Heavy Atom Substitution Research Articles

Pure Rotational Spectrum and Ring Inversion Tunnelling of Silacyclobutane

The ground state pure rotational spectrum of silacyclobutane (SCB) (c-SiH(2)C(3)H(6)) has been investigated using both Fourier transform microwave (FTMW) and chirped pulse Fourier transform microwave (cp-FTMW) spectroscopies. Spectra of the (13)C, (29)Si, and (30)Si singly substituted isotopologues, in natural abundance, were recorded in the 6-24 GHz region along with those of the normal species. The ring inversion tunnelling splitting in the ground vibrational state was resolved and analyzed to determine the energy splitting of the two states: 75.7260(19) MHz. Structural analysis based on heavy atom substitution provided accurate geometric parameters including the bond lengths, bond angles, and ring puckering angle of the SCB ring backbone.

Pure rotational spectrum and structural determination of silacyclopentane

The ground state pure rotational spectrum of silacyclopentane (SCP) has been investigated using both Fourier Transform Microwave (FTMW) and chirped pulse Fourier Transform Microwave (cp-FTMW) spectroscopies. In addition to the parent species, the spectra of the 13C, 29Si and 30Si singly-substituted isotopologues were recorded in the 6–24 GHz region in natural abundance. Structural analysis confirms that the ground state has C 2 symmetry and the geometric parameters determined based on heavy atom substitution include the bond distances, bond angles and dihedral angles of the SCP ring backbone.

Heavy Atom Substitution Effects in Non-Aromatic Ionic Liquids: Ultrafast Dynamics and Physical Properties

In this study, we have investigated the heavy atom substitution effects on the ultrafast dynamics in nonaromatic cation-based ionic liquids, as well as the static physical properties such as shear viscosity, surface tension, glass transition temperature, and melting point. Phosphonium-based ionic liquids show lower shear viscosities and lower glass transition temperatures than their corresponding ammonium-based ionic liquids. We have also examined the substitution of a (2-ethoxyethoxy)ethyl group for an octyl group in ammonium and phosphonium cations and found that the (2-ethoxyethoxy)ethyl group reduces the shear viscosity and increases the surface tension. From the results of the ultrafast dynamics, including intra- and interionic vibrations and reorientational relaxation in the ammonium- and phosphonium-based ionic liquids measured by means of femtosecond optically heterodyne-detected Raman-induced Kerr spectroscopy, we have found that the first moment of low-frequency Kerr spectrum, omitting the contributions of clear intraionic vibrational modes, correlates to the square root of surface tension divided by density. This fact indicates that heavy atom substitution in ionic liquids provides a weaker interionic interaction arising from the larger ionic volume. On the other hand, the ether group in the cations gives the stronger interionic interaction but with a more flexible and/or less segregated nature in the ILs than the alkyl group.

Determination of the Structure of Cyclopentene Oxide and the Argon−Cyclopentene Oxide van der Waals Complex

Rotational spectra of cyclopentene oxide and the argon-cyclopentene oxide van der Waals complex were studied using pulsed-jet Fabry-Perot Fourier transform microwave (FTMW) spectroscopy. Spectra of the parent along with those of the (13)C and (18)O singly substituted isotopologues, in natural abundance, of the monomer and of the complex were measured in the frequency region of 5-26.5 GHz. The complete heavy atom substitution structure was determined for the monomer and complex. The boat structure for cyclopentene oxide was confirmed with naturally abundant (13)C and (18)O isotopes. For the argon cyclopentene oxide complex, both a and b-type transitions were observed and the rotational constants for the all-(12)C (16)O isotopologue were determined to be A = 3268.254(2), B = 993.345(1), and C = 950.430(9) MHz. The r(0) coordinates of the argon in the principal axis system of cyclopentene oxide are a = 0.27, b = 0.42, and c = 3.91 A, such that the argon is exo to the boat of the ring and on the opposite side of the ring from the oxygen and is 0.42 A off to the side and 0.27 A from the center of mass toward the back end of the ring (again away from the oxygen). Large amplitude van der Waals bending vibrations require an averaging model to account for differences between the observed complex and monomer planar moments of inertia.

