Cages versus Sheets: A Critical Comparison in the Size Range Expected for Methylaluminoxane (MAO)

New cage models (MeAlO)_n(Me₃Al)_m (n=16, m=6 or 7) isomeric with previously reported sheet models for the principle activator found in hydrolytic MAO (h-MAO) are compared at M06-2X and MN15 levels of theory using density functional theory with respect to their thermodynamic stability. Reactivity of the neutrals or corresponding anions with formula [(MeAlO)₁₆(Me₃Al)₆Me]⁻ towards chlorination, and loss of Me₃Al is explored while reactivity of the neutrals towards formation of contact- and outer-sphere ion pairs from Cp₂ZrMe₂ and Cp₂ZrMeCl is examined. The results suggest on balance that a cage model for this activator is less consistent with experiment than an isomeric sheet model, although the latter are more stable based on free energy.     

An $$L^1$$-Estimate for Certain Spectral Multipliers Associated with the Ornstein–Uhlenbeck Operator

We study a class of spectral multipliers \(\phi (L)\) for the Ornstein–Uhlenbeck operator L arising from the Gaussian measure on \(\mathbb {R}^n\) and find a sufficient condition for integrability of \(\phi (L)f\) in terms of the admissible conical square function and a maximal function.     

Generating conformer ensembles using a multiobjective genetic algorithm

The task of generating a nonredundant set of low-energy conformations for small molecules is of fundamental importance for many molecular modeling and drug-design methodologies. Several approaches to conformer generation have been published. Exhaustive searches suffer from the exponential growth of the search space with increasing degrees of conformational freedom (number of rotatable bonds). Stochastic algorithms do not suffer as much from the exponential increase of search space and provide a good coverage of the energy minima. Here, the use of a multiobjective genetic algorithm in the generation of conformer ensembles is investigated. Distance geometry is used to generate an initial conformer, which is then subject to geometric modifications encoded by the individuals of the genetic algorithm. The geometric modifications apply to torsion angles about rotatable bonds, stereochemistry of double bonds and tetrahedral chiral centers, and ring conformations. The geometric diversity of the evolving conformer ensemble is preserved by a fitness-sharing mechanism based on the root-mean-square distance of the atomic coordinates. Molecular symmetry is taken into account in the distance calculation. The geometric modifications introduce strain into the structures. The strain is relaxed using an MMFF94-like force field in a postprocessing step that also removes conformational duplicates and structures whose strain energy remains above a predefined window from the minimum energy value found in the set. The implementation, called Balloon, is available free of charge on the Internet ( http://www.abo.fi/~mivainio/balloon/).     

Structural properties of ionic detergent aggregates: a large-scale molecular dynamics study of sodium dodecyl sulfate

The properties of sodium dodecyl sulfate (SDS) aggregates were studied through extensive molecular dynamics simulations with explicit solvent. First, we provide a parametrization of the model within Gromacs. Then, we probe the kinetics of aggregation by starting from a random solution of SDS molecules and letting the system explore its kinetic pathway during the aggregation of multiple units. We observe a structural transition for the surfactant aggregates brought upon by a change in temperature. Specifically, at low temperatures, the surfactants form crystalline aggregates, whereas at elevated temperatures, they form micelles. We also investigate the dependence of aggregation kinetics on surfactant concentration and report on the molecular level structural changes involved in the transition.     

Thio effects on the departure of the 3'-linked ribonucleoside from diribonucleoside 3',3'-phosphorodithioate diesters and triribonucleoside 3',3',5'-phosphoromonothioate triesters: implications for ribozyme catalysis

