1-Naphthyl- and mesityltellurium(IV,II) derivatives of small bite chelating organic ligands: effect of steric bulk and intramolecular secondary bonding interaction on molecular geometry and supramolecular association

The synthesis and characterization of unsymmetric diorganotellurium compounds containing a sterically demanding I-naphthyl or
mesitylligand and a small bite chelating organic ligand capable of 1,4-Te···N(O) intramolecular interaction is described. The reaction
of ArTeCl₃ (Ar = I-C_lOH₇, Np; 2,4,6-Me₃C₆H_2' Mes) with (SB)HgCI [SB = the Schiff base, 2-(4,4'-N0₂C₆H₄CH=NC₆H₃-Me)] or a methyl ketone (RCOCH₃) afforded the corresponding dichlorides (SB)ArTeCI₂ (Ar = Np, 1Aa; Mes, 1Ba) or (RCOCH₂)ArTeCl₂ (Ar = Np; R = Ph (2Aa), Me (3Aa), Np (4Aa); Ar = Mes, R = Ph (2Ba)). Reduction of 1Aa and 1Ba by Na₂S₂0₅ readily gave the tellurides (SB)ArTe (Ar = Np (1A), Mes, (1B) but that of dichlorides derived from methylketones was complicated due to partial decomposition to tellurium powder and diarylditelluride (Ar₂Te₂), resulting in poor yields of the corresponding tellurides 2A, 2B and 3A. Oxidation of the isolated tellurides with S0₂Cl₂, Br₂ and I₂ yielded the corresponding dihalides. All the synthesized compounds have been characterized with the help of IR, ¹H, ^l3C, and ¹²⁵Te NMR and in the case of 2Aa, and 2Ba by X-ray crystallography. Appearance of only one ¹²⁵Te signal indicated that the unsymmetric derivatives were stable to disproportionation to symmetric species. Intramolecular 1,4-Te· . ·0 secondary bonding interactions (SBIs) are exhibited in the crystal structures of both the tellurium(IV) dichlorides, 2Aa, and 2Ba. Steric repulsion of the mesityl group in the latter dominates over lone pair-bond pair repulsion, resulting in significant widening of the equatorial C-Te-C angle. This appears to be responsible for the lack of Te· . ·CI involved supramolecular associations in the crystal structure of 2Ba.

Acylmethyl(aryl)tellurium(IV,II) derivatives : intramolecular secondary bonding and steric rigidity

Electrophilic substitution of acylmethanes (methyl ketones), RCOCH3 (R = i-Pr, 1; Et, 2; Me, 3) with aryltellurium trichlorides, ArTeCl3 (Ar = 1-C10H7, Np, A; 2,4,6-Me3C6H2, Mes, B; 4-MeOC6H4, Anisyl, C) under mild conditions affords the corresponding acylmethyl(aryl)tellurium dichlorides (RCOCH2)ArTeCl2. Reduction of the dichlorides, gives tellurides, (i-PrCOCH2)ArTe, 1A–1C, which give the corresponding dihalides, (i-PrCOCH2)ArTeX2 (X = Cl, 1Aa–1Ca; Br, 1Ab–1Cb; I, 1Ac–1Cc) when reacted in situ with SO2Cl2, Br2 or I2. The unsymmetric tellurides are labile towards disproportionation and attempts to obtain them lead to the isolation of Ar2Te2 except in the case of (i-PrCOCH2)MesTe ( 1B), which represents an interesting example of a kinetically stable aryl(alkyl)telluride. All the dihalomesityltellurium(IV) derivatives show separate 1H and 13C NMR signals for the ortho methyls irrespective of the sizes of R and X ligands. The telluride, 1B with free rotation about Te–C(mesityl) bond shows, like the unsymmetric diorganotellurium(IV) dihalides, only one 125Te NMR signal. The 1,4-chelating behavior of the acyl ligand among diorganotellurium(IV) compounds is inferred from the X-ray diffraction data for 1Aa, 1Ac, 1Ba, 1Bb, 1Ca and 1Cc which are indicative of the presence of intramolecular TeO secondary bonding interactions (SBIs) at least in the solid state. As a consequence, steric repulsion in case of the mesityltellurium(IV) derivatives, 1Ba and 1Bb, reaches the threshold so as to cause loss of two-fold rotational symmetry of the mesityl group about the Te–C(mesityl) bond axis. Intermolecular C–HO H-bonding interactions appears to stabilize such an orientation of the aryl ligand at least in the solid state.

