Theoretical Study of the Catalytic Mechanism of the Cu-Only Superoxide Dismutase.

The catalytic mechanisms for the wild-type and the mutated Cu-only superoxide dismutase were studied using the hybrid density functional B3LYP and a quantum chemical cluster approach. Optimal protonation states of the active site were examined for each stage of the catalytic cycle. For both the reductive and the oxidative half-reactions, the arrival of the substrate O2•- was found to be accompanied by a charge-compensating H+ with exergonicities of -15.4 kcal·mol and -4.7 kcal·mol, respectively. The second-sphere Glu-110 and first-sphere His-93 were suggested to be the transient protonation site for the reductive and the oxidative half-reactions, respectively, which collaborates with the hydrogen bonding water chain to position the substrate near the redox-active copper center. For the reductive half-reaction, the rate-limiting step was found to be the inner-sphere electron transfer from the partially coordinated O2•- to CuII with a barrier of 8.1 kcal·mol. The formed O2 is released from the active site with an exergonicity of -14.9 kcal·mol. For the oxidative half-reaction, the inner-sphere electron transfer from CuI to the partially coordinated O2•- was found to be accompanied by the proton transfer from the protonated His-93 and barrierless. The rate-limiting step was found to be the second proton transfer from the protonated Glu-110 to HO2- with a barrier of 7.3 kcal·mol. The barriers are reasonably consistent with experimental activities, and a proton-transfer rate-limiting step in the oxidative half-reaction could explain the experimentally observed pH-dependence. For the E110Q CuSOD, Asp-113 was suggested to be likely to serve as the transient protonation site in the reductive half-reaction. The rate-limiting barriers were found to be 8.0 and 8.6 kcal·mol, respectively, which could explain the slightly lower performance of E110X mutants. The results were found to be stable, with respect to the percentage of exact exchange in B3LYP.

Theoretical study of the mechanism of the manganese catalase KatB.

The mechanism of the H2O2 disproportionation catalyzed by the manganese catalase (MnCat) KatB was studied using the hybrid density functional theory B3LYP and the quantum chemical cluster approach. Compared to the previous mechanistic study at the molecular level for the Thermus thermophilus MnCat (TTC), more modern methodology was used and larger models of increasing sizes were employed with the help of the high-resolution X-ray structure. In the reaction pathway suggested for KatB using the Large chemical model, the O-O homolysis of the first substrate H2O2 occurs through a µ-η1:η1 coordination mode and requires a barrier of 10.9 kcal/mol. In the intermediate state of the bond cleavage, two hydroxides form as terminal ligands of the dimanganese cluster at the Mn2(III,III) oxidation state. One of the two Mn(III)-OH- moieties and a second-sphere tyrosine stabilize the second substrate H2O2 in the second-sphere of the active site via hydrogen bonding interactions. The H2O2, unbound to the metals, is first oxidized into HO2· through a proton-coupled electron transfer (PCET) step with a barrier of 9.5 kcal/mol. After the system switches to the triplet surface, the uncoordinated HO2· replaces the product water terminally bound to the Mn(II) and is then oxidized into O2 spontaneously. Transition states with structural similarities to those obtained for TTC, where µ-η2-OH-/O2- groups play important roles, were found to be higher in energy.

Geometric structures of Ge(n) (n=34-39) clusters.

The structures of Ge(n) (n=34-39) clusters were searched by a genetic algorithm using a tight-binding interatomic potential. First-principles calculations based on density functional theory were performed to further identify the lowest-energy structures. The calculated results show that Ge(n) (n=34-39) clusters favor prolate or Y-shaped three-arm structures consisting of two or three small stable clusters (Ge(6), Ge(7), Ge(9), or Ge(10)) linked by a Ge(6) or Ge(9) bulk unit. The calculated results suggest the transition point from prolate to Y-shaped three-arm structures appears at Ge(35) or Ge(36).

Platelike structures of semiconductor clusters Ge(n) (n = 40-44).

The structures of Ge(n) (n=40-44) clusters were searched by genetic algorithm combined with a tight-binding method. First-principles calculations based on density functional theory were performed to further optimize the isomer structures. The calculated results show that Ge(n) (n=40-44) clusters favor platelike structures, consisted of four small magic clusters (Ge(9) or Ge(10)), and a Ge(4) core. The Ge(4) core along with the parts of the four linked small clusters forms a diamond segment. The cluster mobilities of the most stable structures are in good agreement with the experimental data.

