Synthesis and structure–activity relationships of pyrazolodiazepine derivatives as human P2X7 receptor antagonists

Screening of library compounds has yielded pyrazolodiazepine derivatives with P2X₇ receptor antagonist activity. To explore the structure–activity relationships (SAR) of these pyrazolodiazepines as human P2X₇ receptor antagonists, derivatives were synthesized by substitutions at positions R² and R³ of the pyrazolodiazepine skeleton. Using a 2′(3′)-O-(4-benzoylbenzoyl)ATP (BzATP)-induced fluorescent ethidium uptake assay, the activities of these derivatives were tested in HEK-293 cells stably expressing human P2X₇ receptors. Moreover, the effect of these derivatives was assessed by measuring their effect on IL-1β release induced by BzATP-induced activation of differentiated THP-1 cells. A 2-phenethyl pyrazolodiazepine derivative with a 1-methyl-1H-3-indolyl group at position R² had fivefold greater activity than the derivative with a 5-isoquinolinyl at R². Moreover, a benzyl moiety at R³ had fivefold greater activity than a bicyclic moiety. The stereochemical effect at C-6 showed a preference for the (R)-isomer. Among the series of active derivatives, compound 23b, with a phenethyl group at R¹, a 3-methyl indole at R², and a benzyl at R³, exhibited activity similar to that of the positive control, KN-62, as shown by the inhibitory effects of IL-1β release.     

Synthesis and biological activity of the probable biosynthetic precursors of 241-norbrassinolide

A series of 24¹-norbrassinolide biosynthetic precursors containing 3??-OH, 3-keto, ??²- or 2??,3??-epoxy functional groups less polar than 2??,3??-diol group in A-ring, and (22R,23R)-diol group in the side chain, was synthesized. Their biological activity as the proliferation regulators in MCF-7 human breast cancer and LNCaP human prostate adenocarcinoma cells was studied. It was shown that the majority of the derivatives obtained effectively suppress cell proliferation. The dependence of proliferation on the concentration of the studied compounds was found in LNCaP human prostate adenocarcinoma cells (IC₅₀ = 13?C28 ??M at 72 h of incubation in a medium containing 10% FBS, and suppression of DNA biosynthesis). Some compounds stimulated apoptosis (23?C33%), blocked the cell cycle in S- and G2/M-phases, and induced a partial detachment of cells during a prolonged incubation.     

Discovery of novel pyrrolo[2,3-b]pyridine derivatives bearing 4-oxoquinoline moiety as potential antitumor inhibitor

A series of pyrrolo[2,3-b]pyridine derivatives bearing 4-oxoquinoline moiety were designed, synthesized and evaluated for the anti-proliferative on three cancer cell lines (A549, HepG2 and MCF-7) in vitro. Most of the compounds showed moderate to high potency. Some excellent compounds were tested for the inhibitory activity of c-Met kinase. Compound 34 (c-Met IC₅₀ = 17 nM) was investigated the selectivity against Flt-3, c-Kit, VEGFR-2, ALK, PDGFR-β and RON. Structure-activity relationship studies indicated that hydrogen, fluorine atom, and mono-electron-withdrawing groups (mono-EWGs, such as R² = F) on R, R¹ and R², respectively, were beneficial for the anti-proliferative activities of the target compounds. Besides, we have took further study on the combined mode between compound 34 and c-Met kinase through molecular docking.     

Discovery of novel 2-substituted-4-phenoxypyridine derivatives as potential antitumor agents

A series of 2-substituted-4-phenoxypyridine derivatives were designed, synthesized, and evaluated for their antiproliferative activity against 4 cancer cell lines (A549, HT-29, H460, and U87MG) in vitro. Most compounds showed moderate to excellent potency. Nine tyrosine kinases (c-Met, Flt-3, ALK, VEGFR-2, VEGFR-3, PDGFR-α, PDGFR-β, c-Kit, and EGFR) were used to evaluate the inhibitory activities with the most promising analogue 39, which showed the Flt-3/c-Met IC₅₀ values of 2.18/2.61?nM. Structure-activity relationship studies indicated that n-Pr served as R¹ group showed a higher preference, and stronger mono-EWGs on the phenyl ring (such as R²?=?4-F) was benefited to the potency.     