Conformational analysis and design of cross-strand disulfides in antiparallel beta-sheets

Cross-strand disulfides bridge two cysteines in a registered pair of antiparallel beta-strands. A nonredundant data set comprising 5025 polypeptides containing 2311 disulfides was used to study cross-strand disulfides. Seventy-six cross-strand disulfides were found of which 75 and 1 occurred at non-hydrogen-bonded (NHB) and hydrogen-bonded (HB) registered pairs, respectively. Conformational analysis and modeling studies demonstrated that disulfide formation at HB pairs necessarily requires an extremely rare and positive chi(1) value for at least one of the cysteine residues. Disulfides at HB positions also have more unfavorable steric repulsion with the main chain. Thirteen pairs of disulfides were introduced in NHB and HB pairs in four model proteins: leucine binding protein (LBP), leucine, isoleucine, valine binding protein (LIVBP), maltose binding protein (MBP), and Top7. All mutants LIVBP T247C V331C showed disulfide formation either on purification, or on treatment with oxidants. Protein stability in both oxidized and reduced states of all mutants was measured. Relative to wild type, LBP and MBP mutants were destabilized with respect to chemical denaturation, although the sole exposed NHB LBP mutant showed an increase of 3.1 degrees C in T-m. All Top7 mutants were characterized for stability through guanidinium thiocyanate chemical denaturation. Both exposed and two of the three buried NHB mutants were appreciably stabilized. All four HB Top7 mutants were destabilized (Delta Delta G(0) = -3.3 to -6.7 kcal/mol). The data demonstrate that introduction of cross-strand disulfides at exposed NHB pairs is a robust method of improving protein stability. All four exposed Top7 disulfide mutants showed mild redox activity. Proteins 2011; 79: 244-260. (C) 2010 Wiley-Liss, Inc.

Contribution of solvent effect to the optical spectra of polyanilines: has it been underestimated

The coefficient of thermochromism of polyaniline solutions has been found to be solvent dependent and the solvent effect is not negligible. Hence, thermochromism of polyaniline solutions cannot be explained solely on the basis of conformational change induced by a change in temperature. Further, comparison of the solvatochromism of polyaniline and polytoluidine shows a higher solvatochromic shift for the former. It implies that the higher energy associated with the exciton peak of polytoluidine is not due to the higher ring torsional angle induced by the higher steric repulsion of the methyl group, as widely accepted, but is due to its less solvatochromic red-shift as compared to polyaniline.

Bimetallic olefin polymerization catalysis : mechanisms and applications of proximal effects

This dissertation covers progress with bimetallic polymerization catalysts. The complexes we have designed were aimed at expanding the capabilities of homogeneous polymerization catalysts by taking advantage of multimetallic effects. Such effects were examined in group 4 and group 10 bimetallic complexes; proximity and steric repulsion were determined to be major factors in the effects observed.

Chapters 2 and 3 introduce the rigid p-terphenyl dinucleating framework utilized in most of this thesis. The permethylation of the central arene allows for the separation of syn and anti atropisomers of the terphenyl compounds. Kinetic studies were carried out to examine the isomerization of the dinucleating bis(salicylaldimine) ligand precursors. Metallation of the syn and anti bis(salicylaldimine)s using Ni(Me)2(tmeda) and excess pyridine afforded dinickel bisphenoxyiminato complexes with a methyl and a pyridyl ligand on each nickel. The syn and anti atropisomers of the dinickel complexes were structurally characterized and utilized in ethylene and ethylene/α-olefin polymerizations. Monometallic analogues were also synthesized and tested for polymerization activity. Ethylene polymerizations were performed in the presence of primary, secondary, and tertiary amines – additives that generally deactivate nickel polymerization catalysts. Inhibition of this deactivation was observed with the syn atropisomer of the bimetallic species, but not with the anti or monometallic analogues. A mechanism was proposed wherein steric repulsion of the substituents on proximal nickel centers disfavors simultaneous ligation of base to both of the metal centers. The bimetallic effect has been explored with respect to size and binding ability of the added base.

