Browsing by Author "Proepper, Kevin"

When pyrazolate ligands with thioether chelate arms are used in cyclic coinage metal pyrazolates [Au(mu-pz)]IV, the inner gold ring can be framed with an outer silver ring to give novel heterometallic double-crowned complexes [AuAg(mu-L-x) (BF4)](4). They feature short intramolecular in-plane Ag-Au interactions, are stable as octanuclear species in solution, and show promising luminescence properties.

A biomimetic [2Fe-2S] cluster has been isolated in the fully reduced diferrous form and characterized by X-ray diffraction. This completes a consistent series of synthetic analogues of protein-bound [2Fe-2S](z) redox centers (z = 2+, 1+, 0) with identical capping ligands. Fe-57 Mossbauer data of the extremely oxidation-sensitive complex compare well with those of the very few reports of all-ferrous ferredoxins and Rieske centers; they confirm the S-T = 0 ground state and establish a lower limit for the exchange coupling, -J >= 30 cm(-1).

Single-crystal X-ray diffraction (XRD) is often considered the gold standard in analytical chemistry, as it allows element identification as well as determination of atom connectivity and the solid-state structure of completely unknown samples. Element assignment is based on the number of electrons of an atom, so that a distinction of neighboring heavier elements in the periodic table by XRD is often difficult. A computationally efficient procedure for aspherical-atom least-squares refinement of conventional diffraction data of organometallic compounds is proposed. The iterative procedure is conceptually similar to Hirshfeld-atom refinement (Acta Crystallogr. Sect. A 2008, 64, 383-393; IUCrJ. 2014, 1,61-79), but it relies on tabulated invariom scattering factors (Acta Crystallogr. Sect. B 2013, 69, 91-104) and the Hansen/Coppens multipole model; disordered structures can be handled as well. Five linear-coordinate 3d metal complexes, for which the wrong element is found if standard independent-atom model scattering factors are relied upon, are studied, and it is shown that only aspherical-atom scattering factors allow a reliable assignment. The influence of anomalous dispersion in identifying the correct element is investigated and discussed.

X-ray crystallographic characterization of products derived from natural and fully synthetic trioxacarcins, molecules with potent antiproliferative effects, illuminates aspects of their reactivity and mechanism of action. Incubation of the fully synthetic trioxacarcin analog 3, which lacks one of the carbohydrate residues present in the natural product trioxacarcin A (1) as well as oxygenation at C2 and C4 yet retains potent antiproliferative effects, with the self-complimentary duplex oligonucleotide d(AACCGGTT) led to production of a crystalline covalent guanine adduct (6). Adduct 6 is closely analogous to gutingimycin (2), the previously reported guanine adduct derived from incubation of natural trioxacarcin A (1) with duplex DNA, suggesting that 3 and 1 likely share a common basis of cytotoxicity. In addition, we isolated a novel, dark-red crystalline guanine adduct (7) from incubation of trioxacarcin A itself with the self-complimentary duplex oligonucleotide d(CGTATACG). Crystallographic analysis suggests that 7 is an anthraquinone derivative, which we propose arises by a sequence of guanosine alkylation within duplex DNA, depurination, base-catalyzed elimination of the trioxacarcinose A carbohydrate residue, and oxidative rearrangement to form an anthraquinone. We believe that this heretofore unrecognized chemical instability of natural trioxacarcins may explain why trioxacarcin analogs lacking C4 oxygenation exhibit superior chemical stabilities yet, as evidenced by structure 3, retain a capacity to form lesions with duplex DNA. (C) 2014 Elsevier Ltd. All rights reserved.

Formyl chloride (H(Cl)C=O) is unstable at room temperature and decomposes to HCl and CO. Silicon analogue of formyl chloride, silaformyl chloride IPr center dot SiH(Cl)=O center dot B(C6F5)(3) (3) (IPr = 1,3-bis(2,6-diisopropyl-phenyl)imidazol-2-ylidene), was stabilized by Lewis donor-acceptor ligands. Compound 3 is not only the first stable acyclic silacarbonyl compound but also the first silacarbonyl halide reported so far.

A stable silicon analogue of an acid anhydride {PhC((BuN)-N-t)(2)}Si{=O center dot B(C6F5)(3)}O-Si(H){=O center dot B(C6F5)(3)}{(NBut)(HNBut)CPh} (4) with a O=Si-O-Si=O core has been prepared by treating monochlorosilylene PhC((BuN)-N-t)(2)SiCl (1) with H2O center dot B(C6F5)(3) in the presence of NHC (NHC = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene). Compound 4 has been characterized by elemental analysis and multinuclear NMR spectroscopic investigations. The molecular structure of 4 has been established by single-crystal X-ray diffraction studies, and DFT calculations support the experimental results.

