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The racemic total synthesis of nitrabirine (5) together with its previously undescribed epimer 2-epi nitrabirine (5') is accomplished via a six-step route based on a biomimetic late-stage heterocyclization. This allowed the assignment of the relative configuration of nitrabirine by the lanthanide-induced shifts (LIS) experiment, which was later on confirmed by X-ray diffraction of obtained single crystals. Furthermore, oxidation studies demonstrated that the direct N-oxidation of nitrabirine does not yield nitrabirine N-oxide as reported earlier. In contrast, the reaction of hydrogen peroxide with nitrabirine (5) yields the salt 24', whereas 2-epi nitrabirine (5') surprisingly leads to a previously uncharacterized product 22 under the same conditions. Finally, a Fischer indole reaction gave access to novel tetracyclic nitrabirine derivatives 26a-d. A comprehensive biological evaluation of nitrabirine (5), 2-epi nitrabirine (5'), and all derivatives synthesized in this study revealed general biofilm dispersal effects against Candida albicans. Moreover, specific compounds showed moderate antibacterial activities as well as potent cytotoxic activities.

Three anthracene-based cyclophanes were synthesized and their binding properties towards nucleoside triphosphates were studied. A new polycyclic amine derived from dearomatized anthracene was identified as a major side product in the cyclization reaction between 9,10-anthracenedicarboxaldehyde and diethylenetriamine. Its structure was determined by single-crystal X-ray analysis. The cyclophanes were found to form 1:1 complexes with all nucleoside triphosphates as well as with pyrophosphate in a buffered aqueous solution at pH 6.2. A turn-on fluorescence response was observed for all nucleotides except for GTP, which demonstrated strong fluorescence quenching. The strongest turn-on fluorescence was observed for the largest receptor 3 in the presence of thymidine triphosphate (TTP). Based on the NMR and fluorescence experiments, two major binding modes for nucleotide complexes were identified.

Three cadmium(II) complexes of 1,3-diazinane-2-thione (diaz); dichloridotetrakis(1,3-diazinane-2-thione)cadmium(II), [Cd(diaz)4Cl2] (1), bis(thiocyanato-κN)bis(1,3-diazinane-2-thione)cadmium(II), [Cd(diaz)2(NCS)2] (2) and poly[diazidobis(1,3-diazinane-2-thione)cadmium(II)], [Cd(diaz)2(N3)2]n (3) were prepared and their crystal structures were determined by X-ray crystallography. The compounds 1 and 2 exist in the monomeric forms as discrete nonionic molecules. In 1, the cadmium atom is octahedrally coordinated by two trans chloride ions and four diaz ligands, while in 2, it is bound to two thione molecules and two thiocyanato ions through nitrogen atoms in a tetrahedral environment. The structure of 1 is stabilized by intramolecular N H⋯Cl hydrogen bonds and layers are formed by additional intermolecular N H⋯S hydrogen bonds. The crystal structure of 2 is characterized by intermolecular N H⋯S hydrogen bonding and S⋯S interactions. The complex 3 exists in the form of a polymeric chain consisting of [Cd(diaz)2(N3)2] units. In 3 each cadmium atom is octahedrally coordinated by two trans diaz ligands and four doubly-bridging, µ(1,3) azide groups. The coordination chain is stabilized by additional N H⋯N intrachain hydrogen bonds and, overall a 3D network is formed by interchain N H⋯N and N H⋯S hydrogen bonds. The complexes 1–3 were also characterized by IR and NMR spectroscopy, and the spectroscopic data indicated the coordination of ligands to cadmium(II).

The synthesis and characterization of four ferrocenyl thiocarboxylate complexes are reported. Thus, treatment of [Fe(η5-C5H5)(η5-C5H4S−)] (1) with one equivalent of the acid chlorides 2-ClC(O)-cC4H3X(2a, X = O; 2b, X = NMe) gave [Fe(η5-C5H5)(η5-C5H4SC(O)-2-cC4H3X)] (3a, X = O; 3b, X = NMe (b)). When 1,1′-[Fe(η5-C5H4S−)2] (4) was reacted with 2-ClC(O)-cC4H3X in a 1:2 molar ratio then the respective ferrocenyl-1,1'-bis(thiocarboxylates) 1,1′-[Fe(η5-C5H4SC(O)-2-cC4H3X)2] (5a, X = O; 5b, X = NMe (b)) were produced. The solid state structures of 5a and 5b were determined by X-ray crystal structure analysis. The Crystal structure of 5a indicated the presence of oxygen…oxygen contacts, the inter-oxygen distance is 0.13 A less than the sum of van der Waals radii. Investigation of Cambridge Structural Data base for 2-substtiuted furan molecules indicated the presence of short O…O contacts in 49 examples. Geometrical analysis of the O…O contacts indicated that the geometrical arrangement of these contacts is very similar to the well-defined C-X…X-C contacts (X = Cl, Br or I). Cyclic voltammetric studies of 3a, b and 5a, b showed reversible events at 158 and 243 mV for 3a, b and at 187 and 284 mV for 5a, b, using [NnBu4][B(C6F5)4] as the supporting electrolyte. It was found that the furyl-functionalized systems resulted in a significant higher Fc/Fc+ redox potential (E0′) as observed for the more electron-rich pyrrolyl derivatives. The Fc/Fc+ redox potential (E0′) for 5a, b is significantly higher than the one for 3a, b, due to the presence of two electron withdrawing thioester groups attached to the ferrocene in 5a, b.

The reaction of FcCH2OH with chlorophosphates gave ferrocenyl phosphates FcCH2OP(O)(OR)2 (Fc = Fe(η5-C5H5)(η4-C5H4)), which readily separate into phosphate anions and ferrocenyl carbo-cations. The latter species undergoes consecutive reactions, e. g. electrophilic aromatic substitutions. When nitriles, instead of alcohols, are treated with FcLi or tBuLi and chlorophosphates, chiral-pool based ferrocenyl imino phosphoramidates Fc-CR=N-P(O)(OR*)2 are formed, which are promising candidates for anionic homo phospho-Fries rearrangements. Moreover, the sterically demanding chiral chlorophosphate with R* enabled oxidative couplings of the imines to form a diferrocenyl azine. Similarly, the reaction of Fc-Li with 9-anthrylnitrile produced a 10-ferrocenyl-substituted product, contrary to a reaction at the C≡N functionality. A planar-chiral ortho-P(S)Ph2-functionalized ferrocenylmethanol also gave carbo-cations under acidic conditions. These species can be sulfurized in a unique way giving thio ethers, whereby the in situ formed 1,2-P(S)Ph2,CH2+ ferrocene cation acts as the sulfur and electron source. However, lowering the substrate concentration prevents sulfur migration, resulting in electrophilic substitution reactions with aromatic solvents. Planar-chiral ferrocenylmethyl thio or anisyl derivatives were applied as ligands in Pd-catalyzed Suzuki-Miyaura C,C cross-coupling for the atropselective synthesis of hindered biaryls with up to 26 % ee at low catalyst loadings (1 mol-% Pd).

The built-in o- and p-QM (QM = quinone methide) moieties in benzo[cd]azulen-3-ones account for an easy switch between the bridged 10π- and 6π-aromatic systems in organic synthesis. We report conjugate additions, oxidative nucleophilic substitutions of hydrogen, and reversible Michael additions under very mild conditions. In the presence of thiol nucleophiles, the protonated σH-adducts could be isolated and characterized. The typical preference for either the o- or p-QM moiety led to high regioselectivity. Furthermore, the inhibitory potency of the novel benzo[cd]azulenes against the human Pim-1 kinase was evaluated.

The temperature-dependent behavior within anionic phospho-Fries rearrangements (apFr) of P(O)(OFc)n(EAr)3–n (Fc = Fe(η5-C5H5)(η5-C5H4); E = O; Ar = phenyl, naphthyls, (R)-BINOL, [3]ferrocenophanyl; E = N, 1H-pyrrolyl, 1H-indolyl, 9H-carbazolyl; n = 1–3) is reported. While Fc undergoes one, the Ph-based apFr depends on temperature. First, the aryls are lithiated and rearranged, followed by Fc and N-heterocycles. Addition of Me2SO4 thus gave methylated Fc, contrary to non-organometallic aromatics giving mixtures of HO and MeO derivatives. The (R)-BINOL Fc phosphate gave Fc-rearranged phosphonate in 91% de. Exchanging O- with N-aliphatics prevented apFr, due to higher electron density at P. Also 1,2-N→C migrations were observed. X-ray analysis confirms 1D H bridge bonds for OH and NH derivatives. The differences in reactivity between N-aliphatic and N-aromatic phosphoramidates were verified by electrochemistry. The redox potentials revealed lower values for the electron-rich aliphatics, showing no apFr, prev...