Chapter 4 presents the optimization of the bisphenoxyimine ligand synthesis and synthesis of syn and anti m-terphenyl analogues. Metallation with NiClMe(PMe₃)₂ yielded phosphine-ligated dinickel complexes, which have been structurally characterized. Ethylene/1-hexene copolymerizations in the presence of amines using Ni(COD)₂ as a phosphine scavenger showed significantly improved activity relative to the pyridine-ligated analogues. Incorporation of amino olefins in copolymerizations with ethylene was accomplished, and a mechanism was proposed based on proximal effects. Copolymerization trials with a variety of amino olefins and ethylene/1-hexene/amino olefin terpolymerizations were completed.

Early transition metal complexes based on the rigid p-terphenyl framework were designed with a variety of donor sets (Chapter 5 and Appendix B). Chapter 5 details the use of syn dizirconium di[amine bis(phenolate)] complexes for isoselective 1-hexene and propylene homopolymerizations. Ligand variation and monometallic complexes were studied to determine the origin of tacticity control. A mechanistic proposal was presented based on the symmetry at zirconium and the steric effects of the proximal metal center. Appendix B covers additional studies of bimetallic early transition metal complexes based on the p-terphenyl. Dititanium, dizirconium, and asymmetric complexes with bisphenoxyiminato ligands and derivatives thereof were targeted. Progress toward the synthesis of these complexes is described along with preliminary polymerization data. 1-hexene/diene copolymerizations and attempted polymerizations in the presence of ethers and esters with the syn dizirconium di[amine bis(phenolate)] complexes demonstrate the potential for further applications of this system in catalysis.

Appendix A includes work toward palladium catalysts for insertion polymerization of polar monomers. These complexes were based on dioxime and diimine frameworks with the intent of binding Lewis acidic metals at the oxime oxygens, at pendant phenolic donors, or at pendant aminediol moieties. The synthesis and structural characterization of a number of palladium and Lewis acid complexes is presented. Due to the instability of the desired species, efforts toward isolation of the desired complexes proved unsuccessful, though preliminary ethylene/methyl acrylate copolymerizations using in situ activation of the palladium species were attempted.

INVESTIGATION OF THE GROWN DIAMOND (100) SURFACE USING HIGH-RESOLUTION ELECTRON-ENERGY LOSS SPECTROSCOPY

The diamond (100) facets deposited at initial 1.0% CH4 have been investigated using high resolution electron energy loss spectroscopy (HREELS). The diamond (100) facets grown at 800-degrees-C are terminated by CH2 radicals, and there is no detectable frequency shift compared with the characteristic frequencies of molecular subgroup CH2. Beside the CH2 vibration loss, CH bend loss (at 140 meV) of locally monohydrogenated dimer is detected for the diamond (100) facets grown at 1000-degrees-C. Dosing the (100) facets grown at 800-degrees-C with atomic hydrogen at 1*10(-6) mbar, the loss peak at 140 meV appears. It is suggested that there are enough separately vacant sites and uniformly dispersed monohydrogenated dimers on (100) facets. This structure relaxes the steric repulsion between the adjacent hydrogen atoms during the diamond (100) surface growth.

MOLECULAR-GEOMETRY AND CHAIN ENTANGLEMENT - PARAMETERS FOR THE TUBE MODEL

The tube diameter in the reptation model is the distance between a given chain segment and its nearest segment in adjacent chains. This dimension is thus related to the cross-sectional area of polymer chains and the nearest approach among chains, without effects of thermal fluctuation and steric repulsion. Prior calculated tube diameters are much larger, about 5 times, than the actual chain cross-sectional areas. This is ascribed to the local freedom required for mutual rearrangement among neighboring chain segments. This tube diameter concept seems to us to infer a relationship to the corresponding entanglement spacing. Indeed, we report here that the critical molecular weight, M(c), for the onset of entanglements is found to be M(c) = 28 A/([R2]0/M), where A is the chain cross-sectional area and [R2]0 the mean-square end-to-end distance of a freely jointed chain of molecular weight M. The new, computed relationship between the critical number of backbone atoms for entanglement and the chain cross-sectional area of polymers, N(c) = A0,44, is concordant with the cross-sectional area of polymer chains being the parameter controlling the critical entanglement number of backbone atoms of flexible polymers.