Synthesis of matrinic amide derivatives containing 1,3,4-thiadiazole scaffold as insecticidal/acaricidal agents

In continuation of our program aimed at the development of natural product-based pesticidal agents, a series of matrinic amide derivatives containing 1,3,4-thiadiazole scaffold were prepared, and their insecticidal and acaricidal activities were evaluated against Mythimna separata and Tetranychus cinnabarinus. Some compounds exhibited potent insecticidal and acaricidal activities. It suggested that R¹ as a nitro group and R² as a fluorine atom, were important for the insecticidal activity; R¹ as the electron-donating groups and R² as the methyl group, were necessary for the acaricidal activity.     

Synthesis and antiproliferative evaluation of piperazine-1-carbothiohydrazide derivatives of indolin-2-one

By varying the substituents (R¹) at the indolin-2-one scaffold, a series of indolin-2-one derivatives bearing 4-phenylpiperazine-1-carbothiohydrazide moiety at the C3-position were synthesized and evaluated for their antiproliferative activity against three human cancer cell lines. We further selected the 5-chloroindolin-2-one moiety for the extension to another series of compounds by varying the substituents (R²) at the phenyl group connected with the piperazine ring. Among all the compounds synthesized, 6d and 6l were most potent with IC₅₀ values of 3.59 and 5.58 μM, respectively against A549 lung cancer cells, while 5f and 6l possessed IC₅₀ values of 3.49 and 4.57 μM, respectively against HCT-116 colon cancer cells which were comparable to that of Sunitinib, an indolin-2-one derivative in cancer therapy.     

Synthesis and acetylcholinesterase inhibitory activities of tabersonine derivatives

Tabersonine, the main alkaloid in Voacanga seeds, was used as a lead compound to semi-synthesize tabersonine derivatives. In total, 13 compounds, containing 10 novel tabersonine derivatives, were synthesized by introducing substituent groups R₁–R₅. The acetylcholinesterase (AChE) inhibitory activities of tabersnonine derivatives were evaluated using Ellman’s method. Among them, compound (7) showed the highest AChE inhibitory activity with the IC₅₀ value was 5.32 μM. The substituent groups R₁–R₅ showed different influences on the AChE inhibitory activities of tabersonine derivatives. The AChE inhibitory activities of tabersonine derivatives increased with the introduction of group R₁ and/or combined groups R₃, R₄, while decreased with the introduction of group R₅. And the group R₂ showed no significant influence on the AChE inhibitory activities of tabersonine derivatives.     

Synthesis and structure–activity relationships of novel,substituted 5,6-dihydrodibenzo[a,g]quinolizinium P2X7 antagonists

Iminium quaternary protoberberine alkaloids (QPA) have been found to be novel P2X₇ antagonists. To assess their structure–activity relationships, these compounds were modified at their R¹ and R² groups and assayed for their ability to inhibit the 2′(3′)-O-(4-benzoylbenzoyl)-ATP (BzATP)-induced uptake of fluorescent ethidium by HEK-293 cells stably expressing the human P2X₇ receptor, and their ability to inhibit BzATP-induced IL-1β release by differentiated THP-1 cells. Compounds 15a and 15d, with alkyl groups at the R¹ position, and especially compound 19h, with the 2-NO₂-4,5-dimethoxy-benzyl group at the R² position, had potent inhibitory efficacy as P2X₇ antagonists.     

