Structural Conversions of Synthetic and Protein-Bound Iron-Sulfur Clusters.

Synthetic iron-sulfur clusters of general formulation [FemSqLl]z with core atoms Fe and S and terminal ligands L constitute a family of molecular clusters with remarkably diverse geometrical and electronic structures. Several structure types are also found in proteins. The large majority of research on these clusters has involved elucidation of physical properties. Here, we direct attention to reactivity in the form of cluster conversions in which the FemSq cores of reactants are transformed to new structures, usually of different nuclearity, in overall reactions such as self-assembly and fragment condensation and dissociation. An extensive body of core conversions, many of which have not been recognized as such, are presented including those in biological systems. All structural core types are depicted, and all core conversions are diagrammatically summarized. Clusters containing the cubane-type Fe4S4 core play a central role in conversion chemistry. The core conversion concept tends to reinforce the description of iron-sulfur cores as modular units subject to various covalent bond interactions that lead to different structures.

Atopic dermatitis and alcohol use - a meta-analysis and systematic review.

While several maternal exposures have been associated with an increased risk of atopic dermatitis (AD) in offspring, the effect of alcohol use during pregnancy on the risk of AD in offspring is unclear. Furthermore, it is unclear whether adults with AD have an increased alcohol use, although other poor health behaviours have been associated with AD including smoking and physical inactivity as well as psychiatric disease. In this systematic review and meta-analysis, the association between alcohol use and AD was investigated in two ways: 1) whether alcohol use (drinkers versus abstainers) during pregnancy is associated with AD in offspring and 2) whether AD is associated with increased alcohol use. The medical databases PubMed, EMBASE and Web of Science were searched, and data extraction was carried out by two independent reviewers. Eighteen studies were included in the qualitative analysis (comparing alcohol drinkers to abstainers), and 12 studies were included in the quantitative analysis. There was a positive association between alcohol use during pregnancy and development of AD in offspring (pooled odds ratio [OR] 1.16; 95% confidence interval [CI] 1.09-1.24). However, there was no consistent association between AD in adults and adolescents and alcohol use (pooled OR 1.06; 95% CI 0.92-1.23). There is a need for future well-designed prospective studies to firmly establish the association between alcohol use and AD.

Designing local solutions for emptying pit latrines in low-income urban settlements (Malawi).

A lack of effective options in local technology poses challenges when onsite household sanitation facilities are eventually filled to capacity in unplanned settlement areas within Mzuzu City, located in northern Malawi. Vacuum trucks currently dominate the market but focus on emptying septic tanks in the more easily accessible planned settlement areas, rather than servicing the pit latrines common in unplanned settlement areas. As a result, households in the unplanned settlement areas within Mzuzu rely primarily on manual pit emptying (i.e., shoveling by hand) or digging a new pit latrine. These practices have associated health risks and are limited by space constraints. This research focused on filling the technological gap through the design, development, and testing of a pedal powered modified Gulper pump using locally available materials and fabrication. A modified pedal powered Gulper technology was developed and demonstrated to be capable of lifting fecal sludge from a depth of 1.5 m with a mean flow rate of 0.00058 m3/s. If the trash content was low, a typical pit latrine with a volume of 1-4 m3 could be emptied within 1-2 h. Based on the findings in our research Phase IV, the pedal powered Gulper modification is promising as a potential emptying technology for lined pit latrines in unplanned settlement areas. The success rate of the technology is about 17% (5 out 30 sampled lined pit latrines were successful) and reflects the difficulty in finding a single technology that can work well in all types of pit latrines with varying contents. We note that cost should not be the only design criteria and acknowledge the challenge of handling trash in pit latrines.

Kinetics and mechanistic analysis of an extremely rapid carbon dioxide fixation reaction.