Four ruthenium complexes of N’NS donor thiomethyl-azoimine ligands (L) of the general type trans -[Ru II (bipy)(L)(Cl) 2 ]( C1 – C4 ) (L = XC 6 H 4 N NC(COMe) NC 6 H 4 (2-SMe), X = H (L1), C1 ; CH 3 (L2), C2 ; Br (L3), C3 ; NO 2 (L4), C4 ) have been synthesized by the reaction of ruthenium trichloride trihydrate with the corresponding L ligands and bipyridine (bipy) in refluxing ethanol. The molecular structure of trans -[Ru(bpy)(L3)(Cl) 2 ]( C3 ) in the solid state is reported. The thiomethyl-azoimine ligands (L) bind as NN′ bidentate ligands with no direct Ru–S interaction. Furthermore, the complexes have been characterized by spectroscopic data (IR, UV/Vis and 1 H NMR) and cyclic voltammetry. The electrochemical parameters ( E L ( L )) of the azoimine ligands (L1–L4) are reported. The electronic excitations of a representative complex ( C3 ) are interpreted by DFT and TDDFT calculations.

New diorganobismuth(III) bromides of type [RN(CH2C6H4)2]BiBr [R = C6H5CH2 (1), C6H5CH2CH2 (2), and CH3OCH2CH2 (3)], based on the heterocyclic butterfly-like tetrahydro-dibenzo[c,f][1,5]azabismocine framework, were prepared starting from the corresponding RN(CH2C6H4Br-2)2 in a succession of reactions including ortho-lithiation and treatment of the dilithio derivative with BiBr3 in a 1 : 1 molar ratio. Further exchange reactions between bromides and appropriate metal halides or ammonium fluoride resulted in the formation of [RN(CH2C6H4)2]BiX [X = Cl and I for R = C6H5CH2 (4 and 5) and C6H5CH2CH2 (6 and 7) and X = F (8), Cl (9), and I (10) for R = CH3OCH2CH2]. All ten compounds were structurally characterized in solution by NMR and in the solid state by single-crystal X-ray diffraction. Strong transannular N→Bi interactions were observed in all the investigated diorganobismuth(III) halides, thus giving rise to hypervalent 10–Bi–4 species in 1, 2, 4–7 and 12–Bi–5 species in 3, 8–10, where the oxygen atom in the pendant arm is intramolecularly coordinated to bismuth. The molecules are associated in dimeric units by strong Bi⋯π arene interactions in 3, 4, and 10 (approx. 3.50 A) and by Bi⋯X interactions in 1, 5, and 7. Bromide 1, chloride 4, and iodide 5 are isostructural, but stronger polarization of the Bi–Cl bond favors Bi⋯π arene interaction in 4 over Bi⋯halide interactions, as observed in 1 and 5. In the isostructural series [RN(CH2C6H4)2]BiX (R = CH3OCH2CH2), Bi⋯oxygen interactions compensate the electron deficiency at bismuth in fluoride 8 and chloride 9, whereas the coordination sphere of bismuth is completed by a combination of Bi⋯π arene and Bi⋯halide interactions in bromide 3 and only by Bi⋯π arene interactions in iodide 10. Moreover, weak H⋯π arene and H⋯X intermolecular interactions, mainly of dispersion type, contribute to supramolecular networks in all three series of compounds.

The alkoxide Bi[OCMe2(2-C4H3S)]3 (1) is formed by the reaction of three equiv. of the alcohol HOCMe2(2-C4H3S) with Bi(OtBu)3 and subsequent hydrolysis provides the bismuth oxido cluster [Bi4O2{OCMe2(2-C4H3S)}8] (2). In contrast, the reaction of Bi(OtBu)3 and Bi[N(SiMe3)2]3 with the silanols HOSiMe2(2-C4H3X) (X = O, S, Se, and NMe), HOSiMe2(2-C4H2S-5-SiMe3) and HOSiMe2(3-C4H3S) leads to the formation of tris(heteroaryl)bismuthines Bi(2-C4H2X-5-R)3 [where X = O, R = H (3); X = S, R = H (4); X = S, R = SiMe3 (5); X = NMe, R = H (6); X = Se, R = H (7)] and Bi(3-C4H3S)3 (8). For the silanols, bismuth-carbon bond formation is observed rather than silanol-alcoholate or silanol-amide exchange. The structures of compounds 1, 2, and 4-7a in the solid state were established by single crystal X-ray diffraction and all compounds except 5 show London dispersion type bismuthπ heteroarene interactions. For the bismuthine Bi(2-C4H3Se)3 (7), two polymorphs were isolated depending on the conditions of crystallization. At 8 °C, polymorph I (7a) crystallizes from an n-hexane solution in the triclinic space group P1[combining macron], whereas polymorph II (7b) crystallizes at 20 °C from a CH2Cl2/n-pentane solution in the monoclinic space group P21/c. The heteroaryl bismuthines 3 and 4 exhibit 2D network structures as a result of bismuthπ heteroarene interactions, whereas for the pyrrole derivative 6 the dispersion type interactions provide separated dimers.

SL and NW acknowledge the NRF for financial assistance (NRF grants 87788 and 95772). DIB and ZL gratefully acknowledge the National Research Foundation, South Africa (NRF 105740 and 105529), and Sasol Technology R&D Pty. Ltd, South Africa for financial support.

The reaction of ferrocenol (FcOH; Fc = Fe(C5H5)(C5H4) with aryl fluorides ArH6-nFn (n = 3 - 6) within a nucleophilic aromatic substitution reaction (SNAr) gave ferrocenyloxy-substituted fluoro benzenes of general type C6H0-3F1-5(OFc)1-5. For 1,3,5-C6H3F3 one, for 1,2,4,5-C6H2F4 two and for C6H6-nFn (n = 5,6) three F atoms could be replaced by FcO units. The reaction of 1,4-(OFc)2-C6F4 with additional amounts of FcOH afforded the tetra- and penta-substituted arenes 3,6-F2-C6(OFc)4 and C6F(OFc)5. Electrochemical investigations of both compounds showed four or five Fc/Fc+ related reversible redox processes that were attributed to electrostatic interactions. The addition of C6F6 as the electrophile after the anionic phospho-Fries rearrangement of a ferrocenyl phosphate (1,3-O->C migration) to the 1,2-substituted ortho-phosphonato ferrocenol, resulted in the formation of the respective ortho-functionalized ether. The constitution of all compounds was verified by using 19F NMR spectroscopy. Steric hindrance of the ortho-substituent resulted in a doubling of the signal sets for the C6F5 moiety in the 13C{1H} and 19F NMR spectra. The identity and substitution pattern of five compounds could also be determined by using single crystal X-ray diffraction analysis, revealing the 1,4-constitution of double functionalized derivatives, intermolecular non-classic C-HF interactions andinteractions.

The reaction of Z-FcC(Cl) CHC(O)H (Fc = Fe(η5-C5H5)(η5-C5H4)) with KI/ZnO/NH2OH·HCl gave Z-FcC(Cl) CHC N, which on further treatment with ROH/KOH (R = Me, Et, iPr, OCH2CH2OH) or H2NCH2Ph produced Z-FcC(OR) CHC N, E-FcC(NHCH2Ph) CHC N and FcC(OCH2)2CH2C N. However, the use of the sterically demanding OtBu group resulted in the elimination of HCl giving 3-ferrocenylpropynenitrile. Complex [PtCl2(N CCH C(Cl)Fc)2], as a mixture of E/Z and cis/trans isomers, was accessible by the addition of [PtCl2] to Z-FcC(Cl) CHC(O)H. When Z-FcC(OR) CHC N (R = Me; Et; iPr) was reacted with [PtCl2] in the molar ratio of 2:1, solely trans-[PtCl2(E-N CCH C(OR)Fc)2] was formed with isomerization of the C,C double bond from Z to E. These are the first examples for the entirely conversion of Z to E isomers of coordinated acrylonitriles. The stereochemistry of Z-FcC(OR) CHC N is maintained, when the Pt source is excluded, while a combination of heat and light treatment resulted in the partial isomerization. The electrochemical properties of the chloro- and the methoxy-functionalized vinyl ferrocene were studied. In the corresponding Pt complexes an anodic shift of the ferrocenyl units is observed due to an electron density transfer towards the Pt atom. Spectroelectrochemical studies of the Pt complexes allowed no definite verification that an electronic interaction between the redox-active ferrocenyl/ferrocenium termini occurs even when high ΔEp values in the cyclic indicate that two individual oxidation processes might take place in a close potential range.