Design,synthesis and evaluation against Mycobacterium tuberculosis of azole piperazine derivatives as dicyclotyrosine (cYY) mimics

Three series of azole piperazine derivatives that mimic dicyclotyrosine (cYY), the natural substrate of the essential Mycobacterium tuberculosis cytochrome P450 CYP121A1, were prepared and evaluated for binding affinity and inhibitory activity (MIC) against M. tuberculosis. Series A replaces one phenol group of cYY with a C3-imidazole moiety, series B includes a keto group on the hydrocarbon chain preceding the series A imidazole, whilst series C explores replacing the keto group of the piperidone ring of cYY with a CH₂-imidazole or CH₂-triazole moiety to enhance binding interaction with the heme of CYP121A1. The series displayed moderate to weak type II binding affinity for CYP121A1, with the exception of series B 10a, which displayed mixed type I binding. Of the three series, series C imidazole derivatives showed the best, although modest, inhibitory activity against M. tuberculosis (17d MIC?=?12.5?μg/mL, 17a 50?μg/mL). Crystal structures were determined for CYP121A1 bound to series A compounds 6a and 6b that show the imidazole groups positioned directly above the haem iron with binding between the haem iron and imidazole nitrogen of both compounds at a distance of 2.2?Å. A model generated from a 1.5?Å crystal structure of CYP121A1 in complex with compound 10a showed different binding modes in agreement with the heterogeneous binding observed. Although the crystal structures of 6a and 6b would indicate binding with CYP121A1, the binding assays themselves did not allow confirmation of CYP121A1 as the target.     

Donor-substituted allenylidene(carbonyl)(XR3)chromium complexes (X=P, As, Sb) - synthesis and properties

Photolysis of the allenylidene pentacarbonyl chromium complexes [(CO)₅CrCCC(R¹)R²] (R¹=NMe₂, NPh₂; R²=NMe₂, OMe, Ph) in THF in the presence of equimolar amounts of XR₃ (XR₃=various phosphanes, P(OMe)₃, AsPh₃, SbPh₃) affords cis-allenylidene tetracarbonyl XR₃ complexes, cis-[(CO)₄(XR₃)CrCCC(R¹)R²]. When in the photolysis of [(CO)₅CrCCC(NMe₂)Ph], the phosphanes PR₃ (R=C₆H₄F-p, C₆H₄Cl-p, OMe) are used in excess (three equivalents) two carbonyl ligands are displaced and the mer-tricarbonyl complexes mer-[(CO)₃(PR₃)₂CrCCC(NMe₂)Ph] are formed both PR₃ ligands being mutually trans. The structure of the new complexes is established by IR, NMR, and UV-Vis spectroscopy, that of cis-[(CO)₄(PPh₃)CrCCC(NMe₂)Ph] additionally by an X-ray structural analysis. As indicated by the spectroscopic data of the compounds, these complexes are best described as hybrids of allenylidene and zwitterionic alkynyl complexes with delocalization of the electron pair at nitrogen bonded to the C_γ atom of the allenylidene ligand towards the metal center. The relative contribution of the allenylidene and zwitterionic alkynyl resonance forms is influenced by XR₃. Increasing the donor properties of XR₃ favors the allenylidene resonance form.     

An active site-directed, irreversible inactivation of yeast hexokinase by (R,S)2,3-epoxypropyl beta-D-glucopyranoside

(1) Only (R,S)2′,3′-epoxypropyl β-d-glucopyranoside of the complete series of mono (R,S)2′.3′-epoxypropyl ethers and glycosides of d-glucopyranose significantly inactivated yeast hexokinase.(2) (R,S)2′,3′-Epoxypropyl β-d-glucopyranoside inactivates yeast hexokinase in the absence of MgATP^2?, The rate of inactivation is unaffected by MgATP^2?.(3) The rate of inactivation of hexokinase with (R,S)2′,3′-epoxypropyl β-d-ilucopyranoside was much greater when hexokinase was present in a monomeric form than when it was present in a dimeric form.(4) (R,S)2′,3′-Epoxypropyl β-d-glucopyranoside has a high K_t (0.38 M) and at a saturating concentrarion, the first order rate constant for the inactivation of monomeric hexokinase is 8.3 · 10^?4 sec.(5) d-Glucose protects against this inactivation and this was used to derive a dissocistion constant of 0.21 mM for d-glucose in the absence of MgATP^2?.(6) The alkylation of yeast hexokinase by (R,S)2′,3′-epoxypropyl β-d-gluco-pyranoside was not specific to the active site. When the concentration of (R,S)2′,3′-epoxypropyl β-d-glucopyranoside was 50 mM two thiol groups outside the active site were also alkylated.(7) The reaction between 5,5′-dithiobis-(2-nitrobenzoic acid) (DTNB) and yeast hexokinase was examined in detail. Two thiol groups per monomer (mol. wt. 50000) reacted with a second order rate constant of 27 1 mole^?1 sec^?1. A third thiol group reacted more slowly with a second-order rate constant of 1.6 1 mole^?1 sec^?1 and a fourth thiol group reacted very slowly with inactivation of the enzyme. Tue second-order rate constant in this case was 0.1 1 mole^?1 sec^?1.     