Carbon dioxide may react with free or metal-bound hydroxide to afford products containing bicarbonate or carbonate, often captured as ligands bridging two or three metal sites. We report the kinetics and probable mechanism of an extremely rapid fixation reaction mediated by a planar nickel complex [Ni(II)(NNN)(OH)](1-) containing a tridentate 2,6-pyridinedicarboxamidate pincer ligand and a terminal hydroxide ligand. The minimal generalized reaction is M-OH + CO(2) → M-OCO(2)H; with variant M, previous rate constants are ≲10(3) M(-1) s(-1) in aqueous solution. For the present bimolecular reaction, the (extrapolated) rate constant is 9.5 × 10(5) M(-1) s(-1) in N,N'-dimethylformamide at 298 K, a value within the range of k(cat)/K(M)≈10(5)-10(8) M(-1) s(-1) for carbonic anhydrase, the most efficient catalyst of CO(2) fixation reactions. The enthalpy profile of the fixation reaction was calculated by density functional theory. The initial event is the formation of a weak precursor complex between the Ni-OH group and CO(2), followed by insertion of a CO(2) oxygen atom into the Ni-OH bond to generate a four center Ni(η(2)-OCO(2)H) transition state similar to that at the zinc site in carbonic anhydrase. Thereafter, the Ni-OH bond detaches to afford the Ni(η(1)-OCO(2)H) fragment, after which the molecule passes through a second, lower energy transition state as the bicarbonate ligand rearranges to a conformation very similar to that in the crystalline product. Theoretical values of metric parameters and activation enthalpy are in good agreement with experimental values [ΔH(‡) = 3.2(5) kcal/mol].

Structural Analysis of Cubane-Type Iron Clusters.

The generalized cluster type [M4(µ3-Q)4L n ] x contains the cubane-type [M4Q4] z core unit that can approach, but typically deviates from, perfect Td symmetry. The geometric properties of this structure have been analyzed with reference to Td symmetry by a new protocol. Using coordinates of M and Q atoms, expressions have been derived for interatomic separations, bond angles, and volumes of tetrahedral core units (M4, Q4) and the total [M4Q4] core (as a tetracapped M4 tetrahedron). Values for structural parameters have been calculated from observed average values for a given cluster type. Comparison of calculated and observed values measures the extent of deviation of a given parameter from that required in an exact tetrahedral structure. The procedure has been applied to the structures of over 130 clusters containing [Fe4Q4] (Q = S2-, Se2-, Te2-, [NPR3]-, [NR]2-) units, of which synthetic and biological sulfide-bridged clusters constitute the largest subset. General structural features and trends in structural parameters are identified and summarized. An extensive database of structural properties (distances, angles, volumes) has been compiled in Supporting Information.

Selenium as a structural surrogate of sulfur: template-assisted assembly of five types of tungsten-iron-sulfur/selenium clusters and the structural fate of chalcogenide reactants.

Syntheses of five types of tungsten-iron-sulfur/selenium clusters, namely, incomplete cubanes, single cubanes, edge-bridged double cubanes (EBDCs), P(N)-type clusters, and double-cuboidal clusters, have been devised using the concept of template-assisted assembly. The template reactant is six-coordinate [(Tp*)W(VI)S(3)](1-) [Tp* = tris(3,5-dimethylpyrazolyl)hydroborate(1-)], which in the assembly systems organizes Fe(2+/3+) and sulfide/selenide into cuboidal [(Tp*)WFe(2)S(3)] or cubane [(Tp*)WFe(3)S(3)Q] (Q = S, Se) units. With appropriate terminal iron ligation, these units are capable of independent existence or may be transformed into higher-nuclearity species. Selenide is used as a surrogate for sulfide in cluster assembly in order to determine by X-ray structures the position occupied by an external chalcogenide nucleophile or an internal chalcogenide atom in the product clusters. Specific incorporation of selenide is demonstrated by the formation of [WFe(3)S(3)Se](2+/3+) cubane cores. Reductive dimerization of the cubane leads to the EBDC core [W(2)Fe(6)S(6)Se(2)](2+) containing µ(4)-Se sites. Reaction of these species with HSe(-) affords the P(N)-type cores [W(2)Fe(6)S(6)Se(3)](1+), in which selenide occupies µ(6)-Se and µ(2)-Se sites. The reaction of [(Tp*)WS(3)](1-), FeCl(2), and Na(2)Se yields the double-cuboidal [W(2)Fe(4)S(6)Se(3)](2+/0) core with µ(2)-Se and µ(4)-Se bridges. It is highly probable that in analogous sulfide-only assembly systems, external and internal sulfide reactants occupy corresponding positions in the cluster products. The results further demonstrate the viability of template-assisted cluster synthesis inasmuch as the reduced (Tp*)WS(3) unit is present in all of the clusters. Structures, zero-field Mössbauer data, and redox potentials are presented for each cluster type.