(Ferrocenylthienyl)phosphines of type 2-PR2-5-Fc-cC4H2S (R = Ph (3a), tBu (3b)) and 2-PR2-3,4-Fc2-cC4HS (R = Ph (4a), tBu (4b); Fc = Fe(η5-C5H4)(η5-C5H5)) and their selenium derivatives were synthesized by consecutive synthetic methodologies. The molecular structure of 3a and 4a,b in the solid state show inter- and intramolecular (T-shaped) π–π interactions for 3a and 4a, resulting in dimeric and 1D polymeric structures. Phosphines 3a,b and 4a,b were applied in the Pd-catalyzed Suzuki-Miyaura C,C cross coupling reaction of aryl halides and boronic acids yielding the respective biaryls. Compound 3b shows a higher activity in C,C cross coupling reactions as compared to 3a and previously published thiophene-based phosphines and aminophosphines. Moreover sterically hindered and deactivated aryl bromides could be coupled at Pd loadings as low as 0.05 mol-% and at temperatures between 25 °C and 50 °C. However, the application of diferrocenylthienylphosphines 4a,b in Suzuki-Miyaura reactions resulted in decreased yields of the corresponding biaryls. In the context of electrochemical investigations on these compounds, a strong dependency of the individual electrode reactions on the phosphorus substituents were found. During UV–Vis/NIR spectroelectrochemical studies, only a very limited iron-iron electronic interaction in 4a-Se+ could be detected. Thus, 4a-Se+ corresponds to a very weak coupled class II system according to the classification of Robin and Day.

A 3D metal-organic framework (MOF) having single-molecule magnet (SMM) linkers was prepared in crystalline form by using a tetrairon(III) complex functionalised with two divergent pyridyl groups, namely [Fe4 (pPy)2 (dpm)6 ] (1; H3 pPy=2-(hydroxymethyl)-2-(pyridin-4-yl)propane-1,3-diol, Hdpm=dipivaloylmethane). Reaction of 1 with silver(I) perchlorate afforded {[Fe4 (pPy)2 (dpm)6 ]2 Ag}ClO4 (2), which crystallises in a cubic face-centred lattice and exhibits two interlocked diamondoid networks. In 2, the SMMs act as linear ditopic synthons, and silver(I) ions as tetrahedral nodes coordinated by four pyridyl nitrogen atoms. The magnetic properties of 1 (S=5 and D≈-0.4 cm(-1) in the ground spin state) are largely preserved in 2, which shows slow magnetic relaxation with an anisotropy barrier of Ueff /kB =11.46(10) K in zero field and 14.25(8) K in an applied field of 1 kOe. However, crystal symmetry triggers highly noncollinear magnetic anisotropy contributions oriented at 109.47° from each other along the threefold axes of AgN4 tetrahedra, a unique scenario fully confirmed by a single-crystal cantilever torque magnetometry investigation. Magnetisation curves down to 0.03 K demonstrated the occurrence of a wide hysteresis loop when the magnetic field was swept along one of the four Ag-N bonds. By symmetry, the crystalline compound can then be persistently magnetised parallel or antiparallel to the four main diagonals of the unit cell, although the crystals have no overall second-order anisotropy.

The spirocyclic germanium thiolates, 4H,4’H-2,2’-spirobi[benzo[d][1,3,2]dithiagermine] (1), 4H,4’H-2,2’-spirobi[benzo[d][1,3,2]oxathiagermine] (2) and 4H,4’H-2,2’-spirobi[benzo[e][1,3,2]oxathiagermine] (3) were synthesized and fully characterized. Compound 3 crystallizes as racemic conglomerate, whereas 1 and 2 give racemates in the solid state. Their reactivity towards twin polymerization (TP) was tested. The studies with regard to proton-assisted TP revealed a significantly reduced reactivity as compared to the recently reported silicon derivative, 4H,4’H-2,2’-spirobi[benzo[d][1,3,2]dioxasiline] (A). DFT−D calculations were performed for 1–3 and the model compound 4H,4’H-2,2’-spirobi[benzo[d][1,3,2]dioxagermine] (4) to evaluate the first reaction step initiating the processes of proton-assisted TP. Compound 4 with germanium bound to four oxygen atoms proved to be the most reactive precursor, but its synthesis failed. As indicated by the DFT−D calculations, compounds 1 and 2 are not suitable for TP. Starting from compound 3 a germanium and sulfur containing organic-inorganic hybrid material was obtained by thermal annealing.

A range of ferrocenyl aryl ethers of type Fc–O–Ar (Fc = Fe(η5-C5H5)(η5-C5HnX4–n); n = 2–4; X = H, P(O)(OEt)2, SO2CF3; Ar = 2,4-(NO2)2-C6H3, 4-NO2-C6H4) have been successfully prepared by using the nucleophilic aromatic substitution reaction (SNAr) of Fc–OLi (1a–Li) and electron-deficient aryl fluorides, enabling a new pathway to this rarely described family of organometallic compounds. Initial studies of 1a–Li and o-phosphonato-substituted hydroxyferrocenes (1b–Li) have also been performed, indicating a low nucleophilicity of the oxygen atom. The SNAr reaction protocol tolerates ortho substituents, e.g. phosphonato and sulfonyl groups, resulting in 1,2-X,O (X = S, P) ferrocenyl ethers that can be obtained in a one-pot synthesis procedure including 1,3-O → C anionic phospho- and thia-Fries rearrangements. Within these studies, the first 1,3-diortho-functionalized ferrocenyl aryl ether could be synthesized. An electrochemical study of the redox potentials of the obtained compounds allows conclusions on the ...

Several new diorganobismuth(III) compounds based on a butterfly-like tetrahydro-dibenzo[c,f][1,5] thiabismocine heterocyclic framework were prepared and structurally characterized. The reaction between the dilithio derivative of bis(2-bromobenzyl)sulfane with BiBr3 in a 1:1 M ratio resulted in the formation of [(C6H4CH2)2S]BiBr (1). Further exchange reactions of 1 with KI, AgNO3 and AgOSO2CF3, respectively, afforded the hypervalent species [(C6H4CH2)2S]BiX [X = I (2), ONO2 (3) and OSO2CF3 (4)]. The new species were characterized by 1H and 13C NMR, FT IR spectroscopy and mass spectrometry. The crystal and molecular structures of compounds 1–4 were determined by single-crystal X-ray diffraction. In all compounds the sulfur atom is strongly intramolecularly coordinated to bismuth, thus resulting in hypervalent species 10-Bi-4 (for 1 and 2) and 12-Bi-5 (for 3 and 4). Intermolecular interactions (X…Hmethylene in 1 and 2, Bi…Cg in 3 and Bi…O in 4) led to polymeric chains in the crystals. DFT calculations were carried out on [(C6H4CH2)2S]BiCl and 1–4 in order to better understand the S→Bi intramolecular coordination.

The structure of the title compound exhibits a trigonal (P-3) symmetry, with a C 3 axis through all three complex ions, resulting in an asymmetric unit that contains one third of the atoms present in the formula unit. Attempts to refine the solvent model were unsuccessful, indicating uninter­pretable disorder, which was handled using SQUEEZE., The structure of the title compound, [Ag(C18H15P)4]2[Ag(C6H6NO6)(C18H15P)], exhibits trigonal (P-3) symmetry, with a C 3 axis through all three complex ions, resulting in an asymmetric unit that contains one third of the atoms present in the formula unit. The formula unit thus contains two of the cations, one anion and disordered mol­ecules of methanol as the packing solvent. Attempts to refine the solvent model were unsuccessful, indicating uninter­pretable disorder. Thus, the SQUEEZE procedure in PLATON [Spek (2015 ▸). Acta Cryst. C71, 9–18] was applied, accounting for 670 electrons per unit cell, representing approximately 18 mol­ecules of methanol in the formula unit. The stated crystal data for M r, μ etc do not take these into account.