A dual-emissive-materials design concept enables tumour hypoxia imaging

Luminescent materials are widely used for imaging and sensing owing to their high sensitivity, rapid response and facile detection by many optical technologies. Typically materials must be chemically tailored to achieve intense, photostable fluorescence, oxygen-sensitive phosphorescence or dual emission for ratiometric sensing, often by blending two dyes in a matrix. Dual-emissive materials combining all of these features in one easily tunable molecular platform are desirable, but when fluorescence and phosphorescence originate from the same dye, it can be challenging to vary relative fluorescence/phosphorescence intensities for practical sensing applications. Heavy-atom substitution alone increases phosphorescence by a given, not variable amount. Here, we report a strategy for modulating fluorescence/phosphorescence for a single-component, dual-emissive, iodide-substituted difluoroboron dibenzoylmethane-poly(lactic acid) (BF(2)dbm(I)PLA) solid-state sensor material. This is accomplished through systematic variation of the PLA chain length in controlled solvent-free lactide polymerization combined with heavy-atom substitution. We demonstrate the versatility of this approach by showing that films made from low-molecular-weight BF(2)dbm(I)PLA with weak fluorescence and strong phosphorescence are promising as 'turn on' sensors for aerodynamics applications, and that nanoparticles fabricated from a higher-molecular-weight polymer with balanced fluorescence and phosphorescence intensities serve as ratiometric tumour hypoxia imaging agents.

Atom Substitution Effects of [XF6]− in Ionic Liquids. 1. Experimental Study

We have investigated the interionic vibrational dynamics of 1-butyl-3-methylimidazolium cation ([BMIm]+) based ionic liquids with the anions of [PF6]-, [AsF6]-, and [SbF6]- as well as the static physical properties, such as shear viscosity and liquid density. Shear viscosity for the ionic liquids becomes lower with the heavier atom anion: [BMIm][PF6]>[BMIm][AsF6]>[BMIm][SbF6]. This tendency for heavy atom substitution for the anion results from weaker interionic interaction caused by larger anion volume. Femtosecond optically heterodyne-detected Raman-induced Kerr effect spectroscopy has been used to observe the interionic vibrational dynamics of ionic liquids. The interionic vibration in the frequency region of less than 50 cm(-1) clearly shows the heavy atom substitution effect; that is, the heavy atom substitution of [XF6]- critically affects the interaction-induced motion. The forthcoming paper will further provide the molecular-level insights of the heavy atom substitution effect of the [XF6]- anion on the interionic dynamics and interaction for the three ionic liquids by a molecular dynamics simulation approach.

Photosensitization of Ruthenium Nitrosyls to Red Light with an Isoelectronic Series of Heavy-Atom Chromophores: Experimental and Density Functional Theory Studies on the Effects of O-, S- and Se-Substituted Coordinated Dyes

Three ruthenium nitrosyl-dye conjugates, namely, [((OMe)(2)bQb)Ru(NO)(Resf)] (RuNO-Resf), [((OMe)(2)bQb)Ru(NO)(Thnl)] (RuNO-Thnl), and [((OMe)(2)bQb)Ru(NO)(Seln)] (RuNO-Seln) have been synthesized using the tetradentate N4 dicarboxamido ligand H(2)(OMe)(2)bQb. Each nitrosyl of this series is conjugated to a phenoxazine-type heterotricyclic chromophore which has been systematically varied in a central position to test the effects of "heavy-atom" substitution (O = Resorufin; S = Thionol; Se = Selenophore) in photosensitization. The structure of the chloride-bound precursor {Ru-NO}(6) nitrosyl [((OMe)(2)bQb)Ru(NO)(Cl)] (RuNO-Cl) and three nitrosyl-dye conjugates, namely, RuNO-Resf, RuNO-Thnl and RuNO-Seln, have been determined by X-ray crystallography. All three nitrosyl-dye conjugates exhibit sharp (1)H NMR spectra (S = 0 ground state) and nu(NO) stretches in the IR spectrum in the region 1825-1855 cm(-1), typical of {Ru-NO}(6) nitrosyls. The presence of a heavy atom in the bound dye gives rise to a systematic red-shift in the electronic absorption spectrum, shifting from RuNO-Resf (lambda(max) = 500 nm) to RuNO-Thnl (lambda(max) = 530 nm) to RuNO-Seln (lambda(max) = 535 nm). Results of careful measurements with monochromatic light sources indicate that heavy-atom substitution in the coordinated dye makes the resulting nitrosyl-dye conjugates more susceptible to light of longer wavelength (lower energy). Density functional theory (DFT) calculations on RuNO-Cl, RuNO-Resf, RuNO-Thnl, and RuNO-Seln have been performed to gain insight into the electronic structure of the {dye-Ru-NO} frame and the nature of transition(s) that sensitizes these conjugates to lights of longer wavelengths and promote NO photolability. Results of this study provide an explanation for the sensitization observed in our strategy of direct attachment of dye molecules to {Ru-NO}(6) nitrosyls. This strategy could lead to eventual isolation of designed metal nitrosyls that are sensitive to red- or near-infrared light and hence potential photodynamic therapy (PDT) agents for treatment of malignancies with high doses of NO.