Synthesis of binucleating macrocycles and their nickel(II) hydroxo- and cyano-bridged complexes with divalent ions: anatomical variation of ligand features.

The planar NNN-pincer complexes [M(II)(pyN(2)(Me2))(OH)](1-) (M(II) = Ni, Cu) fix CO(2) in η(1)-OCO(2)H complexes; results for the copper system are described. Mn(II), Fe(II), Co(II), and Zn(II) behave differently, forming [M(II)(pyN(2)(Me2))(2)](2-) with N(4)O(2) coordination. Incorporation of the Ni(II) pincer into binucleating macrocycle 2 containing a triamino M(II) locus connected by two 1,3-biphenylene groups affords proximal Ni(II) and M(II) sites for investigation of the synthesis, structure, and reactivity of Ni-X-M bridge units. This ligand structure is taken as a reference for variations in M(II) atoms and binding sites and bridges X = OH(-) and CN(-) to produce additional members of the macrocyclic family with improved properties. Macrocycle 2 with a 22-membered ring is shown to bind M(II) = Mn, Fe, and Cu with hydroxo bridges. Introduction of the 4-Bu(i)O group (macrocycle 3) improves the solubility of neutral complexes such as those with Ni(II)-OH-Cu(II) and Ni(II)-CN-Fe(II) bridges. Syntheses of macrocycle 5 with a 7-Me-[12]aneSN(3) and macrocycle 6 with a 1,8-Me(2)-[14]aneN(4) M(II) binding site are described together with hydoxo-bridged Ni/Cu and cyano-bridged Ni/Fe complexes. This work was motivated by the presence of a Ni···(HO)-Fe bridge grouping in a reactive state of carbon monoxide dehydrogenase. Attempted decrease in Ni-(OH)-M distances (3.70-3.87 Å) to smaller values observed in the enzyme by use of macrocycle 4 having 1,2-biphenylene connectors led to a mononuclear octahedral Ni(II) complex. Bridge structural units are summarized, and the structures of 14 macrocyclic complexes including 8 with bridges are described.

Formation, spectroscopic characterization, and solution stability of an [Fe4S4]2+ cluster derived from ß-cyclodextrin dithiolate.