The synthesis of gold(I) complexes of 2,5-diferrocenyl-1-phenyl-1 H -phosphole ( 1 ) is presented. Chloro(2,5-diferrocenyl-1-phenyl-1 H -phosphole)gold ( 3 ) has successfully been prepared by the reaction of 1 with AuCl(SMe 2 ) ( 2 ). Treatment of 2 with arylethyne (aryl = ferrocenyl, phenyl) using catalytical amounts of [CuI] and 1 equiv. of 1 gave arylethynyl-(2,5-diferrocenyl-1-phenyl-1 H -phosphole)gold 4a and 4b (aryl: a = ferrocenyl; b = phenyl). Compound [ μ -(1,4-phenylenedi-2,1-ethynediyl)]bis(2,5-diferrocenyl-1-phenyl-1 H -phosphole)digold ( 5 ) could be synthesized by a similar procedure using 0.5 equiv. of 1,4-diethynylbenzene. The electrochemical properties of 3 , 4a,b and 5 were investigated by cyclic and square wave voltammetry. In 3 , 4a and 4b each ferrocenyl unit shows one reversible redox event with redox separations of the ferrocenyl moieties in 2,5 position of approximately 260 mV. In 5 two redox events for the four ferrocenyl groups were observed. Spectroelectrochemical measurements of 3 , 4a and 4b reveal IVCT absorptions with intensities of 1100–1300 L mol −1 cm −1 and a full-width-at-half-height of ≈3650 cm −1 . In 5 two mixed-valent units are present per molecule and therefore, the intensity of the IVCT band is increased to 2700 L mol −1 cm −1 . Compounds 3 , 4a,b and 5 can be classified as moderately coupled class II systems according to Robin and Day. The complexation of the gold(I) fragment by the phosphorus atom leads to a decreased metal–metal interaction when compared to 1 .

The mol­ecular structure of the distorted trigonal–planar-coordinated tetra­kis­(tri­phenyl­phosphan­yl)disilver salt of butane-1,1,4,4-tetra­carb­oxy­lic acid is reported, present as a di­chloro­methane tris­olvate. The coordination complex exhibits an inversion centre through the CH2—CH2 bond and inter­molecular T-shaped π–π inter­actions between the phenyl rings of the PPh3 substituents, forming a ladder-type superstructure parallel to the b axis., The mol­ecular structure of the tetra­kis(tri­phenyl­phosphan­yl)disilver salt of butane-1,1,4,4-tetra­carb­oxy­lic acid, [Ag2(C8H8O8)(C18H15P)4]·3CH2Cl2, crystallizes with one and a half mol­ecules of di­chloro­methane in the asymmetric unit. The coordination complex exhibits an inversion centre through the central CH2—CH2 bond. The AgI atom has a distorted trigonal–planar P2O coordination environment. The packing is characterized by inter­molecular T-shaped π–π inter­actions between the phenyl rings of the PPh3 substituents in neighbouring mol­ecules, forming a ladder-type superstructure parallel to [010]. These ladders are arranged in layers parallel to (101). Intra­molecular hydrogen bonds between the OH group and one O atom of the Ag-bonded carboxyl­ate group results in an asymmetric bidendate coordination of the carboxyl­ate moiety to the AgI ion.

Despite extensive years of research, the direct oxidation of the 7,8-double bond of opioids has so far received little attention and knowledge about the effects of this modification on activity at the different opioid receptors is scarce. We herein report that potassium permanganate supported on iron(II) sulfate heptahydrate can be used as a convenient oxidant in the one-step, heterogeneous conversion of Delta(7.8)-opioids to the corresponding 7 beta-hydroxy-8-ketones. Details of the reaction mechanism are given and the effects of the substituent at position 6 of several opioids on the reaction outcome is discussed. The opioid hydroxy ketones prepared are antagonists at the mu- and delta-opioid receptors. Docking simulations and detailed structure-activity analysis revealed that the presence of the 7 beta-hydroxy-8-ketone functionality in the prepared compounds can be used to gain activity towards the delta opioid receptor. The 7 beta-hydroxy-8-ketones prepared with this method can also be regarded as versatile intermediates for the synthesis of other opioids of interest. (C) 2018 Elsevier Masson SAS. All rights reserved.

The synthesis of germanium(II) 2-tert-butyl-4-methyl-6-(oxidomethyl)phenolate (1) starting from Ge[N(SiMe3)2]2 and the corresponding salicyl alcohol is reported. Compound 1 undergoes an intramolecular oxidative insertion reaction of germanium into a C–O bond to result in a cyclic germanium(IV) tetraoxidogermocane (2). Addition of 3-tert-butyl-2-hydroxy-5-methylbenzyl alcohol to either compound 1 or 2 gave a spirocyclic monoorgano dioxagermine (3). The results of 1H NMR spectroscopic studies and DFT-D calculations are in agreement with the proposed reaction cascade in which the novel germylene 1 is first converted into the germocane 2 followed by reaction with 3-tert-butyl-2-hydroxy-5-methylbenzyl alcohol to finally provide compound 3. Addition of 4-(dimethylamino)pyridine to a solution of germylene 1 resulted in the formation of an air-stable monomeric 1:1 complex (4). The characterization of compounds 1–4 by single-crystal X-ray diffraction analysis, thermal analysis, and 1H NMR, 13C{1H} NMR, and ATR-FTIR spectroscopy is presented.

Germanium(II) (2-methoxyphenyl)methoxide (1) and [W(CO)5(thf)] gave rise reproducibly (79 % yield) to a new, uncharged transition-metal complex of a germanium(II) hydroxido oxido cluster – [{Ge4(μ-O)2(μ-OH)4}{W(CO)5}4]·4THF (2·4THF) – as a product of hydrolysis. The germylene 1 is monomeric in solution at ambient temperature but forms dimers in solution at low temperatures and in the solid state. Dimerization of compound 1 was studied by 1H NMR spectroscopy and with the aid of DFT-D calculations. The tetranuclear cluster 2 shows an adamantane-like core structure with coordination of tungsten pentacarbonyl to germanium(II) in the solid state as well as in solution. Characterization of both compounds, including by single-crystal X-ray diffraction analysis, by 1H NMR, 13C{1H} NMR, FTIR spectroscopy, and through thermal analyses, is presented.

Pentacarbonyl(2,5-diferrocenyl-1-phenyl-1H-phosphole)metal complexes 3a–c (3a, M = Cr; 3b, M = Mo; 3c, M = W) have successfully been synthesized by the reaction of 2,5-diferrocenyl-1-phenyl-1H-phosphole (1) with M(CO)5(thf) (2a, M = Cr; 2b, M = Mo; 2c, M = W). Further irradiation of 3a–c with 1 equiv of 1 in tetrahydrofuran leads to tetracarbonylbis(2,5-diferrocenyl-1-phenyl-1H-phosphole)metal complexes 4a–c (4a, M = Cr; 4b, M = Mo; 4c, M = W). In addition, the reaction of 1 with Fe2(CO)9 gave tetracarbonyl(2,5-diferrocenyl-1-phenyl-1H-phosphole)iron (6) and heptacarbonyl[μ-(2,3,4,5-η)-1-(2,5-diferrocenyl-1-phenyl-1H-phosphole)]diiron (7), respectively. Treatment of 2,5-diferrocenyl-1-phenyl-1H-phosphole sulfide (8) with Fe2(CO)9 afforded tricarbonyl[(2,3,4,5-η)-(2,5-diferrocenyl-1-phenyl-1H-phosphole 1-sulfide)]iron (9). Complexes 3b,c, 4c, 7, and 9 have been characterized by single-crystal X-ray diffraction. Molecules 3b,c and 4c exhibit a distorted-octahedral geometry, whereas in 4c the two phosphole u...

A series of 3,4-di-N-substituted 2,5-diferrocenyl thiophenes is reported with the aim to explore the electronic interaction between the organometallic termini over their bridging unit. The syntheses of thiophenes 1–4 were implemented on the basis of 2,5-diferrocenyl-3,4-dinitrothiophene (1), which is accessible within a Pd-promoted Suzuki–Miyaura C,C cross-coupling reaction. Reduction of the nitro functionalities and a subsequent methylation or condensation reaction gives 2,5-diferrocenyl-3,4-bis(N,N-dimethylamino)-thiophene (2) or 5,7-diferrocenylthieno[3,4-b]pyrazine (3). Finally, 5,7-diferrocenyl-1,4-dimethyl-1,2,3,4-tetrahydrothieno[3,4-b]pyrazine (4) could be synthesized through conversion of 3 in a two-step reduction/methylation reaction. The spectroscopic characterization of 1–4 was complemented by the investigation of their structural properties in the solid state. The latter disclose no significant influence of the electronically different N substituents on the thiophene bond distances and angles...