The scarcely known chemistry of silver(I) halides with a series of heterocyclic thiones in acetonitrile (or methanol-acetonitrile) is described. Silver(I) chloride with a series of imidazolidine-2-thiones [C3H5NS(N-R)] in the presence of one equivalent of PPh3 with respect to the thione ligand has yielded chloro-bridged dinuclear complexes, [Ag-2(mu-Cl)(2)(kappa(1)-S-C3H5NS(N-R))(2)(PPh3)(2)] (1, R = H; 2, R = Me; 3, R = Et), and in the presence of two equivalents of PPh3, it has yielded mononuclear complexes, [Ag(kappa(1)-Cl)(kappa(1)-S-C3H5NS(N-R))(PPh3)(2)] (4, R = Me; 5, R = Et). The n-propyl-imidazolidine-2-thione with silver(I) chloride formed only a mononuclear complex, [Ag(kappa(1)-Cl)(kappa(1)-S-C3H5NS(N-Pr-n))(PPh3)(2)] (6), in the presence of one or two equivalents of PPh3. In contrast, silver(I) bromide with C3H5NS(N-R) in the presence of one or two equivalents of PPh3 with respect to the thione ligand has yielded bromide-bridged dinuclear complexes, [Ag-2(mu-Br)(2)(kappa(1)-S-C3H5NS(N-R))(2)(PPh3)(2)] (7, R = Me; 8, R = Et; 9, R = Pr-n). The related thio-ligands, namely, 1-methyl-imidazoline-2-thione and thiazolidine-2-thione with silver(I) bromide in the presence of one or two equivalents of PPh3 have formed bromide bridged dimeric [Ag-2(mu-Br)(2)(kappa(1)-S-C3H3NS(N-Me))(2)(PPh3)(2)] (10) or mononuclear Ag(kappa(1)-Br)(kappa(1)-S-C3H5NS2)(PPh3)(2)] (11) complexes respectively. The 2,4-dithiouracil (C4H4N2S2) with silver(I) chloride/bromide and PPh3 has yielded hetero-bridged dinuclear complexes, [Ag-2(mu-S,S-C4H3N2S2)(mu-X)(PPh3)(4)] (X = Cl, 12; Br, 13) involving rupture of Ag-X bonds directly with a thio-ligand, a rare case of such rupture in metal-heterocyclic thione chemistry. (C) 2013 Elsevier B. V. All rights reserved.

The structure of ceftazidime pentahydrate, a third generation cephalosporin antibiotic, is reported. Data collection was carried out in a remarkably short time with synchrotron radiation and the latest detector technology, illustrating that single-crystal X-ray diffraction can be used as a technique for screening hundreds of compounds in a short amount of time. Structure refinement made use of invarioms, namely non-spherical scattering factors, which allow more information to be derived from a diffraction experiment. Properties that can be screened are bond-topological parameters, empirical hydrogen-bond energies, molecular dipole moments and electrostatic potentials.

A new monoclinic solvate containing two molecules of the thiopeptide antibiotic thiostrepton in the asymmetric unit has been crystallized in space group P2(1). Single-crystal diffraction data to a resolution of 0.64 angstrom were collected at the SLS synchrotron, allowing structure solution by direct methods and resolution of the disorder present. Valence electron density can be observed in the Fourier residual density from refinement with the independent-atom model, which is a prerequisite for successful application of more sophisticated aspherical-atom scattering factors such as the invariom model when aiming to improve the structural model. Invariom refinement improves quality indicators such as R-1(F) for thiostrepton, as previously demonstrated for small molecules. The nonspherical electron-density model also allows the direct derivation of a dipole moment and an electrostatic potential for the whole molecule, which is discussed in the context of antibiotic activity and molecular recognition.

Reactions of N-heterocyclic carbene stabilized dichlorosilylene IPr center dot SiCl2 (1) (IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene) with (eta(5)-C5H5)V(CO)(4), (eta(5)-C5H5)Co(CO)(2), and Fe-2(CO)(9) afford dichlorosilylene complexes IPr center dot SiCl2 center dot V(CO)(3)(eta(5)-C5H5) (2), IPr center dot SiCl2 center dot Co(CO)-(eta(5)-C5H5) (3), and IPr center dot SiCl2 center dot Fe(CO)(4) (4), respectively. Complexes 2-4 are stable under an inert atmosphere, are soluble in common organic solvents, and have been characterized by elemental analysis and multinudear (H-1, C-13, and Si-29) NMR spectroscopy. Molecular structures of 2-4 have been determined by single crystal X-ray crystallographic studies and refined with nonspherical scattering factors.

