Aspherical-atom modeling of coordination compounds by single-crystal X-ray diffraction allows the correct metal atom to be identified.

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.

Triostin a derived cyclopeptide as architectural template for the alignment of four recognition units.

The DNA bisintercalator triostin A is structurally based on a disulfide-bridged depsipeptide scaffold that provides preorganization of two quinoxaline units in 10.5 Å distance. Triostin A analogues are synthesized with nucleobase recognition units replacing the quinoxalines and containing two additional recognition units in between. Thus, four nucleobase recognition units are organized on a rigid template, well suited for DNA double strand interactions. The new tetra-nucleobase binders are synthesized as aza-TANDEM derivatives lacking the N-methylation of triostin A and based on a cyclopeptide backbone. Synthesis of two tetra-nucleobase aza-TANDEM derivatives is established, DNA interaction analyzed by microscale thermophoresis, cytotoxic activity studied and a nucleobase sequence dependent self-aggregation investigated by mass spectrometry.

Crystalline guanine adducts of natural and synthetic trioxacarcins suggest a common biological mechanism and reveal a basis for the instability of trioxacarcin A.

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.

Selective synthesis and redox sequence of a heterobimetallic nickel/copper complex of the noninnocent Siamese-twin porphyrin.

The Siamese-twin porphyrin (1H4) is a redox noninnocent pyrazole-expanded porphyrin with two equivalent dibasic {N4} binding sites. It is now shown that its selective monometalation can be achieved to give the nickel(II) complex 1H2Ni with the second {N4} site devoid of a metal ion. This intermediate is then cleanly converted to 1Ni2 and to the first heterobimetallic Siamese-twin porphyrin 1CuNi. Structural characterization of 1H2Ni shows that it has the same helical structure previously seen for 1Cu2, 1Ni2, and free base 1H6(2+). Titration experiments suggest that the metal-devoid pocket of 1H2Ni can accommodate two additional protons, giving [1H4Ni](2+). Both bimetallic complexes 1Ni2 and 1CuNi feature rich redox chemistry, similar to the recently reported 1Cu2, 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 [1Ni2](+) and [1CuNi](+) as well as twice oxidized [1CuNi](2+), has been experimentally derived from comparison of the electrochemical properties of the complete series of complexes 1Cu2, 1Ni2, 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 [1Ni2](+) and [1CuNi](2+) cleanly converts them to metal-oxidized redox isomers with axial EPR spectra typical for Ni(III) having significant dz(2)(1) 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.

Structure solution of DNA-binding proteins and complexes with ARCIMBOLDO libraries.

Protein-DNA interactions play a major role in all aspects of genetic activity within an organism, such as transcription, packaging, rearrangement, replication and repair. The molecular detail of protein-DNA interactions can be best visualized through crystallography, and structures emphasizing insight into the principles of binding and base-sequence recognition are essential to understanding the subtleties of the underlying mechanisms. An increasing number of high-quality DNA-binding protein structure determinations have been witnessed despite the fact that the crystallographic particularities of nucleic acids tend to pose specific challenges to methods primarily developed for proteins. Crystallographic structure solution of protein-DNA complexes therefore remains a challenging area that is in need of optimized experimental and computational methods. The potential of the structure-solution program ARCIMBOLDO for the solution of protein-DNA complexes has therefore been assessed. The method is based on the combination of locating small, very accurate fragments using the program Phaser and density modification with the program SHELXE. Whereas for typical proteins main-chain α-helices provide the ideal, almost ubiquitous, small fragments to start searches, in the case of DNA complexes the binding motifs and DNA double helix constitute suitable search fragments. The aim of this work is to provide an effective library of search fragments as well as to determine the optimal ARCIMBOLDO strategy for the solution of this class of structures.

Structure of sulfamidase provides insight into the molecular pathology of mucopolysaccharidosis IIIA.

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 Å 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.

Selective functionalization of a bis-silylene.

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-iPr3C6H2) 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.

Siamese-twin porphyrin: a pyrazole-based expanded porphyrin of persistent helical conformation.

The 3+3-type synthesis of a pyrazole-based expanded porphyrin 22 H4, a hexaphyrin analogue named Siamese-twin porphyrin, and its homobimetallic diamagnetic nickel(II) and paramagnetic copper(II) complexes, 22 Ni2 and 22 Cu2, 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 22 H4. 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 {N4} 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 22 H6(2+), 22 Ni2, and 22 Cu2 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.

A super-reduced diferrous [2Fe-2S] cluster.

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. (57)Fe Mössbauer 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).

Donor-acceptor stabilized silaformyl chloride.

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·SiH(Cl)=O·B(C(6)F(5))(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 new dimension in cyclic coinage metal pyrazolates: decoration with a second ring of coinage metals supported by inter-ring metallophilic interactions.

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

Donor-acceptor-stabilized silicon analogue of an acid anhydride.

A stable silicon analogue of an acid anhydride {PhC(Bu(t)N)(2)}Si{═O·B(C(6)F(5))(3)}O-Si(H){═O·B(C(6)F(5))(3)}{(NBu(t))(HNBu(t))CPh} (4) with a O═Si-O-Si═O core has been prepared by treating monochlorosilylene PhC(Bu(t)N)(2)SiCl (1) with H(2)O·B(C(6)F(5))(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.

N-heterocyclic carbene stabilized dichlorosilylene transition-metal complexes of V(I), Co(I), and Fe(0).

Reactions of N-heterocyclic carbene stabilized dichlorosilylene IPr·SiCl(2) (1) (IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene) with (η(5)-C(5)H(5))V(CO)(4), (η(5)-C(5)H(5))Co(CO)(2), and Fe(2)(CO)(9) afford dichlorosilylene complexes IPr·SiCl(2)·V(CO)(3)(η(5)-C(5)H(5)) (2), IPr·SiCl(2)·Co(CO)(η(5)-C(5)H(5)) (3), and IPr·SiCl(2)·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 multinuclear ((1)H, (13)C, and (29)Si) NMR spectroscopy. Molecular structures of 2-4 have been determined by single crystal X-ray crystallographic studies and refined with nonspherical scattering factors.

Neutral pentacoordinate silicon fluorides derived from amidinate, guanidinate, and triazapentadienate ligands and base-induced disproportionation of Si2Cl6 to stable silylenes.

Pentacoordinate silicon fluorides L(1)SiF(3) (2a), L(2)SiF(3) (2b), and (L(3)SiF(2))(2) (2c)(2) based on amidinate (L(1) = PhC(N(t)Bu)(2)), guanidinate (L(2) = 1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a]pyrimidinate), and triazapentadienate (L(3) = NC(NMe(2))NC(NMe(2))NAr; Ar = 2,6-(i)Pr(2)C(6)H(3)) ligands were prepared by fluorination of the corresponding chlorosilanes L(1)SiCl(3) (1a), L(2)SiCl(3) (1b), and L(3)SiCl(2) (1c) with Me(3)SnF at ambient temperature. Compounds 1b, 1c, 2a, 2b, and (2c)(2) were characterized by (1)H, (13)C, (19)F, and (29)Si 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 L(3)SiF(2) (2c) is dimeric both in the solid state and in solution, whereas its chloro-analogue 1c is monomeric. The attempted synthesis of diamidinatotetrachlorodisilane by reaction of lithium amidinate with Si(2)Cl(6) led to the formation of the silane (1a) and the silylene L(1)SiCl (3). Reaction of Si(2)Cl(6) with N-heterocyclic carbenes (NHC) afforded NHC adducts of dichlorosilylene and SiCl(4). A one pot method for the preparation of base-stabilized silylenes from Si(2)Cl(6) is discussed.