydrogen-bonded cytosine complexes are observed, and it is found that although base stacking is also a predominant feature of these complexes in the solid, the base stacking found in this study is different.

Chemical and Biological Studies of cis — Diamminedichloroplatinum (II) Binding to DNA

Over a decade has passed since the initial observation that neutral platinum amine coordination compounds with cis configuration of labile groups were effective chemotherapeutic agents.1 Subsequent studies built a strong case that DNA is the relevant biological target of these complexes.2,3 Substantial effort has therefore been directed towards defining and characterizing the interactions of cis-Pt(NH3)2Cl2 (cis-DDP) and the inactive trans-Pt(NH3)2Cl2 (trans-DDP),4 the structures of which are shown in Figure 1, with DNA at the molecular level.

Solution and solid state studies on the interactions of protonated cytosine salts. II. Interpyrimidine hydrogen bonding versus cation-anion stacking in the crystal structures of protonated 1-methylcytosine perchlorate and protonated 1-benzylcytosine nitrate

Abstract The structural properties of the salts protonated 1-methylcytosine perchlorate and protonated 1benzylcytosine nitrate are reported. In each of the salts, it has been definitively established that N(3) of the cytosine ring is the site of protonation. Cation-anion hydrogen-bonding interactions of the type seen in the hydrohalide salts of protonated, N(1)-substituted cytosine derivatives are also observed to some extent in these systems. In addition, the stability of both these salts depends on other factors. In particular, the interpyrimidine hydrogen bonding in the perchlorate salt is very strong and observed here for the first time. Cation-anion stacking forces in the nitrate salt are vital to the observed crystal packing.

Characterization of Water Coordination to Ferrous Nitrosyl Complexes with fac-N2O, cis-N2O2, and N2O3 Donor Ligands

Electron paramagnetic resonance (EPR) experiments were done on a series of S = (3)/2 ferrous nitrosyl model complexes prepared with chelating ligands that mimic the 2-His-1-carboxylate facial triad iron binding motif of the mononuclear nonheme iron oxidases. These complexes formed a comparative family, {FeNO}(7)(N2Ox)(H2O)3-x with x = 1-3, where the labile coordination sites for the binding of NO and solvent water were fac for x = 1 and cis for x = 2. The continuous-wave EPR spectra of these three complexes were typical of high-spin S = (3)/2 transition-metal ions with resonances near g = 4 and 2. Orientation-selective hyperfine sublevel correlation (HYSCORE) spectra revealed cross peaks arising from the protons of coordinated water in a clean spectral window from g = 3.0 to 2.3. These cross peaks were absent for the {FeNO}(7)(N2O3) complex. HYSCORE spectra were analyzed using a straightforward model for defining the spin Hamiltonian parameters of bound water and showed that, for the {FeNO}(7)(N2O2)(H2O) complex, a single water conformer with an isotropic hyperfine coupling, Aiso = 0.0 ± 0.3 MHz, and a dipolar coupling of T = 4.8 ± 0.2 MHz could account for the data. For the {FeNO}(7)(N2O)(H2O)2 complex, the HYSCORE cross peaks assigned to coordinated water showed more frequency dispersion and were analyzed with discrete orientations and hyperfine couplings for the two water molecules that accounted for the observed orientation-selective contour shapes. The use of three-pulse electron spin echo envelope modulation (ESEEM) data to quantify the number of water ligands coordinated to the {FeNO}(7) centers was explored. For this aspect of the study, HYSCORE spectra were important for defining a spectral window where empirical integration of ESEEM spectra would be the most accurate.

Solution and solid state studies on the interactions of protonated cytosine salts. I. Influence of anions on 1H nmr spectra and degree of protonation in mixtures of protonated and unprotonated cytosine and derivatives

Abstract Protonated salts of cytosine, cytidine, and 1-methylcytosine have been prepared and studied in dimethylsulfoxide using 1H nmr spectroscopy. Evidence is presented that moderately strong interactions occur between the protonated base and the counterions for chloride salts whereas no interaction was detected for nitrate or perchlorate salts. The 1H nmr spectra of mixtures of 1-methylcytosine and cytidine with some of the corresponding protonated salts did not reveal base pairing. However, such mixtures for cytosine had 1H nmr spectra in which some resonances were displaced to lower field than predicted by the composition of the mixtures. Calculations suggest that the especially large downfield shifts observed for the “amino” NH resonances in such mixtures result from chemical exchange of the amino group, with the N(I)H and N(3)H groups, which are normally found at much lower field. In the absence of added unprotonated species, the 1H nmr spectra revealed that the protons of the −NH2 group of the cytosine derivatives were magneticallv inequivalent, regardless of counteranion. In the presence of the corresponding unprotonated species, these resonances are broadened and difficult to detect. This observation sheds new light on the reason for some errors in pioneering studies aimed at establishing the predominant cytosine tautomer with 1H nmr.