Photoreactivity of psoralen derivatives in micelles: The roles of hydrophobicity and heavy atom substitution

Intersystem crossing quantum yields of two psoralen derivatives, bromopsoralen (BrMOP) and hexylpsoralen (8-HOP) were measured in ethanol and water by means of laser flash photolysis. Compared to 8-methoxypsoralen (8-MOP), the triplet quantum yields of BrMOP and 8-HOP in ethanol are increased by a factor of 5 and 30, respectively, while BrMOP in aqueous solution shows a twofold enhancement with respect to 8-MOP. Radical cations and hydrated electrons were generated by photoionization in micellar solution upon excitation at 266 nm. A nonlinear relationship between transient yield and photon fluence was obtained for each compound, indicating that a two-photon mechanism is predominant in the photoionization of the sensitizers. The photoionization efficiencies are significantly higher in anionic sodium dodecyl sulfate (SDS) than in cationic cetyltrimethylammonium bromide (CTAB) micelles, reflecting the influence of micelle charge on the efficiency of the separation of the photoproduced charge carriers. The photoionization efficiencies of 8-HOP and 8-MOP are similar. It is concluded that the intersystem crossing properties of BrMOP show a substantial heavy atom effect, whereas the effects of hydrophobic substitution on photoionization efficiency are minor.

Synthesis, characterization and third-order nonlinear optical properties of bromo[tri-α-(2,4-dimethyl-3-pentyloxy)subphthalocyanine]boron complex

A new subphthalocyanine complex, bromo[tri-α-(2,4-dimethyl-3-pentyloxy)subphthalocyanine]boron, has been synthesized and characterized by elemental analysis, MALDI-TOF-MS, FT-IR and UV–vis spectroscopy. Its third-order nonlinear optical (NLO) properties in ethanol solution have been studied by Z-scan technique using 8 ns laser pulses at 532 nm. The results reveal that the new complex exhibits strong NLO absorption effect ( α 2 = 3.7 × 10 −10 m W −1) and self-focusing refractive performance ( n 2 = 2.1 × 10 −17 m 2 W −1). The effective third-order NLO susceptibility ( χ (3)) and the molecular second-order hyperpolarizability ( γ) value were calculated to be 1.12 × 10 −11 and ∼6.8 × 10 −28 esu, respectively. All of the values are comparable to those of the reported good NLO materials. In addition, the effects of cone-shaped molecular structure and axially heavy-atom (Br) substitution on third-order NLO properties are discussed.

Molecular Basis of Intramolecular Electron Transfer in Sulfite-oxidizing Enzymes Is Revealed by High Resolution Structure of a Heterodimeric Complex of the Catalytic Molybdopterin Subunit and a c-Type Cytochrome Subunit

Sulfite-oxidizing molybdoenzymes convert the highly reactive and therefore toxic sulfite to sulfate and have been identified in insects, animals, plants, and bacteria. Although the well studied enzymes from higher animals serve to detoxify sulfite that arises from the catabolism of sulfur-containing amino acids, the bacterial enzymes have a central role in converting sulfite formed during dissimilatory oxidation of reduced sulfur compounds. Here we describe the structure of the Starkeya novella sulfite dehydrogenase, a heterodimeric complex of the catalytic molybdopterin subunit and a c-type cytochrome subunit, that reveals the molecular mechanism of intramolecular electron transfer in sulfite-oxidizing enzymes. The close approach of the two redox centers in the protein complex (Mo-Fe distance 16.6 A) allows for rapid electron transfer via tunnelling or aided by the protein environment. The high resolution structure of the complex has allowed the identification of potential through-bond pathways for electron transfer including a direct link via Arg-55A and/or an aromatic-mediated pathway. A potential site of electron transfer to an external acceptor cytochrome c was also identified on the SorB subunit on the opposite side to the interaction with the catalytic SorA subunit.