Photochromic dithienylethene derivatives containing Ru(II) or Os(II) metal units. Sensitized photocyclization from a triplet state

Efficient photocyclization from a low-lying triplet state is reported for a photochromic dithienylperfluorocyclopentene with Ru(bpy)(3) units attached via a phenylene linker to the thiophene rings. The ring-closure reaction in the nanosecond domain is sensitized by the metal complexes. Upon photoexcitation into the lowest Ru-to-bpy (MLCT)-M-1 state followed by intersystem crossing to emitting (MLCT)-M-3 states, photoreactive (IL)-I-3 states are populated by an efficient energy-transfer process. The involvement of these (IL)-I-3 states explains the quantum yield of the photocyclization, which is independent of the excitation wavelength but decreases strongly in the presence of dioxygen. This behavior differs substantially from the photocyclization of the nonemissive dithienylperfluorocyclopentene free ligand, which occurs from the lowest (IL)-I-1 state on a picosecond time scale and is insensitive to oxygen quenching. Cyclic voltammetric studies have also been performed to gain further insight into the energetics of the system. The very high photocyclization quantum yields, far above 0.5 in both cases, are ascribed to the strong steric repulsion between the bulky substituents on the dithienylperfluorocyclopentene bridge bearing the chelating bipyridine sites or the Ru(bpy)(3) moieties, forcing the system to adopt nearly exclusively the reactive antiparallel conformation. In contrast, replacement of both Ru(II) centers by Os(II) completely prevents the photocyclization reaction upon light excitation into the low-lying Os-to-bpy (MLCT)-M-1 state. The photoreaction can only be triggered by optical population of the higher lying (IL)-I-1 excited state of the central photochromic unit, but its yield is low due to efficient energy transfer to the luminescent lowest (MLCT)-M-3 state.

Colloid probe AFM study of thermal collapse and protein interactions of poly(N-isopropylacrylamide) coatings

Graft coatings of poly(N-isopropylacrylamide) (pNIPAM) are of considerable interest for the reversible control of bio-interfacial interactions. In this study, graft coatings were prepared by free radical polymerisation from surface-bound polymerisable groups, on silicon wafers and quartz crystal microbalance (QCM) sensors. QCM with dissipation monitoring showed a gradual, extended phase change as the temperature increased. Colloid probe atomic force microscopy (CP-AFM) revealed a marked change in the compressibility of the coating below and above the lower critical solution temperature (LCST). Force curves showed an approximate 9-fold reduction in thickness between 24 °C and 38 °C, yet the collapsed coating at 38 °C still had a thickness significantly higher than the ellipsometrically determined dry thickness, indicating a residual extent of hydration above the LCST. At all temperatures, interaction force curves showed steric repulsion, though over different distances. There was little hysteresis between approach and retract force curves, which is evidence for almost instantaneous relaxation of the coating upon decompression. CP-AFM using a probe coated with bovine serum albumin (BSA) showed repulsive interactions with little approach/retraction hysteresis below the LCST, indicating lack of adhesion between the pNIPAM coating and the BSA-coated probe. In contrast, above the LCST the force curves on retraction were characteristic of adhesion, while the approach curves were still repulsive, and the adhesion increased in strength as the temperature was increased further beyond the LCST. Thus, QCM-D and CP-AFM data correlated well in showing a gradual nature of the phase transition and a concomitant gradual change in the interaction force with BSA.

Structure and characteristics of milled silk particles

This study examined the structure, thermal property, and ion adsorption of silk particles. The particles were prepared by attritor-bead mill combination, using alkaline (pH10) charge repulsion and surfactant steric repulsion methods. Both methods produced particles with a dominant β-sheet structure, similar to the silk fibre. There was no significant difference in the decomposition temperatures for either the silk fibre or the micro/nano silk particles. An important finding from this study is clear evidence of reduction of amorphous content during the final stage of powdering using the bead mill. As a result, despite reduction in β-sheet crystallites with the progressive milling, the relative β-sheet content actually increased during this process. However, intermolecular forces between the β-sheets reduced significantly and hence the XRD results showed significant reduction in crystallinity in nano silk particles but crystal forming segments remained with β-sheet conformations after milling. The structural change influenced the ion-adsorption property where particle-size reduction resulted in a significant increase in both the rate and volume of HCrO4- adsorption. © 2014 Elsevier B.V.