The formation and solution properties, including stability in mixed aqueous-Me(2)SO media, have been investigated for an [Fe(4)S(4)](2+) cluster derived from ß-cyclodextrin (CD) dithiolate. Clusters of the type [Fe(4)S(4)(SAr)(4)](2-) (Ar = Ph, C(6)H(4)-3-F) are generated in Me(2)SO by redox reactions of [Fe(4)S(4)(SEt)(4)](2-) with 2 equiv of ArSSAr. An analogous reaction with the intramolecular disulfide of 6(A),6(D)-(3-NHCOC(6)H(4)-1-SH)(2)-6(A),6(D)-dideoxy-ß-cyclodextrin (14), whose synthesis is described, affords a completely substituted cluster formulated as [Fe(4)S(4){ß-CD-(1,3-NHCOC(6)H(4)S)(2)}(2)](2-) (15). Ligand binding is indicated by a circular dichroism spectrum and also by UV-visible and isotropically shifted (1)H NMR spectra and redox behavior convincingly similar to [Fe(4)S(4)(SPh)(4)](2-). One formulation of 15 is a single cluster to which two dithiolates are bound, each in bidentate coordination. With there being no proven precedent for this binding mode, we show that the cluster [Fe(4)S(4)(S(2)-m-xyl)(2)](2-) is a single cubane whose m-xylyldithiolate ligands are bound in a bidentate arrangement. This same structure type was proposed for a cluster formulated as [Fe(4)S(4){ß-CD-(1,3-SC(6)H(4)S)(2)}(2)](2-) (16; Kuroda et al. J. Am. Chem. Soc.1988, 110, 4049-4050) and reported to be water-stable. Clusters 15 and 16 are derived from similar ligands differing only in the spacer group between the thiolate binding site and the CD platform. In our search for clusters stable in aqueous or organic-aqueous mixed solvents that are potential candidates for the reconstitution of scaffold proteins implicated in cluster biogenesis, 15 is the most stable cluster that we have thus far encountered under anaerobic conditions in the absence of added ligand.

Surveillance of RNase P, PMMoV, and CrAssphage in wastewater as indicators of human fecal concentration across urban sewer neighborhoods, Kentucky.

Wastewater surveillance has been widely used as a supplemental method to track the community infection levels of severe acute respiratory syndrome coronavirus 2. A gap exists in standardized reporting for fecal indicator concentrations, which can be used to calibrate the primary outcome concentrations from wastewater monitoring for use in epidemiological models. To address this, measurements of fecal indicator concentration among wastewater samples collected from sewers and treatment centers in four counties of Kentucky (N = 650) were examined. Results from the untransformed wastewater data over 4 months of sampling indicated that the fecal indicator concentration of human ribonuclease P (RNase P) ranged from 5.1 × 101 to 1.15 × 106 copies/ml, pepper mild mottle virus (PMMoV) ranged from 7.23 × 103 to 3.53 × 107 copies/ml, and cross-assembly phage (CrAssphage) ranged from 9.69 × 103 to 1.85 × 108 copies/ml. The results showed both regional and temporal variability. If fecal indicators are used as normalization factors, knowing the daily sewer system flow of the sample location may matter more than rainfall. RNase P, while it may be suitable as an internal amplification and sample adequacy control, has less utility than PMMoV and CrAssphage as a fecal indicator in wastewater samples when working at different sizes of catchment area. The choice of fecal indicator will impact the results of surveillance studies using this indicator to represent fecal load. Our results contribute broadly to an applicable standard normalization factor and assist in interpreting wastewater data in epidemiological modeling and monitoring.

The [MoFe3S4]2+ oxidation state: synthesis, substitution reactions, and structures of phosphine-ligated cubane-type clusters with the S=2 ground state.

The cluster [(Tp)MoFe(3)S(4)(PEt(3))(3)](1+) containing the cubane-type [MoFe(3)(µ(3)-S)(4)](2+) reduced core undergoes facile ligand substitution reactions at the iron sites leading to an extensive set of mono- and disubstituted species [(Tp)MoFe(3)S(4)(PEt(3))(3-n)L(n)](1-n) with L = halide, N(3)(-), PhS(-), PhSe(-), R(3)SiO(-), and R(3)SiS(-) and n = 1 and 2. Structures of 10 members of the set are reported. For two representative clusters, Curie behavior at 2-20 K indicates a spin-quintet ground state. Zero-field Mössbauer spectra consist of two doublets in a 2:1 intensity ratio. (57)Fe isomer shifts are consistent with the mean oxidation state Fe(3)(2.33+) arising from electron delocalization of the mixed-valence oxidation state description [Mo(3+)Fe(3+)Fe(2+)(2)]. Reaction of [(Tp)MoFe(3)S(4)(PEt(3))(2)Cl] with (Me(3)Si)(2)S affords [(Tp)MoFe(3)S(4)(PEt(3))(2)(SSiMe(3))], a likely first intermediate in the formation of the tricluster compound {[(Tp)MoFe(3)S(4)(PEt)(2)](3)S}(BPh(4)) from the reaction of [(Tp)MoFe(3)S(4)(PEt(3))(3)](BPh(4)) and NaSSiMe(3) in tetrahydrofuran (THF). The tricluster consists of three cluster units bound to a central µ(3)-S atom in a species of overall C(3) symmetry. Relatively few clusters in the [MoFe(3)S(4)](2+) oxidation state have been prepared compared to the abundance of clusters in the oxidized [MoFe(3)S(4)](3+) state. This work is the first comprehensive study of the [MoFe(3)S(4)](2+) state, one conspicuous feature of which is its ability to bind hard and soft σ-donors and strong to weak π-acid ligands. (Tp = tris(pyrazolyl)hydroborate(1-)).