Third-order nonlinear optical properties of bromo［tri-α-(2,4-dimethyl-3-pentyloxy) subphthalocyanine］ boron

The third-order nonlinear optical properties of a new subphthalocyanine complexe (bromo［tri-α-(2,4-dimethyl-3-pentyloxy) subphthalocyanine］ boron) was studied by Z-scan using 8ns laser pulses at 532nm. It was found that the compound shows a strong reverse saturation absorption (β=3.7×10-10 m/W) and nonlinear self-focusing refraction effects (n2=7.2×10-11 esu). The third-order nonlinear susceptibility (χ(3)) is 1.1×10-11esu.The effects of cone-chaped molecular structure and axially heavy-atom (Br) substitution on third-order nonlinear optical properties are also discussed.

A method for studying optical anisotropy of polymers as a function of molar mass.

Optical properties of polymers are extremely important in many end-use applications, as is the ability of anisotropic polymers to depolarize incident radiation. To date, most light-scattering studies of the optical anisotropy of macromolecules have dealt with the bulk state or measured ensemble properties of dilute solutions. Here, we introduce a method to determine the optical anisotropy as a continuous function of molar mass. By direct, on-line coupling of size-exclusion chromatography and depolarization multiangle light scattering (SEC/D-MALS), molar mass averages, polydispersities, molar mass distributions, and the distribution of the optical anisotropy as a function of molar mass may all be determined. To quantify the anisotropy, it has been expressed in terms of the Cabannes factor, thus permitting the Rayleigh ratio necessary for light-scattering calculations to be corrected for anisotropy. The effects of tacticity, heavy atom substitution on the main chain, and chain helicity on the depolarization behavior of polymers have been studied using atactic and isotactic PMMA; atactic and brominated PS; and the semiflexible polypeptide PBLG, which maintains an extended structure in solution. An introduction to the theory of SEC/D-MALS is given.

Determination of the kinetic parameters of radical pairs with heavy atom substitutions in micellar solution by optical detected × and Ku band ESR

A study is reported of the dynamics of radical pairs formed by the photochemical reaction of benzophenone and its heavy atom substitutions, dichlorobenzophenone and bromobenzophe-none, in a sodium dodecylsulphate micellar solution. Changes were observed in the time profiles of the transient absorptions and in the yields of the escaping radicals induced by the irradiation of an × (9.15 GHz) or Ku band (17.44 GHz) microwave short pulse. From these experiments, the hydrogen abstraction reaction rates, the recombination rates of the singlet radical pairs, the relaxation rates, the escape rates, the decay rates of the radical pairs without the external magnetic field, and the intersystem recombination rates due to the spin-orbit coupling were determined.

Vibrational Mechanism for Primary Charge Separation in the Reaction Center of Rhodobacter Sphaeroides

Geometry, reorganization energy, and vibrational and electronic spectra of pigment molecules in bacterial photosynthetic reaction centers (Rhodobacter sphaeroides) are determined using quantum chemical methods. B3LYP calculations on a slightly truncated form of bacteriochlorophyll a give vibrational modes at 23, 40, 64, and 128 cm-1, which we conclude correspond to those seen in resonance Raman (RR) spectra of reaction centers with labeled cofactor atoms, and, as oscillations, in optical transient spectra. On heavy atom substitution at the axial imidazole connection to the protein, a mode with considerable contribution of bending deformations of the whole imidazole is transformed to predominantly rocking modes of the whole macrocycle at 10 cm-1. Other modes, with significant character of out-of-plane, torsion, and in-plane motion of the acetyl side group of ring I, are less changed. We show that there is a connection between the mentioned modes, particularly the torsion mode of the acetyl group of ring I,...

