A simple approach for improving the hybrid MMVB force field: application to the photoisomerization of s-cis butadiene

MMVB is a QM/MM hybrid method, consisting of a molecular mechanics force field coupled to a valence bond Heisenberg Hamiltonian parametrized from ab initio CASSCF calculations on several prototype molecules. The Heisenberg Hamiltonian matrix elements Q(ij) and K(ij), whose expressions are partitioned here into a primary contribution and second-order correction terms, are calculated analytically in MMVB. When the original MMVB force field fails to produce potential energy surfaces accurate enough for dynamics calculations, we show that significant improvements can be made by refitting the second-order correction terms for the particular molecule(s) being studied. This "local" reparametrization is based on values of K(ij) extracted (using effective Hamiltonian techniques) from CASSCF calculations on the same molecule(s). The method is demonstrated for the photoisomerization of s-cis butadiene, and we explain how the correction terms that enabled a successful MMVB dynamics study [Garavelli, M.; Bernardi, F.; Olivucci, M.; Bearpark, M. J.; Klein, S.; Robb, M. A. J Phys Chem A 2001, 105, 11496] were refitted.     

The deprotonation of benzyl alcohol radical cations: a mechanistic dichotomy in the gas phase as in solution

The gas-phase acidity of ionized benzyl alcohol and of some of its derivatives with selected reference bases has been studied by Fourier Transform Ion Cyclotron Resonance (FT-ICR) mass spectrometry. The aim was to relate the gas-phase reactivity to the behavior in aqueous solution of the radical cations of benzyl alcohols bearing methoxy substituent(s) on the phenyl ring which are known to undergo deprotonation at both the CH2 and OH groups. The dual reactivity behavior is confirmed in the gas phase, in which the prototypical ion, C6H5CH2OH*+, is deprotonated at both the CH2 and OH groups, whereas the ring hydrogens are not involved. An increasing extent of O-deprotonation is shown as the strength of the base increases. Appropriate methyl substitution, as in the radical cations of C6H5C(Me)2OH and C6H5CH2OMe, allows only O- or C-acidity. The two processes are characterized by comparable thermodynamic features with a Gas-phase Basicity (GB) value of 852 kJ mol(-1) for the cumyloxyl radical and 850 kJ mol(-1) for the alpha-methoxybenzyl radical. The possible origin of the observed mechanistic dichotomy is discussed.     

Ab initio molecular modeling of 13C NMR chemical shifts of polymers. 1. Ethylene–norbornene copolymers

Cycloolefin copolymers (COC) have recently raised much interest because of their excellent thermal and optical properties, largely determined by the chain composition and stereochemistry. Previous force‐field computations allowed us to define the main conformational characteristics of ethylene–norbornene (E–N) copolymers and to contribute to the elucidation of their microstructure on the basis of empirical relationships between conformation and ¹³C nuclear magnetic resonance (NMR) chemical shifts. A thorough test of ab initio ¹³C chemical shifts computations [gauge‐invariant atomic orbitals (GIAO)] on known cases shows that the agreement with experimental data is quite good, especially with the MPW1PW91 density functional theory (DFT), using the 6‐311+G(2d,p) basis set on properly energy‐minimized structures. We applied this method on proper model compounds to confirm the signal assignment of the spectra of E–N copolymers in the presence of norbornene microblocks, where strong effects arising from ring distortions are expected to occur. The results nicely confirm the latest assignment of norbornene signals belonging to ENNE sequences. This shows the great potentialities of GIAO/DFT computations with regard to complex spectra interpretation and polymer microstructural investigations. © 2002 Wiley Periodicals, Inc. Int J Quantum Chem, 2002     

Reaction of [CpRu(CH3CN)3]PF6 with bidentate ligands: structural characterization of [{CpRu(CH3CN)2}2(μ-η-dppe)](PF6)2 [dppe=1,2-bis(diphenylphosphino)ethane]

The reaction of [CpRu(CH₃CN)₃]PF₆ with the bidentate ligands L-L=1,2-bis(diphenylphosphino)ethane, dppe, and (1-diphenylarsino-2-diphenylphosphino)ethane, dpadppe, affords mononuclear or dinuclear complexes of formula [CpRu(η²-L-L)(CH₃CN)]PF₆, [{CpRu(CH₃CN)₂}₂(μ-η^1:1-L-L)](PF₆)₂ and [{CpRu(CH₃CN)}₂(μ-η^1:1-L-L)₂](PF₆)₂ (L-L=dppe, dpadppe). All of the compounds are characterized by microanalysis and NMR [¹H and ³¹P{¹H}] spectroscopy. The crystal structure of [{CpRu(CH₃CN)₂}₂(μ-η^1:1-dppe)](PF₆)₂ has been determined by X-ray diffraction analysis. The complex exhibits a dppe ligand bridging two CpRu(CH₃CN)₂ fragments.     