Specific incorporation of chalcogenide bridge atoms in molybdenum/tungsten-iron-sulfur single cubane clusters.

An extensive series of heterometal-iron-sulfur single cubane-type clusters with core oxidation levels [MFe(3)S(3)Q](3+,2+) (M = Mo, W; Q = S, Se) has been prepared by means of a new method of cluster self-assembly. The procedure utilizes the assembly system [((t)Bu(3)tach)M(VI)S(3)]/FeCl(2)/Na(2)Q/NaSR in acetonitrile/THF and affords product clusters in 30-50% yield. The trisulfido precursor acts as a template, binding Fe(II) under reducing conditions and supplying the MS(3) unit of the product. The system leads to specific incorporation of a µ(3)-chalcogenide from an external source (Na(2)Q) and affords the products [((t)Bu(3)tach)MFe(3)S(3)QL(3)](0/1-) (L = Cl(-), RS(-)), among which are the first MFe(3)S(3)Se clusters prepared. Some 16 clusters have been prepared, 13 of which have been characterized by X-ray structure determinations including the incomplete cubane [((t)Bu(3)tach)MoFe(2)S(3)Cl(2)(µ(2)-SPh)], a possible trapped intermediate in the assembly process. Comparisons of structural and electronic features of clusters differing only in atom Q at one cubane vertex are provided. In comparative pairs of complexes differing only in Q, placement of one selenide atom in the core increases core volumes by about 2% over the Q = S case, sets the order Q = Se > S in Fe-Q bond lengths and Q = S > Se in Fe-Q-Fe bond angles, causes small positive shifts in redox potentials, and has an essentially nil effect on (57)Fe isomer shifts. Iron mean oxidation states and charge distributions are assigned to most clusters from isomer shifts. ((t)Bu(3)tach = 1,3,5-tert-butyl-1,3,5-triazacyclohexane).

Cubane-type Fe4S4 clusters with chiral thiolate ligation: formation by ligand substitution, detection of intermediates by 1H NMR, and solid state structures including spontaneous resolution upon crystallization.

Cubane-type clusters [Fe(4)S(4)(SR*)(4)](2-) containing chiral thiolate ligands with R* = CH(Me)Ph (1), CH(2)CH(Me)Et (2), and CH(2)CH(OH)CH(2)OH (3) have been prepared by ligand substitution in the reaction systems [Fe(4)S(4)(SEt)(4)]/R*SH (1-3, acetonitrile) and [Fe(4)S(4)Cl(4)](2-)/NaSR*(3, Me(2)SO). Reactions with successive equivalents of thiol or thiolate generate the species [Fe(4)S(4)L(4-n)(SR*)(n)](2-) (L = SEt, Cl) with n = 1-4. Clusters 1 and 2 were prepared with racemic thiols leading to the possible formation of one enantiomeric pair (n = 1) and seven diastereomers and their enantiomers (n = 2-4). Reactions were monitored by isotropically shifted (1)H NMR spectra in acetonitrile or Me(2)SO. In systems affording 1 and 2 as final products, individual mixed-ligand species could not be detected. However, crystallization of (Et(4)N)(2)[1] afforded 1-[SS(RS)(RS)] in which two sites are disordered because of occupancy of R and S ligands. Similarly, (Et(4)N)(2)[2] led to 2-[SSSS], a consequence of spontaneous resolution upon crystallization. The clusters 3-[RRRR] and 3-[SSSS] were obtained from enantiomerically pure thiols. Successive reactions lead to detection of species with n = 1-4 by appearance of four pairs of diastereotopic SCH(2) signals in both acetonitrile and Me(2)SO reaction systems. Identical spectra were obtained with racemic, R-(-), and S-(+) thiols, indicating that ligand-ligand interactions are too weak to allow detection of diastereomers (e.g., [SSSS] vs [SSRR]). The stability of 3 in Me(2)SO/H(2)O media is described.