Highly efficacious factor Xa inhibitors containing α-substituted phenylcycloalkyl P4 moieties

We previously disclosed a series of highly potent FXa inhibitors bearing α-substituted (CH₂NR¹R²) phenylcyclopropyl P4 moieties in the pyrazolodihydropyridone core system. Herein, we describe our continuous SAR efforts in this series. Effects of the C-3 substitution of the pyrazolodihydropyridone core and the α-substitution (R group) of the cyclopropyl ring on FXa binding affinity (FXa K_i), human plasma anticoagulant activity (PT EC_2×) and permeability are discussed. A set of compounds obtained from optimization of the R group and the C-3 substituent were orally bioavailable in dogs. Furthermore, representative compounds were highly efficacious in the rabbit arterio-venous shunt thrombosis model (EC₅₀s = 29–81 nM).     

Tetrazole-based deoxyamodiaquines: Synthesis,ADME/PK profiling and pharmacological evaluation as potential antimalarial agents

A series of new deoxyamodiaquine-based compounds was synthesized via the modified TMSN₃-Ugi multi-component reaction and evaluated in vitro for antiplasmodial activity. The most potent compounds, 6b, 6c and 6j, showed IC₅₀ values in the range of 6–77 nM against chloroquine-resistant K1- and W2-strains of Plasmodium falciparum. In vitro ADME characterization of frontrunner compounds 6b and 6c indicates that these two compounds are rapidly metabolized and have a high clearance rate in human and rat liver microsomes. This result correlated well with an in vivo pharmacokinetics study, which showed low bioavailability of 6c in rats. Tentative metabolite identification was determined by LC–MS and suggested metabolic lability of groups attached to the tertiary nitrogen. Preliminary studies on 6b and 6c suggested strong inhibitory activity against the major CYP450 enzymes. In silico docking studies were used to rationalize strong inhibition of CYP3A4 by 6c. Full characterization and biological evaluation of the metabolites is currently underway in our laboratories.     

Synthesis, β-haematin inhibition,and in vitro antimalarial testing of isocryptolepine analogues: SAR study of indolo[3,2-c]quinolines with various substituents at C2, C6, and N11

A series of indolo[3,2-c]quinolines were synthesized by modifying the side chains of the ω-aminoalkylamines at the C6 position and introducing substituents at the C2 position, such as F, Cl, Br, Me, MeO and NO₂, and a methyl group at the N11 position for an SAR study. The in vitro antiplasmodial activities of the derivative agents against two different strains (CQS: NF54 and CQR: K1) and the cytotoxic activity against normal L6 cells were evaluated. The test results showed that compounds 6k and 6l containing the branched methyl groups of 3-aminopropylamino at C6 with a Cl atom at C2 exhibited a very low cytotoxicity with IC₅₀ values above 4000 nM, high antimalarial activities with IC₅₀ values of about 11 nM for CQS (NF54), IC₅₀ values of about 17 nM for CQR (K1), and RI resistance indices of 1.6. Furthermore, the compounds were tested for β-haematic inhibition, and QSAR revealed an interesting linear correlation between the biological activity of CQS (NF54) and three contributing factors, namely solubility, hydrophilic surface area, and β-haematin inhibition for this series. In vivo testing of 6l showed a reduction in parasitaemia on day 4 with an activity of 38%.     

