Synthesis, Characterization, and Photophysical Studies of an Iron(III) Catecholate-Nitronylnitroxide Spin-Crossover Complex.

The synthesis and characterization of an Fe(III) catecholate-nitronylnitroxide (CAT-NN) complex (1-NN) that undergoes Fe(III) spin-crossover is described. Our aim is to determine whether the intraligand exchange coupling of the semiquinone-nitronylnitroxide Fe(II)(SQ-NN) excited state resulting from irradiation of the CAT → Fe(III) LMCT band would affect either the intrinsic photophysics or the iron spin-crossover event when compared to the complex lacking the nitronylnitroxide radical (1). X-ray crystallographic analysis provides bond lengths consistent with a ferric catecholate charge distribution. Mössbauer spectroscopy clearly demonstrates Fe(III) spin-crossover, hyperfine couplings, and a weak ferromagnetic Fe(III)-CAT-NN exchange, and spin-crossover is corroborated by variable-temperature magnetic susceptibility and electronic absorption studies. To explore the effect of the NN radical on photophysical processes, we conducted room-temperature transient absorption experiments. Upon excitation of the ligand-to-metal charge transfer band, an Fe(II)SQ state is populated and most likely undergoes fast intersystem crossing to the ligand field manifold, where it rapidly decays into a metastable low-spin Fe(III)CAT state, followed by repopulation of the high-spin Fe(III)CAT ground state. The decay components of 1-NN are slightly faster than those obtained for 1, perhaps due to the higher number of microstates present within the LMCT and LF manifolds for 1-NN. Although the effects of the NN radical are manifest in neither the spin-crossover nor the photophysics, our results lay the groundwork for future studies.

Mixed anion (phosphate/oxalate) bonding to iron(III) materials.

A novel phosphate/oxalate inorganic-organic hybrid material has been prepared to elucidate synthesis and bonding characteristics of iron(III) with both phosphate and organic matter (OM). Such mixed anion bonding of inorganic oxyanions and OM to iron(III) and aluminum(III) in environmental systems has been proposed but not proven, mainly because of the complexity of natural geochemical matrices. The compound reported here with the molecular formula of [C(3)H(12)N(2)](2)[Fe(5)(C(2)O(4))(2)(H(x)PO(4))(8)] (I) was hydrothermally synthesized and characterized by single crystal X-ray diffraction and X-ray absorption spectroscopy (XAS). In this new structure, Fe-O octahedra and P-O tetrahedra are connected by corner-sharing to form a 2-D network in the a-b plane. Oxalate anions cross-link these Fe-P layers constructing a 3-D anionic framework. A diprotonated structure-directing template, DAP (1,3-diaminopropane), resides in the oxalate layer of the structure and offsets the negative charge of the anionic framework. Iron K-edge XANES spectra confirmed that the iron in I is Fe(III). The crystal structure of I is used to successfully fit its Fe K-edge EXAFS spectrum, which exhibits spectral signatures that unambiguously identify iron-phosphate and iron-OM bonding. Such molecular spectroscopic features will be invaluable for the evaluation of complex environmental systems. Furthermore, syntheses demonstrated the critical role of the templating amine to mediate whether or not the iron(III) is reduced by the organic acid.

What do epidemiologists mean by 'population mixing'?

There is growing evidence that some chronic diseases are caused, or promoted, by infectious disease. 'Population mixing' has been used as a proxy for the range and dose of infectious agents circulating in a community. Given the speculation over the role of population mixing in many chronic diseases, we review the various methods used for measuring population mixing, and provide a classification of these. We recommend that authors fulfill two criteria in publications: measures are demonstrably associated with the putative risk factors for which population-mixing is acting as a proxy and fundamental characteristics of the chosen measures are clearly defined.

Entropic folding pathway of human epidermal growth factor explored by disulfide scrambling and amplified collective motion simulations.