Structures and stabilities of Pb(n) (n

We have performed global structural optimizations for neutral lead clusters Pb(n) (n = 2-20) by using a genetic algorithm (GA) coupled with a tight-binding (TB) potential. The low-energy structures identified from a GA/TB search were further optimized at the DFT-PBE level. The calculated results show that the Pb(n) (14 < n

Theoretical study on stabilities of multiple hydrogen bonded dimers.

A series of self-constituted multiple hydrogen bonded (MHB) complexes has been investigated systematically by density functional theory (PBE1PBE /6-31G**), the Morokuma energy decomposition method (HF/6-31G**) and MP2 (6-31G** and 6-311++G**) calculation. We have discovered that (i) for doubly hydrogen bonded (DHB) complexes, both the interaction energy and stability increase with the charge transfer energy; (ii) for quadruple hydrogen bonded (QHB) complexes, cooperativity is the most important factor determining stability of the complex: stronger cooperative energy correlates well with larger interaction energy and thus more stable complex and vice versa; (iii) correlation energy plays an important role in intermolecular interactions. The correlation energy, mainly consisting of dispersive energy, also exhibits cooperativity in MHB dimers: positive for M-aadd and generally negative for other complexes.

Bending effect on the stabilities of quadruple hydrogen bonding systems: theoretical study of a series of self-constituted quadruple hydrogen bonded complexes (C9H9N5O2)2.

A series of self-constituted quadruple hydrogen bonded (QHB) complexes (C9H9N5O2)2 has been designed and studied systematically using density functional theory (B3LYP/6-31G**) and the Morokuma energy decompose method (HF/6-31G**). Despite very similar structures of these systems, the interaction energies fluctuate significantly from 22.33 to 88.30 kcal mol(-1). To explain this somewhat unexpected observation, several doubly hydrogen bonded (DHB) systems were designed and a "bending effect" hypothesis was presented. According to the hypothesis, the spatial arrangement of hydrogen bonds is less important than their intensity arrangement.

Solvophobically-driven oligo(ethylene glycol) helical foldamers. Synthesis, characterization, and complexation with ethane-1,2-diaminium.

Oligo(ethylene glycols) 1a-h, which are incorporated with one to eight 2,3-naphthylene units, respectively, have been synthesized and characterized. The conformational changes of the new oligomers have been investigated in chloroform-acetonitrile binary solvents by the UV-vis, (1)H NMR, and fluorescent spectroscopy. It has been revealed that the naphthalene units in hexamer 1f, heptamer 1g, and octamer 1h are driven by solvophobic interaction to stack in polar solvents. As a result, compact helical conformations are formed that give rise to a cavity similar to that of 18-crown-6. Shorter oligomers 1b-e exhibit weaker folding tendency. (1)H NMR studies reveal that 1f-h are able to complex ammonium or ethane-1,2-diaminium 19, but not secondary ammonium compounds. The association constants of complexes 1f.19, 1g.19, and 1h.19 in acetonitrile are determined to be 3.5(+/-0.4) x 10(3), 1.0(+/-0.12) x 10(4), and 2.5(+/-0.4) x 10(4) M(-1), respectively, with the (1)H NMR titration method. For comparison, hexamer 22, which incorporates six 1,5-naphthylene units, is also prepared. The UV-vis and fluorescent investigations show that 22 is also able to fold in polar solvents, but no helical structure can be produced due to mismatch of the stacking naphthalene units and consequently there is no obvious complexation between 22 with ethane-1,2-diaminium ion. The structures of the longest foldamer 1h and its complex with 19 have been studied with molecular mechanics calculations. This work represents a new approach to building folding conformations from flexible linear molecules.

Hydrogen bonded oligohydrazide foldamers and their recognition for saccharides.

This paper describes the synthesis and characterization of the first series of hydrogen bonding-driven hydrazide foldamers and their recognition for alkyl saccharides in chloroform. Oligomers 1, 2-4, 5, 6, and 7, which contain one, two, four, six, or twelve repeated dibenzoyl hydrazide residues, respectively, have been prepared. The rigid and planar conformations of 1 and 2 or 4 have been established with X-ray analysis and (1)H NMR spectroscopy, whereas the folding and helical conformations of 5-7 have been evidenced by the 1D and 2D (1)H NMR and IR spectroscopy and molecular mechanics calculations. Molecular mechanics calculations also revealed that 5, 6, and 7 possess a rigid cavity with size of ca. 10.6 to 11.1 A, and half of the carbonyl groups in the folding conformations are orientated inwardly inside the cavity. (1)H NMR and CD experiments revealed that 5-7 efficiently complex alkylated mono- and disaccharides 32-35 in chloroform. The association constants (K(assoc)) of the complexes have been determined with the (1)H NMR and fluorescent titration methods. The energy-minimized conformation of 6.34 has been obtained with molecular mechanics calculation. The hydrazide-based folding structures described here represent novel examples of hydrogen bonding-driven foldamers that act as artificial receptors for selective molecular recognition.