To provide a solid chemical basis for the mechanistic interpretations of the thio effects observed for large ribozymes, the cleavage of triribonucleoside 3',3',5'-phosphoromonothioate triesters and diribonucleoside 3',3'-phosphorodithioate diesters has been studied. To elucidate the role of the neighboring hydroxy group of the departing 3'-linked nucleoside, hydrolysis of 2',3'-O-methyleneadenosin-5'-yl bis[5'-O-methyluridin-3'-yl] phosphoromonothioate (1 a) has been compared to the hydrolysis of 2',3'-O-methyleneadenosin-5'-yl 5'-O-methyluridin-3'-yl 2',5'-di-O-methyluridin-3'-yl phosphoromonothioate (1 b) and the hydrolysis of bis[uridin-3'-yl] phosphorodithioate (2 a) to the hydrolysis of uridin-3'-yl 2',5'-di-O-methyluridin-3'-yl phosphorodithioate (2 b). The reactions have been followed by RP HPLC over a wide pH range. The phosphoromonothioate triesters 1 a,b undergo two competing reactions: the starting material is cleaved to a mixture of 3',3'- and 3',5'-diesters, and isomerized to 2',3',5'- and 2',2',5'-triesters. With phosphorodithioate diesters 2 a,b, hydroxide-ion-catalyzed cleavage of the P--O3' bond is the only reaction detected at pH >6, but under more acidic conditions desulfurization starts to compete with the cleavage. The 3',3'-diesters do not undergo isomerization. The hydroxide-ion-catalyzed cleavage reaction with both 1 a and 2 a is 27 times as fast as that compared with their 2'-O-methylated counterparts 1 b and 2 b. The hydroxide-ion-catalyzed isomerization of the 3',3',5'-triester to 2',3',5'- and 2',2',5'-triesters with 1 a is 11 times as fast as that compared with 1 b. These accelerations have been accounted for by stabilization of the anionic phosphorane intermediate by hydrogen bonding with the 2'-hydroxy function. Thio substitution of the nonbridging oxygens has an almost negligible influence on the cleavage of 3',3'-diesters 2 a,b, but the hydrolysis of phosphoromonothioate triesters 1 a,b exhibits a sizable thio effect, k(PO)/k(PS)=19. The effects of metal ions on the rate of the cleavage of diesters and triesters have been studied and discussed in terms of the suggested hydrogen-bond stabilization of the thiophosphorane intermediates derived from 1 a and 2 a.     

Characterization of the diradical *NSNSC-CNSSN* and [NSNSC-CNSSN][MF6]n (n=1, 2). The first observation of an excited triplet state in dimers of 7pi -CNSSN* radicals

Preparation and full characterization of the main-group diradical *NSNSC-CNSSN*, 8, the MF6- salt (As, Sb) of radical cation +NSNSC-CNSSN*, 8*+, and the AsF6- salt of the dication +NSNSC-CNSSN+, 82+, are presented. 8, a=6.717 (4), b=11.701(2), c=8.269(3) A, alpha=gamma=90, beta=106.69(3) degrees, monoclinic, space group P21/n, Z=4, T=203 K; 8SbF6, a=6.523(2), b=7.780(2), c=12.012(4) A, alpha=91.994(4), beta=96.716(4), gamma=09.177(4) degrees, triclinic, space group P, Z=2, T=198 K; 8[AsF6]2, a=12.7919(14), b=9.5760(11), c=18.532(2) A, alpha=gamma=90, beta=104.034(2) degrees, monoclinic, space group Pn, Z=6, T=198 K. Preparation of 8MF6 was carried out via a reduction of [CNSNS]2[MF6]2 (M=As, Sb) with either ferrocene or a SbPh3-NBu4Cl mixture. In the solid state, diamagnetic 8SbF6 contains centrosymmetric dimers [8*+]2 linked via two-electron four-centered pi*-pi* interactions with a thermally excited triplet state as detected by electron paramagnetic resonance (EPR). This is the first observation of a triplet excited state for a 7pi 1,2,3,5-dithiadiazolyl radical dimer. The singlet-triplet gap of the [-CNSSN*]2 radical pair was -1800+/-100 cm(-1) (-22+/-1 kJ/mol) with the ZFS components |D|=0.0267(6) cm(-1) and |E|=0.0012(1) cm(-1), corresponding to an in situ dimerization energy of ca. -11 kJ/mol. Cyclic voltammetry measurements of 8[AsF6]2 showed two reversible waves associated with a stepwise reduction of the two isomeric rings [E1/2 (+2/+1)=1.03 V; E1/2 (+1/0)=0.47 V, respectively]. 8MF6 (M=As, Sb) was further reduced to afford the mixed main-group diradical 8, containing two isomeric radical rings. In solution, 8 is thermodynamically unstable with respect to *NSSNC-CNSSN*, but is isolable in the solid state because of its low solubility in SO2. Likewise, 8SbF6, 8 is dimeric, with pi*-pi* interactions between different isomeric rings, and consequently diamagnetic; however, a slight increase in paramagnetism was observed upon grinding [from C=6.5(3)x10(-4) emu.K/mol and temperature-independent paramagnetism (TIP)=1.3(1)x10(-4) emu/mol to C=3.2(1)x10(-3) emu.K/mol and TIP=9.0(1)x10(-4) emu/mol], accompanied by an increase in the lattice-defect S=1/2 sites [from 0.087(1) to 0.43(1)%]. Computational analysis using the multiconfigurational approach [CASSCF(6,6)/6-31G*] indicated that the two-electron multicentered pi*-pi* bonds in [8*+]2 and [8]2 have substantial diradical characters, implying that their ground states are diradicaloid in nature. Our results suggest that the electronic structure of organic-radical ion pairs, for example, [TTF*+]2, [TCNE*-]2, [TCNQ*-]2, [DDQ*-]2, and related pi dimers, can be described in a similar way.     