Epidermal growth factor (EGF) regulates cell proliferation and differentiation by binding to the EGF receptor (EGFR) extra-cellular domains. Human EGF is a small, single-chain protein comprising three distinct loops (A, B, and C), which are connected by three disulfide bridges (Cys6-Cys20, Cys14-Cys31, and Cys33-Cys42). These disulfide bridges are essential for structural stability and biological activity. EGF was extensively studied by disulfide scrambling, an experimental technique for the conformational entrapment of intermediate states, which allows us to study the folding pathway of proteins containing disulfide bonds. The experimental results showed that there is a major 2-disulfide intermediate (denoted EGF-II) and that the native disulfide bonding pattern is less prevalent in one of the mutants. In this article, we investigated for the first time the solution conformations of wild-type EGF, EGF-II, and the mutant S9C through extensive molecular dynamics (MD) simulations in water using both the standard MD technique and a recently developed amplified-collective-motion (ACM) sampling method. Compared to standard MD simulations, we achieved a much more enhanced sampling by the ACM simulations, and the structures were sufficiently relaxed to estimate configurational entropies. The simulation results suggest a predominantly entropic folding pathway governed by the disorder of three functional loop regions. Although EGF-II exhibits two native disulfide bonds (Cys14-Cys31 and Cys33- Cys42), its large configurational entropy inhibits a direct transition to the native structure in the folding process. When Ser9 is mutated into Cys, a non-native disulfide bridge Cys9- Cys20 is slightly more favorable than the native Cys6-Cys20 because a less constrained N-terminus affords larger entropy. Isomers that are functionally less active also exhibit a more localized dynamics of the functional loop regions, which may suggest a possible mechanism for the modulation of EGF activity.

Is the urban excess in lung cancer in Scotland explained by patterns of smoking?

Numerous studies have shown that lung cancer rates are higher in urban than rural areas, controlling for differences in age and sex profiles. One explanation is that smoking rates are higher in urban areas, although it is not clear whether the variations in smoking behaviour fully account for the observed urban/rural gradient in lung cancer incidence. Indeed, some studies have demonstrated an excess of cases in urban areas, even controlling for smoking behaviour. However, previous studies have been hampered by the lack of small-area smoking estimates which are required if urban/rural variations are to be examined reliably. This paper considers whether there is an urban excess in lung cancer incidence in Scotland, a country with particularly high rates of the disease, for the period 1988-1991. First, we examine whether an urban excess exists in Scotland using Poisson probabilities and a cluster detection technique. Second, regression analysis was then used to test whether any urban excess in lung cancer incidence remained once smoking behaviour was controlled for, using smoking estimates calculated for small areas throughout Scotland. The results demonstrate that the rates of lung cancer were higher in urban areas and that all the significant clusters of cases of lung cancer were located in the large urban centres of Scotland. Smoking behaviour did account for much of this urban excess in lung cancer, although it did not explain the entire effect. These results suggest that there are urban effects that influence the incidence of lung cancer that are not explained entirely by smoking behaviour. Possible explanations include the variations in exposure to air pollution, occupational differences and the legacy of selective migration between urban and rural areas.

Examining the relationship between lung cancer and radon in small areas across Scotland.

Numerous studies have suggested that long-term exposure to radon gas may be an important cause of lung cancer, yet the precise effects are still not fully understood, especially in residential settings. This paper considers whether there is a relationship between the distribution of naturally occurring radon gas and lung cancer incidence in Scotland, for the period 1988-1991. We use regression analysis to test whether exposure to radon was a significant cause of lung cancer in Scotland, once smoking and other possible confounding factors were controlled for. The results demonstrate that for the population aged over 54, there was no significant relationship between radon exposure and lung cancer incidence. However, for those aged less than 55, lung cancer rates were significantly higher in places expected to have the highest levels of radon. These results suggest that more research is needed into the relationship between exposure to naturally occurring radon gas and lung cancer in Scotland, particularly among younger age groups.

Predicting smoking behaviour in census output areas across Scotland.

Spatially disaggregated surveys of smoking behaviour are rare and hence estimating the geography of the incidence of smoking is difficult. The main aim of this study is to develop a technique for estimating smoking probability for different age/sex groups in small areas across the whole of Scotland using information on smoking behaviour from the Scottish Household Survey. This is useful not only in its own right, but as an aid to studies of geographical variations in diseases such as lung cancer that, as a first step, need to control for smoking behaviour. The method developed uses individual-level characteristics from the Scottish Household Survey combined with a set of output area and pseudo-postcode sector measures from the 1991 census to model the probability of smoking. The parameters from this model are then used to make smoking predictions by age and sex for output areas across Scotland. This is the first time that such geographically detailed estimates of smoking have been made available.