Fast carbon dioxide fixation by 2,6-pyridinedicarboxamidato-nickel(II)-hydroxide complexes: influence of changes in reactive site environment on reaction rates.

The planar complexes [Ni(II)(pyN(2)(R2))(OH)](-), containing a terminal hydroxo group, are readily prepared from N,N'-(2,6-C(6)H(3)R(2))-2,6-pyridinedicarboxamidate(2-) tridentate pincer ligands (R(4)N)(OH), and Ni(OTf)(2). These complexes react cleanly and completely with carbon dioxide in DMF solution in a process of CO(2) fixation with formation of the bicarbonate product complexes [Ni(II)(pyN(2)(R2))(HCO(3))](-) having η(1)-OCO(2)H ligation. Fixation reactions follow second-order kinetics (rate = k(2)'[Ni(II)-OH][CO(2)]) with negative activation entropies (-17 to -28 eu). Reactions were monitored by growth and decay of metal-to-ligand charge-transfer (MLCT) bands at 350-450 nm. The rate order R = Me > macro > Et > Pr(i) > Bu(i) > Ph at 298 K (macro = macrocylic pincer ligand) reflects increasing steric hindrance at the reactive site. The inherent highly reactive nature of these complexes follows from k(2)' ≈ 10(6) M(-1) s(-1) for the R = Me system that is attenuated by only 100-fold in the R = Ph complex. A reaction mechanism is proposed based on computation of the enthalpic reaction profile for the R = Pr(i) system by DFT methods. The R = Et, Pr(i), and Bu(i) systems display biphasic kinetics in which the initial fast process is followed by a slower first order process currently of uncertain origin.

Wastewater Sample Site Selection to Estimate Geographically Resolved Community Prevalence of COVID-19: A Sampling Protocol Perspective.

Wastewater monitoring for virus infections within communities can complement conventional clinical surveillance. Currently, most SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) clinical testing is voluntary and inconsistently available, except for a few occupational and educational settings, and therefore likely underrepresents actual population prevalence. Randomized testing on a regular basis to estimate accurate population-level infection rates is prohibitively costly and is hampered by a range of limitations and barriers associated with participation in clinical research. In comparison, community-level fecal monitoring can be performed through wastewater surveillance to effectively surveil communities. However, epidemiologically defined protocols for wastewater sample site selection are lacking. Herein, we describe methods for developing a geographically resolved population-level wastewater sampling approach in Jefferson County, Kentucky, and present preliminary results. Utilizing this site selection protocol, samples (n = 237) were collected from 17 wastewater catchment areas, September 8 to October 30, 2020 from one to four times per week in each area and compared to concurrent clinical data aggregated to wastewater catchment areas and county level. SARS-CoV-2 RNA was consistently present in wastewater during the studied period, and varied by area. Data obtained using the site selection protocol showed variation in geographically resolved wastewater SARS-CoV-2 RNA concentration compared to clinical rates. These findings highlight the importance of neighborhood-equivalent spatial scales and provide a promising approach for viral epidemic surveillance, thus better guiding spatially targeted public health mitigation strategies.

Fasted and fed state human duodenal fluids: Characterization, drug solubility, and comparison to simulated fluids and with human bioavailability.

