Proton transfers in hydrogen bonded systems. Electron correlation effects in (H3NHOH2)+

The energetics of proton transfer between the N and O atoms of (H₃NHOH₂)⁺ are calculated via ab initio molecular orbital methods. A single-well potential is obtained at the equilibrium intermolecular separation Inclusion of electron correlation via the POL CI technique produces a less steep potential, reducing the energy barrier to proton transfer at greater NO distances.     

Separation and quantitation of components in FD&C Red No. 3 using capillary electrophoresis

The use of capillary electrophoresis as a technique to separate and quantitate components of FD&C Red No. 3 (erythrosine, color index No. 45430) is described. The fluorescein isomers, 2',4',5'-triiodofluorescein (2,4,5-I3F) and 2',4',7'-triiodofluorescein (2,4,7-I3F), the most abundant by-products formed during the preparation of the dye, were selected for quantitation studies. The separation of other lower halogenated impurities was also demonstrated. Electrophoretic mobility of the compounds was achieved in a 50 mM borate, 25 mM sodium dodecyl sulfate buffer at pH 9.3. The limits of quantitation were found to be 0.15% (w/w) (2,4,5-I3F) and 0.14% (w/w) (2,4,7-I3F) (relative to the mass of FD&C Red No. 3). The method is linear from 0.08 to 20.0% (w/w) for 2,4,5-I3F and between 0.06 and 17.0% (w/w) for 2,4,7-13F. In addition, relative standard deviations of 2.03 and 5.11% were determined from precision studies in the repeat analysis of FD&C Red No. 3 for 2,4,5-I3F and 2,4,7-I3F, respectively. Overall, the CE method produced data in excellent agreement with the reference HPLC method, used considerably less solvent and sample, generated less waste and was found to be considerably more cost efficient.     

Designed Beta‐Turn Mimic Based on the Allylic‐Strain Concept: Evaluation of Structural and Biological Features by Incorporation into a Cyclic RGD Peptide (Cyclo(‐L‐arginylglycyl‐L‐α‐aspartyl‐))

The (3R,5S,6E,8S,10R)‐11‐amino‐3,5,8,10‐tetramethylundec‐6‐enoic acid (ATUA; 1 ), which was designed as a βII′‐turn mimic according to the concepts of allylic strain and 2,4‐dimethylpentane units, was incorporated into a cyclic RGD peptide. The three‐dimensional structure of cyclo(‐RGD‐ATUA‐) (=cyclo(‐Arg‐Gly‐Asp‐ATUA‐)) 4 in H₂O was determined by NMR techniques, distance geometry calculations and molecular‐dynamics simulations. The RGD sequence of 4 shows high conformational flexibility but some preference for an extended conformation. The structural features of the RGD sequence of 4 were compared with the RGD moiety of cyclo(‐RGDfV‐) (=cyclo(‐Arg‐Gly‐Asp‐D ‐Phe‐Val‐)). In contrast to cyclo(‐RGDfV‐), which is a highly active αvβ3 antagonist and selective against αIIbβ3, cyclo(‐RGD‐ATUA‐) shows a lower activity and selectivity. The structure of the ATUA residue in the cyclic peptide resembles a βII′‐turn‐like conformation. Its middle part, adjacent to the C?C bond, strongly prefers the designed and desired structure.     

Die Umlagerung substituierter Aminoacrylderivate. Präparative anwendungsbreite

The addition of carboxylic acids to dimethylamino-propinal ( 1a ) and 4-dimethyl-amino-but-3-in-2-on ( 1b ) gives, after rearrangement of the very instable primary adducts ( 2 ), Z-3-acetoxy-N,N-dimethylacrylamides and -crotonamides 3 to 8 in excellent yields and in a stereospecific manner. Similarly, the adducts of HCl and HBr to the alkynes 1a and 1b may be rearranged at low temperature by traces of acid to cis/trans equilibria of 3-halo-acrylamides and -crotonamides 9 and 10 . - On the other hand, treatment of 3-alkoxy-3-dimethylaminoacrolein with traces of acid yields alkylesters of E-3-dimethylaminoacrylic acid ( 12 , X = OR). - The preparative aspects of the rearrangement are discussed, and a brief outline of the spectroscopic properties of the compounds 3 to 8 is given.     

Energetic and stereochemical effects of the protein environment on substrate: a theoretical study of methylmalonyl-CoA mutase

QM/MM methods were used to study the isomerization step from (2R)-methylmalonyl-CoA to succinyl-CoA. A pathway via a "fragmentation-recombination" mechanism is ruled out on energetic grounds. For the other radicalic pathway, involving an addition recombination step, geometries and vibrational contributions have been determined, and a barrier height of 11.70 kcal/mol was found. The effect of adjacent hydrogen-donating groups was found to reduce the energy barrier by 1-2 kcal/mol each and thus to provide a significant catalytic effect for this reaction. By means of molecular dynamics studies, the stereochemistry of the methylmalonyl-CoA mutase catalyzed reaction was examined. It is shown that TYR89 is essential for maintaining stereoselectivity of the abstraction of a hydrogen in the backreaction. The subsequent selective formation of one isomer of methylmalonyl-CoA is probably due to the presence of a bulky side chain.     