Effects of physical and chemical treatments on chloroplast manganese. NMR and ESR studies

Measurements were made of the water proton relaxation rate (T^?1₂ = R₂), electron spin resonance (ESR) six-line signal of ‘free’ Mn²⁺, and O₂-evolution activity in thylakoid membranes from pea leaves. The main results are: (1) Aging of thylakoids at 35°C causes a parallel decrease in O₂-evolution activity, in R₂ and in the content of bound Mn, suggesting that R₂ may be related to the loosely bound Mn involved in O₂ evolution. (2) Treatment of thylakoids with tetraphenylboron (TPB) at [TPB] > 2 mM produces a 2-fold increase in R₂, without release of Mn²⁺. The titration curve exhibits three sharp end points. The first end point occurs at a $\text{[}\text{TPB}\text{]}\text{[}\text{chlorophyll}\text{]}$ of 1.25, at which the O₂ evolution is completely inhibited. (3) Treatment of thylakoids with NH₂OH also increases R₂ by nearly 2-fold, either by the reduction of the higher oxidation states of Mn to Mn²⁺ and / or by exposing the Mn to solvent protons. Also, progressive release of bound Mn occurs at [NH₂OH] ≥ 1 mM as shown by an increase increase in the Mn²⁺ ESR signal and a decrease in R₂. (4) Addition of H₂O₂ (0.1–1.0%) to thylakoids causes an enhancement of R₂ similar to that by NH₂OH, but without the release of Mn²⁺. (5) Heat treatment of thylakoids at 40–50°C releases Mn²⁺ and increases R₂. Conversely, pH values of 7 to 4 release Mn²⁺ without changing R₂ while pH values of 7–9 increase R₂ without releasing Mn²⁺. Thus, both high and low pH values as well as the heat treatment cause structural changes enhancing the relaxivity of the bound Mn or of other paramagnetic species.     

Evaluation of andrographolide-based analogs derived from Andrographis paniculata against Mythimna separata Walker and Tetranychus cinnabarinus Boisduval

To discover new natural-product-based pesticides, we structurally modified andrographolide, a labdane diterpenoid isolated from Andrographis paniculata, and stereoselectively prepared a series of 12α-(substituted)benzylamino-14-deoxyandrographolide derivatives (I–V). Three-dimensional structures of compounds 3c, 3d, IIIa and IIIb were further determined by single-crystal X-ray diffraction. Compounds IIa (R¹ = n-C₃H₇, R² = PhCH₂) exhibited more promising insecticidal activity against Mythimna separata than toosendanin. Compounds 3a (R¹ = H), Ib (R¹ = H, R² = 4-ClPhCH₂), and IVa (R¹ = 4-ClPh, R² = PhCH₂) showed potent acaricidal activity against Tetranychus cinnabarinus.     

Synthesis of dimethylcobalt(III) complexes containing trimethylphosphine and 2-formyl-phenolato- or 2-formyl-enolato(O:O) ligands

Substituted salicylaldehydes [C₆HR¹R²R³(CHO)(OH)] react with CoMe₃(PMe₃)₃ to afford 6-coordinate (cis-dimethyl)(2-formyl-phenolato)trans-bis(trimethylphosphine)cobalt(III) compounds Co[C₆HR¹R²R³(CHO)(O)Me₂](PMe₃)₂ (1: R¹ = H; R² = Me; R³ = tert-Bu; 2: R¹, R² = C₆H₄; R³ = H). Accordingly, substituted enolated malonic dialdehydes (CHO-CR⁴CR⁵-OH) react with CoMe₃(PMe₃)₃ to afford 6-coordinate (cis-dimethyl)(2-formyl-enolato)trans-bis(trimethylphosphine)cobalt(III) compounds Co[(CHO-CR⁴CR⁵-O)(Me)₂](PMe₃)₂ (3: R⁴, R⁵ = (CH₂)₂C₆H₄; 4: R⁴ = R⁵ = C₆H₅). In the molecular structure of 4, the cobalt atom is centred in an octahedral coordination geometry brought about by a six-membered chelate ring (O:O-ligand), cis-dimethyl and trans-trimethylphosphine groups. A reaction mechanism is suggested.     