Hydrophobic interaction chromatography coupled with atomic fluorescence spectrometric detection Effect of the denaturation on the determination of thiolic proteins

Hydrophobic interaction chromatography coupled online with chemical vapour atomic fluorescence spectrometry (HIC-CVGAFS) has been optimized for the analysis of thiolic proteins in denaturing conditions. Proteins are pre-column simultaneously denatured and derivatized in phosphate buffer solution containing 8.0 mol dm⁻³ urea and p-hydroxymercurybenzoate (PHMB) and the derivatized denatured proteins are separated on a silica HIC Eichrom Propyl column in the presence of 8.0 M urea in the mobile phase. Post-column online reaction of derivatized denatured proteins with bromine, generated in situ by KBr/KBrO₃ in HCl medium, allowed the fast conversion of the uncomplexed PHMB and of the PHMB bound to proteins to inorganic mercury also in presence of urea. Hg²⁺, present in solution as Hg²⁺-urea complex, is selectively detected by AFS in a Ar/H₂ miniaturized flame after sodium borohydride reduction to Hg. Under optimized conditions, online bromine treatment gives a 100±2% recovery of both free and protein-complexed PHMB. Denatured glyceraldehyde-3-phosphate dehydrogenase, aldolase, lactate dehydrogenase, trioso phosphate isomerase and β-lactoglobulin have been examined. As the sensitivity and limit of detection of proteins in the HIC-CVGAFS apparatus depends on number of SH groups reacting with PHMB, the denaturation process, which increases the number of PHMB-reactive thiolic groups in proteins, improves the analytical performances of the described system in protein analysis. The detection limit for the denatured proteins examined was found in the range of 10⁻¹⁰-10⁻¹² mol dm⁻³, depending on the considered protein, with linear calibration curves spanning over four decades of concentration.     

Role of recycling in improving the performance of chromatographic solvent gradient purifications

With significant advancement in the upstream processing technology, downstream processing of large bio-molecules is becoming the bottle-neck in the production chain. To face this challenge, design and development of efficient separation processes has become crucial. As a step towards boosting the performance of a chromatographic separation process through improved design, we investigated the potential of recycling as a process option. The most important advantage of recycling is that it can be implemented in an existing batch system without any major investment and consultation. Although impure products are recycled in industries, it is done as additional batch, and only then, when the recoverable product is valuable enough to surpass the loss of productivity in running the additional batches. In our study, on the other hand, it was found that a well-designed recycle can not only improve the yield, but also the productivity of a multi-component purification. A series of multiobjective optimization studies were carried out on multi-component separation to comprehend the role of recycling with reference to an industrially relevant problem, i.e. the chromatographic purification step of the production process of calcitonin.     

Antioxidant and antifungal activity of different extracts obtained from aerial parts of Inula crithmoides L.

The total phenolic content, antioxidant and antifungal activities of three Inula crithmoides extracts (n-hexane, methylene chloride and MeOH) were investigated. The methanolic extract showed the highest total phenolic content. In the DPPH assay, the methanolic and hexane extracts exhibited the highest DPPH-radical scavenging activity; in the 5-lipoxygenase assay, the hexane extract showed greater inhibitory effect with an IC₅₀ similar to that of Trolox and ascorbic acid. The antifungal activity of the methanolic extract revealed a higher activity against Phytophtora cryptogea and Alternaria solani.     

Role of catechin on collagen type I stability upon oxidation: a NMR approach

Abstract

The study focuses on the understanding, at molecular level, the mechanism of interaction between protein and flavonoids. Collagen and catechin interactions were investigated by NMR in solution and solid state. The effect of catechin on the stability of collagen to oxidation was also explored. Collagen was treated with two concentrations of catechin solutions. Oxidation was carried out by incubation of collagen solution with three oxidation systems: Fe(II)/H₂O₂, Cu(II)/H₂O₂, and NaOCl/H₂O₂. The effects of oxidation systems were evaluated by high resolution 1?D and 2?D proton spectroscopy and solid state NMR (¹³C CP MAS) experiments. Interactions between collagen and catechin preferentially occur between catechin B ring and the amino acids Pro and Hyp of collagen. Results showed that both iron and copper oxidation systems were able to interact with collagen by site specific attack. Moreover, catechin protects collagen proline from oxidation by metal/H₂O₂ systems, preventing copper and iron approach to collagene molecule;this behaviour was more evident for the copper/H₂O₂ system.     

Rewiring cellular metabolism for heterologous biosynthesis of Taxol

Abstract

Taxol is one of the anticancer drugs synthesized naturally in the evergreen Taxus brevifolia forest tree belonging to the yew family (Taxaceae) growing on the Pacific. There are reportedly evidence for treating ovarian, breast and lung cancers through this drug given its unique structural and functional features. Extraction of this drug from yew trees bark is one of the most common ways of producing this drug, but 3000 trees are needed to obtain a kilogram of Taxol. Hence, further attention has recently been attracted to the metabolic engineering strategies, including, engineering cellular metabolism of microorganisms and their optimization. Accordingly, the present paper article was aimed to review recent advances in elevating the production and commercialization of Taxol through metabolic engineering techniques.     

A new approach for the synthesis of K-free nickel hexacyanoferrate

A Ni, Al hydrotalcite-like compound (Htlc) has been proven an useful host material for an alternative synthesis of a K⁺-free mixed hexacyanoferrate Ni_1.5Fe^III(CN)₆, which is very difficult to obtain in bulk. The first stage of the procedure consists in the intercalation of hexacyanoferrate(III) inside the Htlc structure. The intercalated Htlc has been treated with a NiNO₃ solution. The obtained material has been characterized by XRD, XAS Raman and FT-IR spectroscopy. The voltammetric response of the compound obtained after the complete solubilization of the Htlc host shows a typical fingerprint of nickel hexacyanoferrate material with a very low level of potassium. Elemental analysis confirmed the absence of K⁺ and thus the occurrence of K⁺-free nickel hexacyanoferrate (14% yield).