Pentacoordinate silicon fluorides (LSiF3)-Si-1 (2a), (LSiF3)-Si-2 (2b), and ((LSiF2)-Si-3)(2) (2c)(2) based on amidinate (L-1 = PhC((NBu)-Bu-t)(2)), guanidinate (L-2 = 1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a]pyrimidinate), and triazapentadienate = (L-3 = NC(NMe2)NC-(NMe2)NAr, Ar = 2,6-(Pr2C6H3)-Pr-i) ligands were prepared by fluorination of the corresponding chlorosilanes (LSiCl3)-Si-1 (1a), (LSiCl3)-Si-2 (1b), and (LSiCl2)-Si-3 (1c) with Me3SnF at ambient temperature. Compounds 1b. 1c, 2a, 2b, and (2c)(2) were characterized by H-1, C-13, F-19, and Si-29 NMR spectroscopic studies. Molecular structures of 1b, 1c, 2a, and (2c)(2) were determined by single crystal X-ray structural analysis. Invariom refinement involving non-spherical scattering factors of the Hansen-Coppens multipole model was performed for 1b. Compound (LSiF2)-Si-3 (2c) is dimeric both in the solid state and in solution, whereas its chloro-analogue lc is monomeric. The attempted synthesis of diamidinatotetrachlorodisilane by reaction of lithium amidinate with Si2Cl6 led to the formation of the silane (1a) and the silylene (LSiCl)-Si-1 (3). Reaction of Si2Cl6 with N-heterocyclic carbenes (NHC) afforded NHC adducts of dichlorosilylene and SiCl4. A one pot method for the preparation of base-stabilized silylenes from Si2Cl6 is discussed.

The reaction of LSiX (L = PhC(NtBu)(2), X = NPh2 (1), NMe2 (2)) with trimethylsilyl azide (3) resulted in silaimines [LSi(=NSiMe3)X] (X = NPh2 (5), NMe2 (7)). Similarly the reaction of 1 and 2 with adamantyl azide (4) yielded [LSi(=-NAd)X] (X = NPh2 (6), NMe2 (8), Ad = adamantyl) compounds. Silaimines 5-8 contain tetracoordinate silicon atoms. Compounds 6 and 8 are the first tetracoordinate silicon compounds having the terminal Si=NAd unit. All compounds were characterized by spectroscopic and spectrometric techniques. The molecular structures of 5, 6, and 8 were unequivocally established by single-crystal X-ray structure analysis.

Reaction of heteroleptic silylenes LSD( (L = PhC(NtBu)(2); X = PPh2 (1), NPh2 (2), NMe2 (3), OtBu (4)) with N2O resulted in the oxidized dimeric product [LSi(X)(mu-O)](2) (X = PPh2 (5), NPh2 (6), NMe2 (7), OtBu (8)), which contains a four -membered Si2O2 ring. Compounds 5-8 were characterized by spectroscopic and spectrometric techniques. The molecular structures of 5-8 were established by single-crystal X-ray structure analysis.

Functionalization of N-heterocyclic carbenes (NHCs) has an important influence on their stability, Lewis donor, and acceptor properties. In this study, we report on the selective functionalization of a four-membered N-heterocyclic bis-silylene (2,6-Ar2C6H3NSi:)(2) (1) (Ar = 2,4,6-iPr(3)C(6)H(2)) with mono-oxygen sources N2O and Me3NO. Treatment of 1 with N2O results in the selective formation of mono-silylene (2,6-Ar2C6H3NSi(OH)(2))(2,6-Ar2C6H3NSi:) (2) as a major product, along with a small amount of further oxidized product (2,6-Ar2C6H3NSi(OH)(2))(2) (3). Compound 2 is the first four-membered mono-silylene with a di-coordinate silicon atom.