Zipper-featured delta-peptide foldamers driven by donor--acceptor interaction. Design, synthesis, and characterization.

Donor-acceptor interaction between electron-rich 1,5-dioxynaphthalene (DAN) and electron-deficient pyromellitic diimide (PDI) has been utilized to induce the formation of a new kind of zipper-featured delta-peptide foldamers. Seven l-ornithine-based delta-peptides 1a-g, in which one to three DNA and PDI units are incorporated to the two ends of the peptide backbones, respectively, have been designed and prepared by the standard liquid-phase synthetic method. (1)H NMR, UV-vis, and fluorescent quenching studies reveal that all the delta-peptides adopt folding conformations in nonpolar chloroform and polar DMF as a result of intramolecular donor-acceptor interaction between the DAN and PDI units. The folding states become more compact for the peptide skeletons possessing more donor-acceptor interacting sites. Variable-temperature UV-vis experiments indicate that, although the folding is a dynamic process, the folding state can remain even at 150 degrees C in DMF. Circular dichroism (CD) investigations reveal that the new generation of delta-peptides have similar folding patterns. A zipper-featured folding motif has been proposed for the new generation of delta-peptide foldamers. Molecular modeling has generated two most stable folding states for the longest delta-peptide 1g, with an energy difference of 26.80 kcal/mol.

Hydrazide-based quadruply hydrogen-bonded heterodimers. Structure, assembling selectivity, and supramolecular substitution.

This paper describes the synthesis, self-assembly, and characterization of a new class of highly stable hydrazide-based quadruply hydrogen-bonded heterodimers. All of the hydrazide-derived heterodimers possess the complementary ADDA-DAAD hydrogen-bonding sequences. Hydrazide derivatives 1, which has two intramolecular S(6) RO.H-N hydrogen bonds, and 2 complex to afford two fastly exchanging isomeric heterodimers 1.2 and 1.2' in chloroform, as a result of two different conformational arrangements of 2. An average binding constant K(assoc) of 4.7 x 10(4) M(-)(1) was determined for heterodimer 1.2 and 1.2' by (1)H NMR titration of 1 with changing 2 in chloroform-d. In contrast, 1 binds 11 and 12, both of which are introduced with two intramolecular S(6) hydrogen bonds, to exclusively afford heterodimers 1.11 and 1.12, with K(assoc) values of 1.8 x 10(4) and 5.0 x 10(2) M(-)(1), respectively. Fluorine-containing 19, which has a hydrazide skeleton identical to that of 1 but two intramolecular S(6) F.H-N hydrogen bonds, can also complex with 2, 11, and 12, to afford heterodimers 19.2, 19.2', 19.11, and 19.12, with K(assoc) values of of 1.2 x 10(4) (average value for 19.2 and 19.2'), 5.4 x 10(3), and 1.9 x 10(2) M(-)(1), respectively. The structures of the new heterodimers have been proven with NOESY, IR, and VPO (for some of the heterodimers) experiments. Moreover, 1 and 19 can also strongly bind 2,7-dilauroylamido-1,8-naphthyridine 23 to afford dimers 1.23 and 19.23 with K(assoc) values of 6.0 x 10(5) and 1.4 x 10(5) M(-)(1), respectively. Adding 1 to the 1:1 solution of 23 and 1-octyl-3-(4-oxo-3,4-dihydro-pyrido[2,3-d]pyrimidin-2-yl)urea 24 or 1-octyl-3-(4-oxo-1,4-dihydro-pyrimidin-2-yl)urea 25, which had been developed initially by Zimmerman and Meijer, respectively, induces dimers 23.24 and 23.25 to dissociate, leading to the formation of dimers 1.23 and 24.24 or 25.25, respectively. The new hydrazide-based hydrogen-bonding modules described are useful building blocks for self-assembly and open a new avenue to recognition between discrete supramolecular species.

First zipper-featured molecular duplexes driven by cooperative donor-acceptor interaction.

[structure: see text] The first class of zipper-shaped artificial duplexes, which are driven by multiple donor-acceptor interactions between electron-rich 1,5-dioxynaphthalene or 1,4-dioxybenzene and electron-deficient pyromellitic dimide units, have been studied in organic media by (1)H NMR, UV-vis, and vapor pressure osmometry. (1)H NMR binding investigations reveal substantial cooperativity of the donor-acceptor interaction in the duplexes.