2-(3-Ferrocenylthienyl)phosphines of type 2-PR2-3-Fc-cC4H2S (R = tBu (2); R = Ph (3); Fc = Fe(η5-C5H4)(η5-C5H5)) were synthesized and the structures of 2 and 3 in the solid state were determined by single X-ray structure analysis. Inter- and intra-molecular T-shaped π⋯π stackings involving cyclopentadienyl and phenyl rings are characteristic for 3. The application of 2 and 3 as ligands in the Pd-catalyzed Suzuki–Miyaura C,C cross-coupling of aryl halides with boronic acids to give the respective biaryls is reported. Electron-rich, electron-poor and sterically hindered substrates could be coupled with high yields at Pd-loadings as low as 0.1 mol%.

Reactions of alkyl aryl sulfoxides H–CRR′S(O)Ar with n-BuLi–TMEDA (TMEDA = N,N,N′,N′-tetramethylethylenediamine) afforded α-sulfinyl functionalized alkyl aryl lithium compounds of the type [Li2{CRR′S(O)Ar}2(TMEDA)2] (1, R/R′ = H/H, Ar = Ph; 2, R/R′ = H/H, Ar = p-Tol; 3, R/R′ = Me/Me, Ar = Ph; 4, R/R′ = H/Ph, Ar = Ph; 5, R/R′ = Me/Ph, Ar = Ph). The compounds were characterized by 1H, 13C and 7Li NMR spectroscopy and, except for 5, by single-crystal X-ray diffraction analyses. In crystals of 1, 2, 3 and 4·Et2O dinuclear molecules with four-membered Li2O2 rings were found. There are no Li⋯Cα contacts, thus, “free” carbanions are the main structural feature. Reactions of 1–6 (6, R/R′ = H/Me, Ar = Ph) with benzaldehyde and benzophenone afforded the corresponding sulfoxides of the type ArS(O)CRR′CHPhOH (1a–6a) and ArS(O)CRR′CPh2OH (1b–6b), respectively. The reactions yielding 1a/3a and 4b/6b proceeded with high diastereoselectivities. By X-ray diffractometry it has been shown that in the case of 3a and 4b the diastereomers consisting of the two enantiomers SSRC and RSSC were formed.

Temperature-dependent anionic phospho-Fries rearrangements of ferrocenyl/phenyl phosphates P(O)(OFc)n(OPh)3 − n (Fc = Fe(η5-C5H5)(η5-C5H4); n = 0,1,2,3) were investigated. Whereas ferrocenyls solely undergo one rearrangement per reaction step, the number of phenyl-based 1,3-O → C shifts depends on the temperature. This results in different types of otherwise hardly accessible mixed ferrocenyl/phenyl organophosphorus compounds. Detailed investigations of the triple-rearrangement of triphenyl phosphate (n = 0) reveals a consecutive formation of its phosphonate and phosphinate prior to the known phosphane oxide.

A straightforward design of receptors for binding and sensing of sulfate in aqueous medium was developed. The design involves the connection of two naphthalimide-based pH probes through a hydrogen-bonding motif. The structure of the receptor-sulfate complex, predicted by DFT calculations, was unambiguously confirmed by NMR measurements. There are three major interactions stabilizing the host-guest complex: electrostatic interactions, hydrogen bonding, and stacking interactions of the dyes. Study of two control receptors containing either one dye or methyl amide groups instead of amides, revealed that electrostatic and hydrogen bonding interactions contribute the most to affinity and selectivity of receptors. The receptors can detect sulfate in a 1:1 THF-buffer mixture in pH window 3.6-4.5 demonstrating up to 7-fold fluorescence enhancement. To the best of our knowledge, the reported PET (photoinduced electron transfer) anion probes possess the largest response for sulfate in aqueous solution yet described.

The synthesis of 1,1'-bis(thymine)ferrocene nucleoside is reported. This nucleoside was obtained in a two-step synthetic methodology including a Michael addition reaction of 1,1'-bis(3-chloropropionyl)ferrocene with thymine to afford the bis(thymine) adduct in 44 % yield. In the second step, the two prochiral carbonyl functionalities in the Michael adduct were reduced to hydroxyl groups with sodium borohydride. This apparently straightforward reaction proceeds in a highly stereoselective fashion to yield the title ferrocenyl nucleoside as a racemic mixture that consists of the R,R and the S,S isomers. The absolute configuration of the chiral carbon atoms in the nucleoside was assigned on the basis of single-crystal X-ray diffraction analysis of the methyl derivative. Furthermore, the mechanism of reduction of the bis(thymine) adduct was investigated by using DFT calculations. The two critical minima, pre-reactive complex, and semi-reduced intermediate, as well as two corresponding transition states were located to support the observed stereoselectivity. The redox properties of 1,1'-bis(thymine)ferrocene nucleoside, its precursor, and congeners were investigated using cyclic voltammetry. For the title compound a reversible redox process was found at a low potential of -30 mV versus FcH/FcH

Various new thio- and selenosulfonato complexes of iron were synthesized by straight forward route. Treatment of the iron chalcogenides, (μ-Ex)[CpFe(CO)2]2 (E = S; x = 2–4, E = Se; x = 1) with sulfonyl chlorides produced the corresponding thio- or selenosulfonato complexes CpFe(CO)2ESO2Ar [Ar = 2-C4H3S (1), 5-C4H2SCl (2), 1,3-C6H4SO2Cl (3), 1,3-C6H4CO2H (4); E = S (a), Se (b)]. The dimers [CpFe(CO)2ESO2]2(1,3-C6H4) (5) are obtained from the iron chalcogenides with 1,3-C6H4(SO2Cl)2 in a 2:1 molar ratio. All of these new complexes have been characterized by IR, 1H, 13C NMR spectroscopy, UV–Vis and elemental analysis. The X-ray structure of CpFe(CO)2ESO2-1,3-C6H4SO2Cl (3a) is determined.

Treatment of allenyl isothiocyanate with a variety of nucleophiles leads to 5-methylthiazoles with a functional group at the 2-position. The same pattern of reactivity is also seen with N-aminophthalimide. In the presence of azide salt, hydrazoic acid, or N,N-disubstituted hydroxylamines, however, allenyl isothiocyanate is converted into bifunctionalized thiazoles. We explain the formation of these products by nucleophilic addition at the isothiocyanato moiety followed by ring closure and an N–N or N–O cleavage reaction to generate short-lived 2-imino-5-methylidenethiazole or 5-methylidenethiazol-2-one. Such intermediates are trapped by addition reactions to give the final heterocyclic compounds. In the case of N,N-disubstituted hydroxylamines, the primary addition products with allenyl isothiocyanate can be detected as unstable intermediates by IR and NMR spectroscopy.

Within a series of α,α′-diferrocenylthiophenes, the influence of electron-withdrawing substituents at the ferrocenyl moieties and electron-donating functionalities at the thiophene bridge on the electronic behavior was studied. The synthesis of the appropriate 2,5-fc2-cC4H2S and 2,5-fc2-3,4-(OCH2CH2O)-cC4S compounds (fc = Fe(η5-C5H4)(η5-C5H4R); R = H (1, 5), 3,5-(CF3)2-cC6H3 (2, 6), CHO (3, 7), C≡N (4, 8)) was carried out using the Negishi C,C cross-coupling protocol to effect the coupling of the thiophene and the ferrocenyl moieties. The corresponding diferrocenylthiophenes were characterized spectroscopically. Within this context, the structural properties of 2–5, [5][B(C6F5)4], 6, and 8 in the solid state were investigated by single-crystal X-ray diffraction studies. Electrochemical investigations of thiophenes 2–8 demonstrated an increasing redox separation and hence thermodynamic stability of the corresponding mixed-valent species in the series 1 < 3 < 5 < 4 ≈ 2 < 6 < 7 < 8. Moreover, UV/vis/near-IR ...