Amorphous ZrF4-a molecular dynamics study

Using an effective two-body interaction potential, a molecular dynamics study of the structural properties of amorphous ZrF4 phase is presented. The effective pair potential includes steric repulsion, Coulomb interaction due to charge transfer, and charge-dipole interaction due to the large electronic polarizability of anions. The results for structural correlations, such as pair distribution functions, coordination numbers, and bond angle distributions are presented. Excellent agreement is obtained by comparing experimental X-ray diffraction and the simulated static X-ray structure factor. © 1993.

Surface layer formation in polymer melts and in solutions

In this work the surface layer formation in polymer melts and in polymer solutions have been investigated with the atomic force microscope (AFM). In polymer melts, the formation of an immobile surface layer results in a steric repulsion, which can be measured by the AFM. From former work it is know, that polydimethyl siloxane (PDMS) forms a stable surface layer for molecular weights above 12 kDa. In the present thesis, polyisoprene (PI) was investigated apart from PDMS, by a)measuring the steric surface interactions and b)measuring the surface slip in hydrodynamic experiments. If a polymer flows over a surface, the flow velocity at the surface is larger then zero. If case of a surface layer formation the flow plane changes to the top of the adsorbed layer and the surface slip is reduced to zero. By measuring the surface slip in hydrodynamic experiments, it is therefore possible to determine the presence of a stable surface layer. The results show no stable repulsion for PI and only a small decrease of the surface slip. This indicates that PI does not form a stable surface layer, but is only adsorbed weakly to the surface. Furthermore for 8 kDa PDMS the timescale of the formation of a surface layer was investigated by changing themaximal force the tip applied to the surface. With a repulsive force present, applying a higher force than 15 nN resulted in a destruction of the surface layer, indicated by attractive forces. Reducing the applied force below 15 nN then resulted in an increase of the repulsion to the former state during one minute, thus indicating that a surface layer can be formed within one minute even under the influence of continuous measurements. As a next step, mixtures of two PDMS homopolymers with different chain lengths have been investigated. The aim was to verify theoretical predictions that shorter chains should predominate at the surface due to their smaller loss in conformational entropy. The measurements where done in dependence of the volume fractions of short and long chain PMDS. The results confirmed the short chain dominance for all mixtures with less then 90 vol.% long chain PDMS. Surface layer formation in solution was investigated for superplasticizers which are industrially used as an additive to cement. They change the surface interaction between the cement grains from attractive to repulsive and the freshlymixed cement paste therefore becomes liquid. The aimin this part of the thesis was, to investigate cement particle interactions in a close to real environment. Therefore calcium silicate hydrate phases have been precipitated onto an AFM tip and onto a calcite crystal and the interaction between these surfaces have beenmeasured with and without addition of superplasticizers. The measurements confirmed the change from attraction to repulsion upon addition of superplasticizers. The repulsive steric interaction increased with the length of the sidechain of the superplasticizer, and the dependence of the range of the steric interactions on the sidechain length indicated that the sidechains are in a coiled conformation.

Direct observation of the enhancement of noncooperative protein self-assembly by macromolecular crowding: Indefinite linear self-association of bacterial cell division protein FtsZ