Accurate in vivo predictions of intestinal absorption of low solubility drugs require knowing their solubility in physiologically relevant dissolution media. Aspirated human intestinal fluids (HIF) are the gold standard, followed by simulated intestinal HIF in the fasted and fed state (FaSSIF/FeSSIF). However, current HIF characterization data vary, and there is also some controversy regarding the accuracy of FaSSIF and FeSSIF for predicting drug solubility in HIF. This study aimed at characterizing fasted and fed state duodenal HIF from 16 human volunteers with respect to pH, buffer capacity, osmolarity, surface tension, as well as protein, phospholipid, and bile salt content. The fasted and fed state HIF samples were further used to investigate the equilibrium solubility of 17 representative low-solubility small-molecule drugs, six of which were confidential industry compounds and 11 were known and characterized regarding chemical diversity. These solubility values were then compared to reported solubility values in fasted and fed state HIF, FaSSIF and FeSSIF, as well as with their human bioavailability for both states. The HIF compositions corresponded well to previously reported values and current FaSSIF and FeSSIF compositions. The drug solubility values in HIF (both fasted and fed states) were also well in line with reported solubility data for HIF, as well as simulated FaSSIF and FeSSIF. This indicates that the in vivo conditions in the proximal small intestine are well represented by simulated intestinal fluids in both composition and drug equilibrium solubility. However, increased drug solubility in the fed vs. fasted states in HIF did not correlate with the human bioavailability changes of the same drugs following oral administration in either state.

A rapid assessment of wastewater for genomic surveillance of SARS-CoV-2 variants at sewershed scale in Louisville, KY.

In this communication, we report on the genomic surveillance of SARS-CoV-2 using wastewater samples in Jefferson County, KY. In February 2021, we analyzed seven wastewater samples for SARS-CoV-2 genomic surveillance. Variants observed in smaller catchment areas, such as neighborhood manhole locations, were not necessarily consistent when compared to associated variant results in downstream treatment plants, suggesting catchment size or population could impact the ability to detect diversity.

Reactions of the terminal Ni(II)-OH group in substitution and electrophilic reactions with carbon dioxide and other substrates: structural definition of binding modes in an intramolecular Ni(II)...Fe(II) bridged site.

A singular feature of the catalytic C-cluster of carbon monoxide dehydrogenase is a sulfide-bridged Ni...Fe locus where substrate is bound and transformed in the reversible reaction CO + H(2)O right harpoon over left harpoon CO(2) + 2H(+) + 2e(-). A similar structure has been sought in this work. Mononuclear planar Ni(II) complexes [Ni(pyN(2)(Me2))L](1-) (pyN(2)(Me2) = bis(2,6-dimethylphenyl)-2,6-pyridinedicarboxamidate(2-)) derived from a NNN pincer ligand have been prepared including L = OH(-) (1) and CN(-) (7). Complex 1 reacts with ethyl formate and CO(2) to form unidentate L = HCO(2)(-) (5) and HCO(3)(-) (6) products. A binucleating macrocycle was prepared which specifically binds Ni(II) at a NNN pincer site and five-coordinate Fe(II) at a triamine site. The Ni(II) macrocyle forms hydroxo (14) and cyanide complexes (15) analogous to 1 and 7. Reaction of 14 with FeCl(2) alone and with ethyl formate and 15 with FeCl(2) affords molecules with the Ni(II)-L-Fe(II) bridge unit in which L = mu(2):eta(1)-OH(-) (17) and mu(2):eta(2)-HCO(2)(-) (18) and -CN(-) (19). All bridges are nonlinear (17, 140.0 degrees ; 18, M-O-C 135.9 degrees (Ni), 120.2 degrees (Fe); 19, Ni-C-N 170.3 degrees , Fe-N-C 141.8 degrees ) with Ni...Fe separations of 3.7-4.8 A. The Ni(II)Fe(II) complexes, lacking appropriate Ni-Fe-S cluster structures, are not site analogues, but their synthesis and reactivity provide the first demonstration that molecular Ni(II)...Fe(II) sites and bridges can be attained, a necessity in the biomimetic chemistry of C-clusters.