The Siamese-twin porphyrin (1H(4)) is a redox noninnocent pyrazole-expanded porphyrin with two equivalent dibasic {N-4} binding sites. It is now shown that its selective monometalation can be achieved to give the nickel(II) complex 1H(2)Ni with the second {N-4} site devoid of a metal ion. This intermediate is then cleanly converted to 1Ni(2) and to the first heterobimetallic Siamese-twin porphyrin 1CuNi. Structural characterization of 1H(2)Ni shows that it has the same helical structure previously seen for 1Cu(2), 1Ni(2), and free base 1H(6)(2+). Titration experiments suggest that the metal-devoid pocket of 1H(2)Ni can accommodate two additional protons, giving [1H(4)Ni](2+). Both bimetallic complexes 1Ni(2) and 1CuNi feature rich redox chemistry, similar to the recently reported 1Cu(2), including two chemically reversible oxidations at moderate potentials between -0.3 and +0.5 V (vs Cp2Fe/Cp2Fe+). The locus of these oxidations, in singly oxidized [1Ni(2)](+) and [1CuNi](2+) as well as twice oxidized [1CuNi](2+), has been experimentally derived from comparison of the electrochemical properties of the complete series of complexes 1Cu(2), 1Ni(2), and 1CuNi, and from electron paramagnetic resonance (EPR) spectroscopy and X-ray absorption spectroscopy (XAS) (Ni and Cu K edges). All redox events are largely ligand-based, and in heterobimetallic 1CuNi, the first oxidation takes place within its Cu-subunit, while the second oxidation then occurs in its Ni-subunit. Adding pyridine to solutions of [1Ni(2)](+) and [1CuNi](2+) cleanly converts them to metal-oxidized redox isomers with axial EPR spectra typical for Nil having significant d(z)(21) character, reflecting close similarity with nickel complexes of common porphyrins. The possibility of selectively synthesizing heterobimetallic complexes 1MNi from a symmetric binucleating ligand scaffold, with the unusual situation of three distinct contiguous redox sites (M, Ni, and the porphyrin-like ligand), further expands the Siamese-twin porphyrin's potential to serve as an adjustable platform for multielectron redox processes in chemical catalysis and in electronic applications.

The 3+3-type synthesis of a pyrazole-based expanded porphyrin 22H(4), a hexaphyrin analogue named Siamese-twin porphyrin, and its homobimetallic diamagnetic nickel(II) and paramagnetic copper(II) complexes, 22Ni(2) and 22Cu(2), are described. The structure of the macrocycle composed of four pyrroles and two pyrazoles all linked by single carbon atoms, can be interpreted as two conjoined porphyrin-like subunits, with the two opposing pyrazoles acting as the fusion points. Variable-temperature 1D and 2D NMR spectroscopic analyses suggested a conformationally flexible structure for 22H(4). NMR and UV/Vis spectroscopic evidence as well as structural parameters proved the macrocycle to be non-aromatic, though each half of the molecule is fully conjugated. UV/Vis and NMR spectroscopic titrations of the free base macrocycle with acid showed it to be dibasic. In the complexes, each metal ion is coordinated in a square-planar fashion by a dianionic, porphyrin-like {N-4} binding pocket. The solid-state structures of the dication and both metal complexes were elucidated by single-crystal diffractometry. The conformations of the three structures are all similar to each other and strongly twisted, rendering the molecules chiral. The persistent helical twist in the protonated form of the free base and in both metal complexes permitted resolution of these enantiomeric helimers by HPLC on a chiral phase. The absolute stereostructures of 22H(6)(2+), 22Ni(2), and 22Cu(2) were assigned by a combination of experimental electronic circular dichroism (ECD) investigations and quantum-chemical ECD calculations. The synthesis of the first member of this long-sought class of expanded porphyrin-like macrocycles lays the foundation for the study of the interactions of the metal centers within their bimetallic complexes.

Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome), a fatal childhood-onset neurodegenerative disease with mild facial, visceral and skeletal abnormalities, is caused by an inherited deficiency of the enzyme N-sulfoglucosamine sulfohydrolase (SGSH; sulfamidase). More than 100 mutations in the SGSH gene have been found to reduce or eliminate its enzymatic activity. However, the molecular understanding of the effect of these mutations has been confined by a lack of structural data for this enzyme. Here, the crystal structure of glycosylated SGSH is presented at 2 A resolution. Despite the low sequence identity between this unique N-sulfatase and the group of O-sulfatases, they share a similar overall fold and active-site architecture, including a catalytic formylglycine, a divalent metal-binding site and a sulfate-binding site. However, a highly conserved lysine in O-sulfatases is replaced in SGSH by an arginine (Arg282) that is positioned to bind the N-linked sulfate substrate. The structure also provides insight into the diverse effects of pathogenic mutations on SGSH function in mucopolysaccharidosis type IIIA and convincing evidence for the molecular consequences of many missense mutations. Further, the molecular characterization of SGSH mutations will lay the groundwork for the development of structure-based drug design for this devastating neurodegenerative disorder.