The synthesis of 3,4-diferrocenyl-substituted pyrroles of the type 3,4-Fc2-cC4H2NR [Fc = Fe(η5-C5H4)(η5-C5H5); R = Ph (3a), SO2-4-MeC6H4 (Ts) (3b), SiiPr3 (3c)], 3,4-(FcC≡C)2-cC4H2NR [R = Ph (4a), Ts (4b)], and 3-Br-4-FcC≡C-cC4H2NR [R = Ph (7a), Ts (7b)] from 3,4-Br2-cC4H2NR [R = Ph (2a), Ts (2b), SiiPr3 (2c)] is discussed. The molecular structures of 3a,b, 5, 4b, and 7b in the solid state are reported and show that the formal double bonds in the heterocyclic core are rather localized relative to pyrrole itself. The investigations with (spectro)electrochemical methods reveal the different capabilities for the formation of mixed-valent species and allows the classification of 3a,b as class II systems, whereas compounds that feature electron-withdrawing –C≡C– units (4a,b) can be assigned to class I systems according to Robin and Day.

Neutral iridium(III) complexes of the type [Ir(η(5)-C₅Me₅)Cl₂{Ph₂PCH₂S(O)xPh-κP}] (1-3) with diphenylphosphino-functionalized methyl phenyl sulfides, sulfoxides, and sulfones Ph₂PCH₂S(O)xPh (x = 0, L1; 1, L2; 2, L3) and the cationic complex [Ir(η(5)-C₅Me₅)Cl{Ph₂PCH₂SPh-κP,κS}][PF6] (4) were synthesized and fully characterized analytically and spectroscopically. Furthermore, the structure of 2 was determined by X-ray diffraction analysis. The biological potential of the neutral and cationic iridium(III) complexes was tested in vitro against the cell lines 8505C, A253, MCF-7, SW480 and 518A2. Complex [Ir(η(5)-C₅Me₅)Cl₂{Ph₂PCH₂S(O)Ph-κP}] (2), with ligand L2 κP coordinated containing a pendent sulfinyl group, is the most active one (IC₅₀ values of about 3 μM), thus, with activities comparable to cisplatin. Complex 2 proved to have an even a higher antiproliferative activity than cisplatin against 8505C and SW480 cell lines, used as a model system of highly anaplastic cancers with low sensitivity to conventional chemotherapeutics such as cisplatin. Additional experiments demonstrated that apoptosis and autophagic cell death contribute to the drug's tumoricidal action.

A series of (oligo)pyrroles featuring redox-active terminal ferrocenyl groups (Fc2-(cC4H2NPh)n (4, n = 1; 9, n = 2; 16, n = 3; 20, n = 4)) has been prepared using a Negishi C,C cross-coupling reaction protocol. The bi-, ter-, and quaterpyrrole wire moieties have been built up by C,C cross-coupling reactions of trimethylsilyl-protected pyrrole units in the presence of [Pd(CH2C(CH3)2P(tC4H9)2)(μ-Cl)]2 as precatalyst. The structural properties of the title compounds were investigated by spectroscopic means and single-crystal X-ray diffraction studies (9, 16, and 20). The influence of the increasing number of N-phenylpyrrole units on the electronic interaction between the iron centers was studied using electrochemistry (cyclic (CV) and square wave voltammetry (SWV)) as well as spectroelectrochemistry (in situ UV/vis/near-IR spectroscopy). With the exception of the diferrocenyl quaterpyrrole 20, the application of [NnBu4][B(C6F5)4] as electrolyte allows the discrete oxidation of the ferrocenyl termini (ΔE°′ = ...

The synthesis, properties and characterization of a series of 2,5-bis(pyridyl)pyrazine-based heterobi-(PtM) (5, 6), tri-(Pt2M) (8) and tetra-nuclear (Ti2M2) (10) (M = Cu, Ag) transition metal complexes is reported using [(bppz)Pt(C CSiMe3)2] (2) (bppz = 2,5-bis(pyridyl)pyrazine), {[Ti](μ-σ,π-C CSiMe3)2}MX (9a, M = Cu, X = FPF5; 9b, M = Ag, X = OClO3; [Ti] = (η5-C5H4SiMe3)2Ti) and diverse copper(I) and silver(I) salts as key starting materials. Treatment of 2 with equimolar amounts of [Cu(N CMe)4]X (3a, X = BF4; 3b, X = OTf( OSO2CF3)) or [MX] (M = Cu: 3c, X = Br; M = Ag: 4a, X = ClO4; 4b, X = O2CCF3; 4c, X = NO3) gave heterobimetallic [(bppz)Pt((μ-σ,π-C CSiMe3)2MX)] (M = Cu: 5a, X = FBF3; 5b, X = OTf; 5c, X = Br. M = Ag: 6a, X = OClO3; 6b, X = O2CCF3; 6c, X = ONO2), while a 1:2 stoichiometry of, for example, 2:3a and 2:4a, respectively, produced trimetallic {[(bppz)Pt(μ-σ,π-C CSiMe3)2]2M}X (8a, M = Cu, X = BF4; 8b, M = Ag, X = ClO4). Molecules 8a and 8b are also accessible, when 5a or 6a were reacted with 2 in a 1:1 molar ratio. In 8a and 8b two (bppz)Pt(C CSiMe3)2 tweezer moieties are connected by M+ ions thus resulting in a pseudo-tetrahedral environment about M+. Complexes of general composition [([Ti](μ-σ,π-C CSiMe3)2M)2(bppz)][X]2 (10a, M = Cu, X = PF6; 10b, M = Ag, X = ClO4) were accessible by treatment of {[Ti](μ-σ,π-C CSiMe3)2}MX (9a, M = Cu, X = FPF5; 9b, M = Ag, X = OClO3) with 0.5 equivalents of bppz. The structure of 10b in the solid-state shows that bppz acts as connectivity for the bridging of two {[Ti]((μ-σ,π-C CSiMe3)2)Ag}+ building blocks, whereby the planar bppz unit is almost perpendicular oriented towards the Ti–Ag organometallic π-tweezer groups. Cyclic voltammetry measurements reveal that upon reduction of 5, 6 and 10 decomposition of these complexes occurs upon formation of elemental M and non-coordinated (bppz)Pt(C CSiMe3)2 and [Ti](C CSiMe3)2, respectively.

The synthesis of a series of carbosilanes of type 1-Br–C6H4–4-SiMe3–n(CH2CH=CH2)n (n = 1, 2, 3), Si[C6H4–4-SiMe3–n(CH2CH=CH2)n]4, 1-Br–C6H4-4-Si[C6H4–4-SiMe3–n(CH2CH=CH2)n]3 (n = 0, 1, 2, 3), ClSi[C6H4–4-Si{C6H4–4-SiMe3–n(CH2CH=CH2)n}3]3, Si[C6H4–4-Si{C6H4–4-SiMe3–n(CH2CH=CH2)n}3]4 (n = 1, 2), and 1-Br–C6H4–4-Si[C6H4–4-Si{C6H4–4-SiMe3–n(CH2CH=CH2)n}3]3 (n = 0, 1, 2, 3) is discussed. The structures of Si[C6H4–4-SiMe2(CH2CH=CH2)]4 (7b) and ClSi[C6H4–4-Si{C6H4–4-SiMe2(CH2CH=CH2)}3]3 (10a) in the solid state are reported. The crystal structures of both dendrimers are based on C–H···πCC (πCC = double bond of the CH=CH2 groups) and π–π interactions. The 3D network structure observed for 7b is composed of three crystallographically independent head-to-head stacking columns along the crystallographic b axis with π–π contacts among the C6H4 groups of neighboring molecules, with the columns interacting further by C–H···πCC arrangements. Two molecules of 10a interdigitate in the solid state to form self-complementary dimers that are stabilized by C–H···πCC and π–π contacts. The structures of the monomer and the dimer were optimized by using the MM+ force field as implemented in HyperChem 4.02. In addition, the presence of self-complementary structures in solution is evidenced from 1H NMR spectroscopy. In dichloromethane solely dimeric species exist, whereas in benzene monomers are observed. Calculated electrostatic potentials were used to rationalize the supramolecular structures of these two carbosilane compounds.