Recent measurements of sedimentation equilibrium and sedimentation velocity have shown that the bacterial cell division protein FtsZ self-associates to form indefinitely long rod-like linear aggregates in the presence of GDP and Mg2+. In the present study, the newly developed technique of non-ideal tracer sedimentation equilibrium was used to measure the effect of high concentrations—up to 150 g/liter—of each of two inert “crowder” proteins, cyanmethemoglobin or BSA, on the thermodynamic activity and state of association of dilute FtsZ under conditions inhibiting (−Mg2+) and promoting (+Mg2+) FtsZ self-association. Analysis of equilibrium gradients of both FtsZ and crowder proteins indicates that, under the conditions of the present experiment, FtsZ interacts with each of the two crowder proteins essentially entirely via steric repulsion, which may be accounted for quantitatively by a simple model in which hemoglobin, albumin, and monomeric FtsZ are modeled as effective spherical hard particles, and each oligomeric species of FtsZ is modeled as an effective hard spherocylinder. The functional dependence of the sedimentation of FtsZ on the concentrations of FtsZ and either crowder indicates that, in the presence of high concentrations of crowder, both the weight-average degree of FtsZ self-association and the range of FtsZ oligomer sizes present in significant abundance are increased substantially.

Stereochemical and steric control of enzymatic glucuronidation : A rational approach for the design of novel Inhibitors for the human UDP-glucuronosyltransferase 2B7

The UDP-glucuronosyltransferases (UGTs) are enzymes of the phase II metabolic system. These enzymes catalyze the transfer of α-D-glucuronic acid from UDP-glucuronic acid to aglycones bearing nucleophilic groups affording exclusively their corresponding β-D-glucuronides to render lipophilic endobiotics and xenobiotics more water soluble. This detoxification pathway aids in the urinary and biliary excretion of lipophilic compounds thus preventing their accumulation to harmful levels. The aim of this study was to investigate the effect of stereochemical and steric features of substrates on the glucuronidation catalyzed by UGTs 2B7 and 2B17. Furthermore, this study relates to the design and synthesis of novel, selective inhibitors that display high affinity for the key enzyme involved in drug glucuronidation, UGT2B7. The starting point for the development of inhibitors was to assess the influence of the stereochemistry of substrates on the UGT-catalyzed glucuronidation reaction. A set of 28 enantiomerically pure alcohols was subjected to glucuronidation assays employing the human UGT isoforms 2B7 and 2B17. Both UGT enzymes displayed high stereoselectivity, favoring the glucuronidation of the (R)-enantiomers over their respective mirror-image compounds. The spatial arrangement of the hydroxy group of the substrate determined the rate of the UGT-catalyzed reaction. However, the affinity of the enantiomeric substrates to the enzymes was not significantly influenced by the spatial orientation of the nucleophilic hydroxy group. Based on these results, a rational approach for the design of inhibitors was developed by addressing the stereochemical features of substrate molecules. Further studies showed that the rate of the enzymatic glucuronidation of substrates was also highly dependent on the steric demand in vicinity of the nucleophilic hydroxy group. These findings provided a rational approach to turn high-affinity substrates into true UGT inhibitors by addressing stereochemical and steric features of substrate molecules. The tricyclic sesquiterpenols longifolol and isolongifolol were identified as high-affinity substrates which displayed high selectivity for the UGT isoform 2B7. These compounds served therefore as lead structures for the design of potent and selective inhibitors for UGT2B7. Selective and potent inhibitors were prepared by synthetically modifying the lead compounds longifolol and isolongifolol taking stereochemical and steric features into account. The best inhibitor of UGT2B7, β-phenyllongifolol, displayed an inhibition constant of 0.91 nM.

A laser flash photolysis study of pivalothiophenone triplets: steric and electronic effects in thione photoreaction kinetics

Upon laser pulse excitation (Aex = 532 nm) into the lowest-lying '(n,a*) band system, pivalothiophenones in benzene solutions give rise to short-lived triplets (Ama: = 325-335 nm, em: = (1 1-15) X lo3 M-' cm-I) with quantitative intersystem crossing efficiencies. The triplet yields decrease slightly (by 10-30%) upon changing A, to 308 nm (Le., upon excitation into S2). Kinetic data are presented for intrinsic triplet lifetimes, self-quenching, and quenching by oxygen, di-tert-butylnitroxy radical, and various reagents capable of interacting with the triplets via energy, electron, or hydrogen-atom transfer and by biradical formation (possibly leading to cycloaddition). The mechanisms of the quenching processes are discussed. Relative to rigid aromatic thiones, namely, xanthione and thiocoumarin, the interaction of pivalothiophenone triplets with most of the quenchers are kinetically inefficient. This is interpreted primarily as a manifestation of the steric crowding at positions a to the thiocarbonyl group.