Double proton transfer in the isolated and DNA-embedded guanine-cytosine base pair

The energetics and dynamics of double proton transfer (DPT) is investigated theoretically for the Watson-Crick conformation of the guanine-cytosine (GC) base pair. Using semiempirical density functional theory the isolated and DNA-embedded GC pair is considered. Differences in the energetics and dynamics of DPT thus addresses the question of how relevant studies of isolated base pairs are for the understanding of processes occurring in DNA. Two-dimensional potential energy surfaces involving the transferring hydrogen atoms and the proton donors and acceptors are presented for both systems. The DPT reaction is accompanied by a contraction of the distance between the two bases with virtually identical energetic barriers being 18.8 and 18.7 kcal/mol for the isolated and DNA-embedded system, respectively. However, the transition state for DPT in the DNA-embedded GC pair is offset by 0.1 A to larger N-H separation compared to the isolated GC pair. Using activated ab initio molecular dynamics, DPT is readily observed for the isolated base pair with a minimal amount of 21.4 kcal/mol of initial average kinetic energy along the DPT normal mode vector. On a time scale of approximately 100 fs DPT has occurred and the excess energy is redistributed. For the DNA-embedded GC pair considerably more kinetic energy is required (30.0 kcal/mol) for DPT and the process is completed within one hydrogen vibration. The relevance of studies of isolated base pairs and base pair analogs in regard of reactions or properties involving DNA is discussed.     

Chemistry of constrained dioxocyclam ligands with Co(III): unusual examples of C-H and C-N bond cleavage

The reactions between H(2)dc3 and Co(acac)(3) have been studied in the presence and absence of base. In the presence of base, a complex with an intramolecular Co-C bond, Co(dc3-C-(8))(H(2)O), 1, is formed, presumably through heterolytic C-H bond activation. An X-ray crystallographic study demonstrates the presence of a Co-C bond and shows that the diazacyclooctane (daco) subunit adopts the chair-boat conformation with respect to the metal. The cobalt-carbon bond induces strain in the macrocycle as demonstrated by bond angles significantly deviating from tetrahedral. The (13)C NMR resonance of the carbon atom bound to cobalt (-10.5 ppm) suggests significant ionic character in the cobalt-carbon bond. However, we were unable to cleave this bond in the presence of strong acid. In the absence of base, the reaction of Co(acac)(3) with H(2)dc3 resulted in C-N cleavage of the ligand and the formation of a complex of dioxocyclam, Co(dc)(acac), 2. This complex has subsequently been prepared in high yield by the reaction of Co(acac)(3) with dioxocyclam. An X-ray crystallographic study demonstrates that dioxocyclam adopts the heretofore unreported cis configuration, having folded along a N-Co-N axis that is perpendicular to the Co-acac plane.     

Conformational analysis of self-organized monolayers with scanning tunneling microscopy at near-atomic resolution

We describe the synthesis and a novel approach to the conformational analysis of 2,2'-bipyridines (bpy) bearing aromatic rich Frechet-type dendritic wedges of the first and second generation as substituents. The evaporation of solutions of these new ligands on graphite surfaces under ambient conditions results in the formation of self-organized monolayers. Scanning tunneling microscopy (STM) investigations of the monolayers under ambient conditions (air, 298 K) gave images at submolecular and near-atomic resolution. The analysis of the STM images includes the following processes: (i) identification and reproduction of potential homoconformational domains, (ii) exclusion of improper data using quality criteria for drift and feedback artifacts, (iii) compilation of running averages and checking for averaging artifacts, (iv) analysis of three-dimensional and contour plots, (v) calculation of the HOMO properties of the free molecules, and (vi) final conformational assignment based on all accessible information. Following this procedure, two different conformations could be assigned to domains observed in the monolayers of the first-generation (G1) and second-generation (G2) dendritic compounds. Homoconformational domains are observed side-by-side. The different conformations arise from syn or anti arrangements at the ether substituents. An additional conformational effect is found upon treating the G1 domains with HCl gas, when a partial rearrangement of the bpy from trans to cis occurs, concomitant with protonation.     

Structure and properties of the dendron-encapsulated polyoxometalate (C(52)H(60)NO(12))(12)[(Mn(H(2)O))(3)(SbW(9)O(33))(2)], a first generation dendrizyme

Combining analytical and theoretical methods, we present a detailed study of a heteropolytungstate cluster encapsulated in a shell of dendritically branching surfactants, namely (C(52)H(60)NO(12))(12)[(Mn(H(2)O))(3)(SbW(9)O(33))(2)], 3. This novel surfactant-encapsulated cluster (SEC) self-assembles spontaneously from polyoxometalate-containing solutions treated with a stoichiometric amount of dendrons. Compound 3 exhibits a discrete supramolecular architecture in which a single polyoxometalate anion resides in a compact shell of dendrons. Our approach attempts to combine the catalytic activity of polyoxometalates with the steric properties of tailored dendritic surfactants into size-selective catalytic systems. The structural characterization of the SEC is based on analytical ultracentrifugation (AUC) and small-angle neutron scattering (SANS). The packing arrangement of dendrons at the cluster surface is gleaned from molecular dynamics (MD) simulations, which suggests a highly porous shell structure due to the dynamic formation of internal clefts and cavities. From analysis of the MD trajectory of 3, a theoretical neutron-scattering function is derived that is in good agreement with experimental SANS data. Force field parameters used in MD simulations are partially derived from a quantum mechanical geometry optimization of [(Zn(H(2)O))(3)(SbW(9)O(33))(2)](12)(-), 2b, at the density functional theory (DFT) level. DFT calculations are corroborated by X-ray structure analysis of Na(6)K(6)[(Zn(H(2)O))(3)(SbW(9)O(33))(2)].23H(2)O, which is isostructural with the catalytically active Mn derivative 2a. The combined use of theoretical and analytical methods aims at rapidly prototyping smart catalysts ("dendrizymes"), which are structurally related to naturally occurring metalloproteins.