A series of 11 cymantrene and cyrhetrene nucleobase conjugates, together with the hitherto unreported N7 isomer of a ferrocene–adenine conjugate were synthesised and characterised. The synthetic approach involved a Michael addition reaction of in-situ-generated acryloylcymantrene, acryloylcyrhetrene and acryloylferrocene with the canonical nucleobases thymine, uracil and adenine. The mechanism of these reactions was investigated by means of density functional theory calculations. The products were characterised by spectroscopic and electrochemical methods. The molecular structure of one cymantrene–adenine conjugate in the solid state was determined by single-crystal X-ray structure analysis, confirming the N9-substitution of the adenine moiety. It was found that the molecule adopts a bent conformation with the adenine and cyclopentadienyl planes in almost perpendicular orientation. The cymantrenyl nucleobases showed an irreversible redox behaviour, which is associated with ligand-exchange reactions of the radical cationic species. The newly synthesised compounds were also tested for their activity against the protozoan parasite Trypanosoma brucei and human myeloid leukaemia HL-60 cells. Some compounds showed promising antitrypanosomal activity, and most of them were non-toxic to HL-60 cells. It was also found that cymantrene and cyrhetrene ketone nucleobases were more active than their alcohol congeners. These findings indicate the potential of cymantrenyl and cyrhetrenyl nucleobase conjugates as possible lead compounds for future antitrypanosomal drug development.

The reaction of different metallocene fragments [Cp(2)M] (Cp=η(5)-cyclopentadienyl, M=Ti, Zr) with diferrocenylacetylene and 1,4-diferrocenylbuta-1,3-diyne is described. The titanocene complexes form the highly strained three- and five-membered ring systems [Cp(2)Ti(η(2)-FcC(2)Fc)] (1) and [Cp(2)Ti(η(4)-FcC(4)Fc)](2) (Fc=[Fe(η(5)-C(5)H(4))(η(5)-C(5)H(5))]) by addition of the appropriate alkyne or diyne to Cp(2)Ti. Zirconocene precursors react with diferrocenyl- and ferrocenylphenylacetylene under C-C bond coupling to yield the metallacyclopentadienes [Cp(2)Zr(C(4)Fc(4))](3) and [Cp(2)Zr(C(4)Fc(2)Ph(2))](5), respectively. The exchange of the zirconocene unit in 3 by hydrogen atoms opens the route to the super-crowded ferrocenyl-substituted compound tetraferrocenylbutadiene (4). On the other hand, the reaction of 1,4-diferrocenylbuta-1,3-diyne with zirconocene complexes afforded a cleavage of the central C-C bond, and thus, dinuclear [{Cp(2)Zr(μ-η(1):η(2)-C≡CFc)}(2)] (6) that consists of two zirconocene acetylide groups was formed. Most of the complexes were characterized by single-crystal X-ray crystallography, showing attractive multinuclear molecules. The redox properties of 3, 5, and 6 were studied by cyclic voltammetry. Upon oxidation to 3(n+), 5(n+), and 6(n+) (n=1-3), decomposition occured with in situ formation of new species. The follow-up products from 3 and 5 possess two or four reversible redox events pointing to butadiene-based molecules. However, the dinuclear complex 6 afforded ethynylferrocene under the measurement conditions.

A series of methoxyphenyl substituted chelated bis-N-heterocyclic carbene palladium(II) complexes has been synthesized and characterized by cyclovoltammetry, spectroscopy (NMR, IR), solid state structures and investigated by quantum chemical calculations. The results confirm that a methoxy functionality in para position at the aryl substituent enhances the donor properties of the ligand compared to a methoxy group in ortho or meta position.

The heterotrimetallic complex 1,1′-[Fc(SeRuCp(PPh3)2)2] is accessible by the reaction of 1,1′-[Fc(SeLi)2·2THF] (Fc = Fe(η5-C5H4)2, THF = Tetrahydrofuran) with two equivalents of CpRu(PPh3)2Cl in high yield. Complex 1,1′-[Fc(SeLi)2·2THF] can be prepared by treatment of 1,1′-[Fc(SeSiMe3)2] with two equivalents of n-BuLi in THF solution. 1,1′-[Fc(SeRuCp(PPh3)2)2] is converted to 1,1′-[Fc(SeRuCpCO(PPh3))2] under CO atmosphere in THF solution. The complexes 1,1′-[Fc(SeRuCp(PP))2] [PP = Ph2P(CH2)PPh2 (dppm), Ph2P(CH2)2PPh2 (dppe), Ph2P(CH=CH)2PPh2 (dppee), Ph2P(CH2)3PPh2 (dppp)] are obtained in a one-pot reaction of CpRu(PPh3)2Cl and 1,1′-[Fc(SeLi)2·2THF] with the chelating bisphosphine ligand.

The synthesis of a series of (ethynylferrocenyl)phosphino ruthenium compounds of type (FcC C)R 2 P(RuCl 2 ( η 6 - p -cymene)) ( 3a , R = C 6 H 5 ; 3b , R = 2-CH 3 C 6 H 4 ; 3c , R = c C 4 H 3 O; 3d , R = t -Bu; 3e , R = c C 6 H 11 ; p -cymene = 1- i C 3 H 7 -4-CH 3 -C 6 H 4 ; Fc = Fe( η 5 -C 5 H 4 )( η 5 -C 5 H 5 )) and (RuCl 2 ( η 6 - p -cymene))(FcC C)P(C CPPh 2 (RuCl 2 ( η 6 - p -cymene))) 2 ( 10 ) resulting from the addition of ferrocenylphosphines P(C CFc)R 2 ( 1a – 1e ) or P(C CFc)(C CPPh 2 ) 2 ( 9 ) to [RuCl 2 ( η 6 - p -cymene)] 2 ( 2 ) is described. The structures of 3b , 3c and 10 in the solid state are reported confirming the expected tetrahedral coordination sphere about the phosphorus atom as well as the “piano-stool” arrangement about the ruthenium atom(s). Ruthenium complexes 3 and 10 are catalytically active under mild conditions in the alkyne-to-carboxylic acid coupling as it was shown for the reaction of propargyl alcohol with benzoic acid. A comparison with literature known [RuCl 2 (PR 3 )( η 6 - p -cymene)] catalysts is presented.

The reaction of [Bi(22)O(26)(OSiMe(2)tBu)(14)] (1) in THF with salicylic acid gave [Bi(22)O(24)(HSal)(14)] (2) first, which was converted into [Bi(38)O(45)(HSal)(22)(OH)(2)(DMSO)(16.5)]·DMSO·H(2)O (3·DMSO·H(2)O) after dissolution and crystallization from DMSO. Single-crystal X-ray diffraction analysis and ESI mass spectrometry associated with infrared multi-photon dissociation (IRMPD) tandem MS experiments confirm the formation of the large and quite stable bismuth oxido cluster 3. The reaction of compound 2 with the butoxycarbonyl(BOC)-protected amino acids phenylalanine and valine (BOC-PheOH and BOC-ValOH), respectively, resulted in the formation of chiral [Bi(38)O(45)(BOC-AA)(22)(OH)(2)] (AA=deprotonated amino acid), as shown by a combination of different analytical techniques such as elemental analysis, dynamic light scattering, circular dichroism spectroscopy, and ESI mass spectrometry.

Protein kinase C (PKC) is a widely studied molecular target for the treatment of cancer and other diseases. We have approached the issue of modifying PKC function by targeting the C1 domain in the regulatory region of the enzyme. By using the X-ray crystal structure of the PKCδ C1b domain combined with molecular modeling, we discovered (3-aminodecahydro-1,4-methanonaphthalen-2-yl)methanol as a novel C1 domain ligand. The stereoselective synthesis of this tricyclic γ-amino alcohol was based on two successive Diels–Alder reactions to construct the six continuous stereocenters of the key intermediate.