Stabilization of 3:1 site-differentiated cubane-type clusters in the [Fe(4)S(4)](1+) core oxidation state by tertiary phosphine ligation: synthesis, core structural diversity, and S = 1/2 ground states.

An extensive series of 3:1 site-differentiated cubane-type clusters [Fe(4)S(4)(PPr(i)(3))(3)L] (L = Cl(-), Br(-), I(-), RO(-), RS(-), RSe(-)) has been prepared in 40-80% yield by two methods: ligand substitution of [Fe(4)S(4)(PPr(i)(3))(4)](1+) in tetrahydrofuran (THF)/acetonitrile by reaction with monoanions, and reductive cleavage of ligand substrates (RSSR, RSeSeR, I(2)) by the all-ferrous clusters [Fe(8)S(8)(PPr(i)(3))(6)]/[Fe(16)S(16)(PPr(i)(3))(8)] in THF. These neutral clusters are stable and do not undergo ligand redistribution reactions involving charged species in benzene and THF solutions. X-ray structural studies confirm the cubane stereochemistry but with substantial and variable distortions of the [Fe(4)S(4)](1+) core from idealized cubic core geometry. Based on Fe-S bond lengths, seven clusters were found to have compressed tetragonal distortions (4 short and 8 long bonds), and the remaining seven display other types of distortions with different combinations of long, short, and intermediate bond lengths. These results further emphasize the facile deformabililty of this core oxidation state previously observed in [Fe(4)S(4)(SR)(4)](3-) clusters. The Fe(2.25+) mean oxidation state was demonstrated from (57)Fe isomer shifts, and the appearance of two quadrupole doublets arises from the spin-coupled |9/2,4,1/2> state. The S = 1/2 ground state was further supported by electron paramagnetic resonance spectra and magnetic susceptibility data.

Reactions of monodithiolene tungsten(VI) sulfido complexes with copper(I) in relation to the structure of the active site of carbon monoxide dehydrogenase.

Reactions directed at the synthesis of structural analogues of the active site of molybdenum-containing carbon monoxide dehydrogenase have been investigated utilizing [WO(2)S(bdt)](2-) (1) and [WOS(2)(bdt)](2-) (2) and sterically hindered [Cu(R)L] or [Cu(SSiR'(3))(2)](-) as reactants. All successful reactions of 2 afford the binuclear W(VI)/Cu(I) products [WO(bdt)(mu(2)-S)(2)Cu(L)](2-/-) with L = carbene (3), Ar*S (4), Ar* (7), SSiR(3) (R = Ph (5), Pr(i) (6)). Similarly, [W(bdt)(OSiPh(3))S(2)](-) leads to [W(bdt)(OSiPh(3))(mu(2)-S)(2)Cu(SAr*)](-) (8). These complexes, with apical oxo and basal dithiolato and sulfido coordination (excluding 8), terminal thiolate ligation at Cu(I) (4-6, 8), and W-(mu(2)-S)-Cu bridging, bear a structural resemblance to the enzyme site. Differences include two bridges instead of one and the absence of basal oxo/hydroxo ligation. Complex 8 differs from the others by utilizing apical and basal sulfido ligands in bridge formation. Related reaction systems based on 1 gave 4 in small yield or product mixtures in which the desired monobridged complex [WO(2)(bdt)(mu(2)-S)Cu(R)](2-) was not detected. Mass spectrometric analysis of the reaction system with L = carbene suggests that any monobridged species forms may converted to the dibridged form by disproportionation. In these experiments, the use of W(VI) preserves the structural integrity of Mo(VI), whose analogues of 1 and 2 have not been isolated. (Ar* = 2,6-bis(2,4,6-triisopropylphenyl)phenyl, bdt = benzene-1,2-dithiolate(2-)).