Conformational analysis of lipid molecules by self-organizing maps

The authors have studied the use of the self-organizing map (SOM) in the analysis of lipid conformations produced by atomic-scale molecular dynamics simulations. First, focusing on the methodological aspects, they have systematically studied how the SOM can be employed in the analysis of lipid conformations in a controlled and reliable fashion. For this purpose, they have used a previously reported 50 ns atomistic molecular dynamics simulation of a 1-palmitoyl-2-linoeayl-sn-glycero-3-phosphatidylcholine (PLPC) lipid bilayer and analyzed separately the conformations of the headgroup and the glycerol regions, as well as the diunsaturated fatty acid chain. They have elucidated the effect of training parameters on the quality of the results, as well as the effect of the size of the SOM. It turns out that the main conformational states of each region in the molecule are easily distinguished together with a variety of other typical structural features. As a second topic, the authors applied the SOM to the PLPC data to demonstrate how it can be used in the analysis that goes beyond the standard methods commonly used to study the structure and dynamics of lipid membranes. Overall, the results suggest that the SOM method provides a relatively simple and robust tool for quickly gaining a qualitative understanding of the most important features of the conformations of the system, without a priori knowledge. It seems plausible that the insight given by the SOM could be applied to a variety of biomolecular systems and the design of coarse-grained models for these systems.     

Impact of reductive cleavage of an intramolecular disulfide bond containing cationic gemini surfactant in monolayers and bilayers

The properties of a novel disulfide-bond-containing gemini surfactant bis[N,N-dimethyl-N-hexadecyl-N-(2-mercaptoethyl)ammonium bromide] disulfide (DSP) were studied using a Langmuir balance, supported monolayers, differential scanning calorimetry, giant vesicles, and LUVs. In 150 mM NaCl the cmc for DSP was 7.5 microM whereas that of the monomer N,N-dimethyl-N-hexadecyl-N-(2-mercaptoethyl)ammonium bromide (MSP) was 12.1 microM. Both surfactants exhibited single endotherms upon DSC, with peak temperatures Tm at 21.7 and 20.1 degrees C for DSP and MSP, respectively. The endotherm for MSP was significantly broader indicating less cooperative melting. Both in monolayers and in vesicles reductive cleavage of the disulfide bond of DSP could be obtained by glutathione (GSH). For Langmuir films of DSP the addition of GSH into the subphase led to a decrease in surface pressure pi as well as surface dipole potential psi. Although the cleavage by GSH was significantly slower in the presence of a charge saturating concentration of DNA, it did not prevent the reaction. The resulting monomers detached from supported monolayers, leading to loss of affinity of the surface for DNA. Disruption of giant vesicles containing DSP within approximately 30 s following a local injection of GSH was observed, revealing membrane destabilization.