2,5-Diferrocenyl-1,3,4-thiadiazole, 2,5-Fc2-cC2N2S, (3) has been synthesized by a two-fold Negishi ferrocenylation of dibromothiadiazole (1) with FcZnCl (2) (Fc = Fe(η5-C5H4)(η5-C5H5)) in presence of [Pd(Ph3P)4] as catalyst. Additional spacer units between the ferrocenyls and the cC2N2S core could be introduced by using the Sonogashira C,C cross-coupling protocol. Reaction of 2,5-Br2-cC2N2S (1) or 2,5-(C6H4-4′-I)2-cC2N2S (6) with FcC CH (4) using [PdCl2(Ph3P)2] and [CuI] as catalyst produced the appropriate organometallics 2,5-(FcC C)2-cC2N2S (5) or 2,5-(C6H4-4′-C CFc)2-cC2N2S (7). The electronic and structural properties of 3, 5, and 7 were investigated with UV–Vis spectroscopy and single crystal X-ray diffraction (3). Complex 3 adopts a solid state structure with none of the ferrocenyl substituents being coplanar with the thiadiazole ring. Cyclic, square wave, linear sweep voltammetry and in-situ NIR spectro-electrochemistry highlight the electrochemical properties of 3. In dichloromethane (0.1 mol L−1 [N(nBu)4][B(C6F5)4]), compound 3 displays two well resolved electrochemical reversible one-electron events with formal reduction potentials of 0.192 and 0.338 V versus FcH/FcH+. In contrast, in presence of [N(nBu)4][PF6], the thiadiazoles 3 (E0 = 0.22 V), 5 (E0 = 0.18 V) and 7 (E0 = 0.09 V) show simultaneously oxidation of the two ferrocenyl termini versus FcH/FcH+. Spectro-electrochemical studies, performed in a dichloromethane solution of 0.2 mol L−1 [N(nBu)4][B(C6F5)4], also show that 3 can successively be oxidized via 3+ to 32+. A weak IVCT absorption (e ca. 300 L mol−1 cm−1) at 1560 nm was found and is consistent with appreciable interactions between neutral ferrocenyl and positively charged ferrocenium mixed valent intermediates. Mixed-valent compound 3+ corresponds to a class II molecule according to Robin and Day.

The reaction of Fe2(CO)9 with Bi(OSiMe2tBu)3 gave soluble [(CO)4FeBi(OSiMe2tBu)]2 (1) in moderate yield whereas in case of Bi(OtBu)3 used as starting material both [(CO)4FeBi(OtBu)]n (2) and the bismuth–iron cluster [(CO)3FeBi3(OtBu)4{OCO(OtBu)}]2 (3) were isolated. The latter forms upon insertion of CO2, released during reaction of diiron nonacarbonyl with bismuth tert-butoxide, into a Bi–OtBu bond. The compounds were characterized by IR and 1H NMR spectroscopy as well as thermogravimetric analyses. Additionally, the molecular structures of compounds 1 and 3 were elucidated by single crystal X-ray diffraction. The core structure of [(CO)4FeBi(OSiMe2tBu)]2 (1) is build up by a four-membered Bi2Fe2 ring whereas [(CO)3FeBi3(OtBu)4{OCO(OtBu)}]2 (3) is composed of two tetrahedral FeBi3 cluster cores that dimerise via bridging –OCO(OtBu) ligands. Analysis of the TGA residues by PXRD revealed that compound 2 is the best precursor for multiferroic BiFeO3 among the compounds studied here, although Bi25FeO39 was detected as minor impurity.

The synthesis and characterization of novel amidoamine-based metallodendrimers with heterobimetallic end-grafted amidoferrocenyl-palladium-allyl chloride units is described. Dendrimer (Fe((η 5 -C 5 H 4 PPh 2 )(η 5 -C 5 H 4 ))C(O)HNCH 2 CH 2 NHC(O)CH 2 CH 2 )N[CH 2 CH 2 N(CH 2 CH 2 C(O)NHCH 2 CH 2 NH-C(O)(Fe(η 5 -C 5 H 4 )(η 5 -C 5 H 4 PPh 2 ))) 2 ] 2 ( 9 - Fe ) and the corresponding metal species (Fe((η 5 -C 5 H 4 PPh 2 (Pd(η 3 -C 3 H 5 )Cl))(η 5 -C 5 H 4 ))C(O)HNCH 2 CH 2 NHC(O)CH 2 CH 2 )N[CH 2 CH 2 N(CH 2 CH 2 C(O)NHCH 2 CH 2 NHC(O)(Fe(η 5 -C 5 H 4 )(η 5 -C 5 H 4 PPh 2 (Pd(η 3 -C 3 H 5 )Cl)))) 2 ] 2 ( 9 - Fe – Pd ) were prepared by a consecutive divergent synthesis methodology including addition–amidation cycles, standard peptide coupling, and coordination procedures. For comparative reasons also the monomeric and dimeric molecules (Fe(η 5 -C 5 H 4 PPh 2 )(η 5 -C 5 H 4 C(O)NH n C 3 H 7 )) ( 5 - Fe ) and [Fe(η 5 -C 5 H 4 PPh 2 )(η 5 -C 5 H 4 C(O)NHCH 2 )] 2 ( 6 - Fe ) as well as N(CH 2 CH 2 C(O)NHCH 2 CH 2 NHC(O)(Fe(η 5 -C 5 H 4 )(η 5 -C 5 H 4 PPh 2 ))) 3 ( 7 - Fe ) and [CH 2 N(CH 2 CH 2 C(O)NHCH 2 CH 2 NHC(O)(Fe(η 5 -C 5 H 4 )(η 5 -C 5 H 4 PPh 2 ))) 2 ] 2 ( 8 - Fe ) were prepared from Fe(η 5 -C 5 H 4 PPh 2 )(η 5 -C 5 H 4 CO 2 H) ( 3 ). Using [Pd(η 3 -C 3 H 5 )Cl] 2 ( 4 ) as palladium source heterobimetallic metallodendrimers (Fe(η 5 -C 5 H 4 PPh 2 (Pd(η 3 -C 3 H 5 )Cl))(η 5 -C 5 H 4 C(O)NH n C 3 H 7 )) ( 5 - Fe – Pd ), [Fe(η 5 -C 5 H 4 PPh 2 (Pd(η 3 -C 3 H 5 )Cl))(η 5 -C 5 H 4 C(O)NHCH 2 )] 2 ( 6 - Fe – Pd ), N(CH 2 CH 2 C(O)NHCH 2 CH 2 NHC(O)(Fe(η 5 -C 5 H 4 )(η 5 -C 5 H 4 PPh 2 (Pd(η 3 -C 3 H 5 )Cl)))) 3 ( 7 - Fe – Pd ) and [CH 2 N(CH 2 CH 2 C(O)NHCH 2 CH 2 NHC(O)(Fe(η 5 -C 5 H 4 )(η 5 -C 5 H 4 PPh 2 (Pd(η 3 -C 3 H 5 )Cl)))) 2 ] 2 ( 8 - Fe – Pd ) were synthesized. Additionally, seleno-phosphines of 5 - Fe – Se and 9 - Fe – Se , respectively, were prepared by addition of elemental selenium to 5 - Fe or 9 - Fe to estimate their σ- donor properties. The palladium-containing amidoamine supports are catalytically active in the Heck–Mizoroki cross-coupling of iodobenzene with tert -butyl acrylate. The catalytic data are compared to those obtained for the appropriate mononuclear and dinuclear compounds 5 - Fe – Pd and 6 - Fe – Pd . This comparison confirms a positive cooperative effect. The mercury drop test showed that (nano)particles were formed during catalysis, following on heterogeneous carbon–carbon cross-coupling.

The synthesis and reaction chemistry of heteromultimetallic transition metal complexes in which Fc, [(η 6 -C 6 H 5 )Cr(CO) 3 ], [(Ar 3 P)Au], [AuC C-bpy] and [{[Ti](μ-σ,π-C CSiMe 3 ) 2 }Cu] + units (Fc = (η 5 -C 5 H 4 )(η 5 -C 5 H 5 )Fe; [Ti] = (η 5 -C 5 H 4 SiMe 3 ) 2 Ti; bpy = 2,2′-bipyridyl-5-yl) are linked by alkynyl-, benzene- and phosphane- or bipyridyl-based connecting moieties is discussed. In context with this background the preparation of neutral heterotrimetallic 1-(FcC C)-3-[(CO) 3 Cr(η 6 -C 6 H 5 C C)]-5-[(Ph 3 P)AuC C]C 6 H 3 ( 10 ) and ionic heteropentametallic [1-(FcC C)-3-[(CO) 3 Cr(η 6 -C 6 H 5 C C)]-5-[(PPh 2 )AuC C-bpy({[Ti](μ-σ,π-C CSiMe 3 ) 2 }Cu)]C 6 H 3 ](PF 6 ) ( 19 ) from 1-iodo-3,5-dibromobenzene ( 1 ) is reported by applying consecutive reaction methodologies including substitution, complexation and carbon–carbon cross-coupling reactions. The identities of all complexes have been confirmed by elemental analysis and IR, 1 H and 31 P{ 1 H} NMR spectroscopy; heteropentametallic 19 was additionally characterized by ESI-TOF mass-spectrometry.