A series of meso-tris(N-methyl-pyridiniumyl)-(4-alkylamidophenyl) porphyrins: Synthesis,interaction with DNA and antibacterial activity

A series of meso-5,10,15-tris(N-methyl-4-pyridiniumyl)-20-(4-alkylamidophenyl) porphyrins were synthesized by derivatizing the amino group on the phenyl ring with the following hydrophobic groups: –C(O)C₇F₁₅, –C(O)CHCH₂, C(O)CH₃, –C(O)C₇H₁₅, and –C(O)C₁₅H₃₁. The cationic tris-pyridiumyl porphyrin core serves as a DNA binding motif and a photosensitizer to photomodify DNA molecules. The changes of the UV–Vis absorption spectra during the titration of these porphyrins with calf thymus DNA revealed a large bathochromic shift (up to 14 nm) and a hypochromicity (up to 55%) of the porphyrins Soret bands, usually considered as proof of porphyrin intercalation into DNA. Association constants (K) calculated according to the McGhee and von Hippel model, were in the range of 10⁶–10⁷ M⁻¹. An increase in hydrophobicity of the substituents at the 20−meso-position produced higher binding affinity. These porphyrins caused photomodification of the supercoiled plasmid DNA when a green laser beam at 532 nm was applied. Those with higher surface activity acted more efficiently as DNA photomodifiers. The porphyrin with a perfluorinated alkyl chain (–COC₇F₁₅) at the meso-20-position inhibited the growth of gram-positive bacteria (S. aureus, or S. epidermidis). Other porphyrins exhibited moderate activity against both gram-negative and gram-positive organisms.     

29Si and 13C chemical shifts and coupling constants of tris(phenyldimethylsilyl)methyl silicon compounds

Silicon-29 (δ ²⁹Si) NMR chemical shifts are reported for the first time for a number of tris(phenyldimethylsilyl)methyl silicon compounds (disilylated derivatives), (PhMe₂Si^A)₃C_αL, where LSi^BR₁R₂R₃, where R varies widely in electronegativity. δ ²⁹Si^B for these series exhibited to some extent good correlations with the electronegativities of the groups bonded to silicon (particularly, δ ²⁹Si^BMe₂X, X H, OH, OCH₃, COCH₃ and Cl). Substitution with electronegative atoms shifts the chemical shift of silicon to high field.The ¹³C NMR spectra of these compounds have been recorded and assigned. The chemical shifts of the α-carbon (C_α) resonances are shown to depend on the type of substituent on the silicon-B, thus ¹³C_α exhibit downfield shifts when X=oxygen ligand. The ¹³C phenyl resonances have been measured and show the same order of o, m and p signals, viz. δ ortho (downfield)>δ para>δ meta.The variation of ²⁹Si-¹H coupling constants with the electronegativity of X was studied.     

Synthesis of heterodinuclear FeRu(CO)6(R-DAB(6e))(R-DABRNC(H)C(H)NR) Part XV. Comparison of the reactivities of heterodinuclear FeRu(CO)6(R-DAB(6e)) and homodinuclear analogues M2(CO)6(R-DAB(6e)) (M = Fe,Ru). Single-crystal x-ray structures of FeRu(CO)6(i-Pr-DAB(6e)) and FeRu(CO)5(i-Pr-DAB(4e))(C3H4)