14N/15N Isotope Effect on the Electron Transfer Process betweenN,N,N‘,N‘-Tetramethyl-p-phenylenediamine and Wurster's Blue

Appreciable 14N/15N equilibrium isotope effect has been observed for the electron-transfer process between N,N,N‘,N‘-tetramethyl-p-phenylenediamine (TMPD) and its radical cation perchlorate (TMPD+•ClCO4-, Wurster's blue). The equilibrium constant for the reaction, TMPD + [15N2]TMPD+• ⇌ TMPD+• + [15N2]TMPD, was determined to be 0.85 ± 0.05 at 25 °C in acetonitrile by electron spin resonance (ESR) analysis of the line-broadening effect of Wurster's blue in the presence of its parent neutral molecule. Redox potentials of TMPD and [15N2]TMPD were determined by cyclic voltammetry to be E° = 0.107 and 0.103 ± 0.002 V vs SCE respectively, corresponding to K = 0.86 ± 0.06 for the reaction. Comparison of the infrared and Raman spectra of TMPD, [15N2]TMPD and their radical cations revealed significant vibrational frequency shifts caused by the heavy-atom substitution and radical cation formation, from which the free energy change for the electron-transfer process was estimated to be 300 J mol-1, corresponding to K = 0.89. These results demonstrate that 15N-substitution of TMPD decreases appreciably the ionization potential of the molecule, making it easier to lose an electron forming the corresponding radical cation in solution.

14N/15N and 12C/13C Equilibrium Isotope Effects on the Electron-Transfer Reaction between N-Methylphenothiazine and Its Radical Cation

Appreciable equilibrium isotope effects have been observed for electron-transfer process between N-methylphenothiazine (MPT) and the radical cation of its 15N- and/or N−13C-methyl-substituted analogues via electron spin resonance (ESR) line-broadening effect of the radical cation perchlorates in the presence of the corresponding parent neutral molecule. The equilibrium constants for the following electron-transfer processes were determined to be K1 = 1.19 ± 0.06, K2 = 1.17 ± 0.12, K3 = 1.06 ± 0.03, K4 = 1.06 ± 0.05, and K5 = 1.27 ± 0.14 respectively, in acetonitrile at ambient temperature: MPT + [15N]MPT•+ MPT•+ + [15N]MPT; [13C]MPT + [13C,15N]MPT•+ [13C]MPT•+ + [13C,15N]MPT; [15N]MPT + [13C,15N]MPT•+ [15N]MPT•+ + [13C,15N]MPT; MPT + [13C]MPT•+ MPT•+ + [13C]MPT; MPT + [13C,15N]MPT•+ MPT•+ + [13C,15N]MPT. In addition, infrared and Raman spectra of the N-methylphenothiazines and their radical cations were recorded and compared to assign the vibrational frequency shifts caused by the heavy-atom substitution and radical cation formation, from which the enthalpy changes of the electron-transfer processes were estimated. These results reveal that 15N- and/or 13C-substitution of methylphenothiazine increases the ionization potential of the molecule, making it more difficult to lose an electron to form the corresponding radical cation in solution.

Solution of the structure of the cofactor-binding fragment of CysB: a struggle against non-isomorphism.

The elucidation of the structure of CysB(88-324) by multiple isomorphous replacement (MIR) techniques was seriously delayed by problems encountered at every stage of the analysis. There was extensive non-isomorphism both between different native crystals and between native and heavy-atom-soaked crystals. The heavy-atom substitution was invariably weak and different soaking experiments frequently led to substitution at common sites. These correlated heavy-atom binding sites resulted in an overestimation of the phase information. Missing low-resolution reflections in the native data set, constituting only 2% of the total observations, reduced the power of density modification and phase refinement. Finally, the extensive dimer interface made it difficult to isolate a single molecule in the course of model building into the MIR maps. The power of maximum likelihood refinement (REFMAC) was exploited in solving the structure by means of iterative cycles of refinement of a partial model, initially comprising only 30% of the protein atoms in the final coordinate set. This technique, which uses experimental phases, can automatically discriminate the correct and incorrect parts of electron-density maps and give properly weighted combined phases which are better than the experimental or calculated ones. This allowed the model to be gradually extended by manual building into improved electron-density maps. A model generated in this way, containing just 50% of the protein atoms, proved good enough to find the transformations needed for multi-crystal averaging between different crystal forms. The averaging regime im-proved the phasing dramatically such that the complete model could be built. The problems, final solutions and some possible causes for the observed lack of isomorphism are discussed.

Successful flash-cooling of xenon-derivatized myoglobin crystals

This paper demonstrates for the first time a method for preparing cryocooled xenon-derivatized protein crystals. The method is based upon the hypothesis and subsequent observation that the diffusion of a xenon atom from a tight binding site following depressurization occurs on a timescale of minutes. We have observed significant changes in diffraction intensities from myoglobin crystals for up to 5 min following depressurization from 1 MPa of xenon. In accordance with this observation, a xenon-derivatized myoglobin crystal was cryocooled at ~95 K within 20 s of complete depressurization. A crystallographic data set was then collected to 2.0 A resolution and isomorphous and anomalous difference Patterson maps revealed the presence of a well ordered xenon site with an occupancy of approximately 0.5. Phasing statistics for this site were of good quality and demonstrate the practicality of this method. The ability to cryocool xenon-derivatized crystals will make this heavy-atom substitution method even more useful for single-isomorphous-replacement and multiple-isomorphous-replacement phasing of macromolecules.

14N/15N ISOTOPE EFFECT ON THE ELECTRON TRANSFER PROCESS BETWEEN PHENOTHIAZINE AND ITS RADICAL CATION

An appreciable equilibrium isotope effect has been observed for electron transfer from phenothiazine (PT) to the radical cation of its 15N-substituted analogue ([15N]PT+·), i.e. PT+[15N]PT+· ⇋ K PT+·+[15N]PT via electron paramagnetic resonance analysis of the mixed radical cations formed from mixing the [15N]phenothiazine radical cation hexachloroantimonate and phenothiazine in acetonitrile (K=0·77±0·10 at 25 °C), and by physical separation of the neutral phenothiazines from the radical cation salts in the equilibrium mixture (K=0·83±0·10 at 25 °C). Infrared and Raman spectra of [14N]- and [15N]phenothiazines and their radical cations were measured to assign the vibrational frequency shifts caused by the heavy-atom substitution and radical cation formation, which gave an estimate of the enthalpy change of 441·7 J mol−1 for the electron transfer process. These results reveal that 15N substitution of phenothiazine decreases appreciably the ionization potential of the molecule, making it easier to lose an electron to form the corresponding radical cation in solution. © 1997 by John Wiley & Sons, Ltd.

Selenium-regulated translation control of heterologous gene expression: Normal function of selenocysteine-substituted gene products

In eukaryotes, the synthesis of selenoproteins depends on an exogenous supply of selenium, required for synthesis of the novel amino acid, selenocysteine, and on the presence of a "selenium translation element" in the 3' untranslated region of mRNA. The selenium translation element is required to re-interpret the stop codon, UGA, as coding for selenocysteine incorporation and chain elongation. Messenger RNA lacking the selenium translation element and/or an inadequate selenium supply lead to chain termination at the UGA codon. We exploited these properties to provide direct translational control of protein(s) encoded by transfected cDNAs. Selenium-dependent translation of mRNA transcribed from target cDNA was conferred by mutation of an in-frame UGU, coding for cysteine, to UGA, coding for either selenocysteine or termination, then fusing the mutated coding region to a 3' untranslated region containing the selenium translation element of the human cellular glutathione peroxidase gene. In this study, the biological consequences of placing this novel amino acid in the polypeptide chain was examined with two proteins of known function: the rat growth hormone receptor and human thyroid hormone receptor beta 1. UGA (opal) mutant-STE fusion constructs of the cDNAs encoding these two polypeptides showed selenium-dependent expression and their selenoprotein products maintained normal ligand binding and signal transduction. Thus, integration of selenocysteine had little or no consequence on the functional activity of the opal mutants; however, opal mutants were expressed at lower levels than their wild-type counterparts in transient expression assays. The ability to integrate this novel amino acid at predetermined positions in a polypeptide chain provides selenium-dependent translational control to the expression of a wide variety of target genes, allows facile 75Se radioisotopic labeling of the heterologous proteins, and permits site-specific heavy atom substitution.