The reactions of Fe(CO)₃(R-DAB; R¹, H(4e)) (1a: R = i-Pr, R¹ = H; 1b: R = t-Bu, R¹ = H; 1c: R = c-Hex, R¹ = H; 1e: R = p-Tol, R¹ = H; 1f: R = i-Pr, R¹ = Me) with Ru₃(CO)₁₂ and of Ru(CO)₃(R-DAB; R¹, H(4e)) (2a: R = i-Pr, R¹ = H; 2d: R = CH(i-Pr)₂, R¹ = H) with Fe₂(CO)₉ in refluxing heptane both afforded FeRu(CO)₆(R-DAB; R¹, H(6e)) (3) in yields between 50 and 65%.The coordination mode of the ligand has been studied by a single crystal X-ray structure determination of FeRu(CO)₆(i-Pr-DAB(6e)) (3a). Crystals of 3a are monoclinic, space group P2₁/a, with four molecules in a unit cell of dimensions: a = 22.436(3), b = 8.136(3), c = 10.266(1) Å and β = 99.57(1)°. The structure was refined to R = 0.049 and R_w = 0.052 using 3045 reflections above the 2.5σ(I) level. The molecule contains an FeRu bond of 2.6602(9) Å, three terminally bonded carbonyls to Fe, three terminally bonded carbonyls to Ru and bridging 6e donating i-Pr-DAB ligand. The i-Pr-DAB ligand is coordinated to Ru via N(1) and N(2) occupying an apical and equatorial site respectively (RuN(1) = 2.138(4) RuN(2) = 2.102(3) Å). The C(2)N(2) moiety of the ligand is η²-coordinated to Fe with C(2) in an apical and N(2) in an equatorial site (FeC(2) = 2.070(5) and FeN(2) = 1.942(3) Å).The ¹H and ¹³C NMR data indicate that in all FeRu(CO)₆(R-DAB(6e)) complexes (3a to 3f) exclusively η²-CN coordination to the Fe atom and not to the Ru atom is present irrespective of whether 3 was prepared by reaction of Fe(CO)₃(R-DAB(4e)) (1) with Ru₃(CO)₁₂ or by reaction of Ru(CO)₃(R-DAB(4e)) (2) with Fe₂(CO)₉. In the case of FeRu(CO)₆(i-Pr-DAB; Me, H(6e)) (3f) the NMR data show that only the complex with the C(Me)N moiety of the ligand σ-N coordinated to the Ru atom and the C(H)N moiety η²-coordinated to the Fe atom was formed. Variable temperature NMR experiments up to 140 °C showed that the α-diimine ligand in 3a is stereochemically rigid bonded.FeRu(CO)₆(R-DAB(6e)) (3a and 3e) reacted with allene to give FeRu(CO)₅(R-DAB(4e))(C₃H₄) (4a and 4e). A single crystal X-ray structure determination of FeRu(CO)₅(i-Pr-DAB(4e))(C₃H₄) (4a) was performed. Crystals of 4a are triclinic, space group P1, with two molecules in a unit cell of dimensions: a = 9.7882(7), b = 12.2609(9), c = 8.3343(7) Å, α = 99.77(1)°, β = 91.47(1)° and γ = 86.00(1)°. The structure was refined to R = 0.028 and R_w = 0.043 using 4598 reflections above the 2σ(I) level. The molecule contains an FeRu bond of 2.7405(7) Å and three terminally bonded carbonyls to iron. Two carbonyls are terminally bonded to the Ru atom together with a chelating 4e donating i-Pr-DAB ligand [RuN = 2.110(1) (mean)]. The allene ligand is coordinated in an η³-allylic fashion to the Fe atom while the central carbon of the allene moiety is σ-bonded to the Ru atom (FeC(14) = 2.166(3), FeC(15) = 1.970(2), FeC(16) = 2.127(3) and RuC(15) = 2.075(2) Å). The ¹H and ¹³C NMR data show that in solution the coordination modes of the R-DAB and the allene ligands are the same as in the solid state.Thermolysis reactions of 3a with R-DAB or carbodiimides gave decomposition and did not afford C(imine)C(reactant) coupling products. Thermolysis reactions of 3a with M₃(CO)₁₂ (M = Ru, Os) and Me₃NO gave decomposition. When the reaction of 3a with Me₃NO was performed in the presence of dimethylacetylenedicarboxylate (DMADC) the known complex FeRu(CO)₄(i-Pr-DAB(8e))(DMADC) (5a) was formed in low yield. In 5a the R-DAB ligand is in the 8e coordination mode with both the imine bonds η²-coordinated to iron. The acetylene ligand is coordinated in a bridging fashion, parallel with the FeRu bond.