Macrocycles, adducts and monomeric boron compounds derived from 2,6-dimethanolpyridine and arylboronic acids

The reaction of 2,6-dimethanolpyridine with arylboronic acids at room temperature led to the formation of tetrameric compounds 1a-1e in good yields. Since the tetrameric derivatives were insoluble in common organic solvents, their characterization was based on IR, mass spectrometry, as well as ¹³C and ¹¹B NMR, in the solid state. Macrocyclic compounds 1a-1e can be hydrolyzed upon heating in DMSO to give adducts 2a-2e, which are only held by a coordination bond between the nitrogen and boron atoms, as demonstrated by ¹H, ¹³C and ¹¹B NMR, in solution. Moreover, the presence of an additional carbon atom in the aliphatic chain of the ligand, as in the case of 2,6(β-diethanolamine)pyridine, leads exclusively to the formation of the monomeric specie 4, as established by X-ray diffraction analysis.     

Coordination compounds of Cd(II) with several bidentate-NN′ and tridentate-NN′N nitrogen donor ligands. Cd NMR studies of monomeric compounds containing nitrogen donor atoms

Reaction of CdCl₂ with N-alkylaminopyrazole ligands 1-[(2-ethylamino)ethyl]-3,5-dimethylpyrazole (deae), 1-[(2-(tert-butylamino)ethyl)]-3,5-dimethylpyrazole (deat), bis-[(3,5-dimethylpyrazolyl)methyl]ethylamine (bdmae), and bis-[(3,5-dimethylpyrazolyl)ethyl]ethylamine (ddae) in absolute ethanol yields [CdCl₂(NN′)] (NN′ = deae (1), deat (2)), [CdCl₂(bdmae)] (3), and [CdCl(ddae)]₂[CdCl₄] (4). The Cd(II) complexes have been characterised by elemental analyses, conductivity measurements, IR, ¹H, ¹³C{¹H} and ¹¹³Cd NMR spectroscopies, and X-ray diffraction methods. ¹H and ¹¹³Cd NMR experiments at variable temperature for 3 and 4 show that dynamic processes are taking place in solution. We report the measurements of ¹¹³Cd NMR chemical shift data for complexes 1-4 in solution. X-ray crystal structures for complexes 2 and 3 have been determined. The Cd(II) is coordinated to the deat ligand, in 2, by one nitrogen atom of the pyrazolyl group and one nitrogen atom of the amine. It finishes a tetrahedral geometry with two chlorine atoms. The bdmae ligand is linked to Cd(II), in 3, by two nitrogens atoms of the pyrazolyl groups and one amine nitrogen, along with two chlorine atoms, in a distorted trigonal bipyramidal geometry.     

Synthesis and spectroscopic and X-ray structural characterisation of some para-substituted triaryltin(pentacarbonyl)manganese(I) complexes

A series of para-substituted triaryltin(pentacarbonyl)manganese(I) compounds [(p-XC₆H₄)₃SnMn(CO)₅: II, X=CH₃; III, X=CH₃O; IV, X=CH₃S; V, X=F; VI, X=Cl; VII, X=CH₃S(O₂)] is reported for comparison with the known phenyl analogue I. IR data [ν(CO)] as well as complete ¹¹⁹Sn/⁵⁵Mn/¹³C solution NMR results are given for I-VII. Chemical shifts, ¹¹⁹Sn versus ⁵⁵Mn, except I, correlate well, but have differing single parameter (SP) correlations, ¹¹⁹Sn versus σ_I and ⁵⁵Mn versus σ°_p. These results are compared with previous SP studies of the ¹¹⁹Sn solution NMR spectra of the series, (p-XC₆H₄)₄Sn and (p-XC₆H₄)₃SnY (Y=Cl, Br, I). Full crystal structures are reported for compounds II-VI. All are similar to that of I, with the Mn(CO)₅ moiety being a distorted tetragonal pyramid, and having a quasi-mirror plane through the central C₄MnSnC₃ skeleton. The Ar₃Sn are distorted trigonal propellers with ring torsion angles in the range 30-80°, the exception being IV with one torsion angle of 22°.     

Ecdysteroids from Polypodium vulgare L

Three new compounds (3, 7, and 11) together with eight known phytoecdysteroids (1, 2, 4-6, and 8-10) were isolated from the rhizomes of common polypody, Polypodium vulgare L. The structures of compounds were elucidated by spectroscopic methods including 1D and 2D NMR measurements. The ¹H and ¹³C NMR assignments of compounds 1, 6, 9 and 10 are included.     

Sargachromanols as inhibitors of Na+/K+ ATPase and isocitrate lyase

Sargachromanols A-P (1-16), 16 meroterpenoids of the chromene class isolated from the brown alga Sargassum siliquastrum, were evaluated for their inhibitory activities toward Na⁺/K⁺ ATPase from porcine cerebral cortex and isocitrate lyase (ICL) from Candida albicans. These studies led to the identification of compounds 4, 6, 8, and 12 as potent Na⁺/K⁺ ATPase inhibitors. Compounds 12, 13, and 16 exhibited moderate ICL inhibitory activity. Compound 12 also showed weak antibacterial activity. The preliminary structure-activity relationship of these compounds is described to elucidate the essential structural requirements.     

Synthesis, characterisation and solution behaviour of fluoroalkyl phosphoryl complexes of tin tetrachloride

The synthesis, characterisation and solution behaviour of a series of octahedral complexes SnCl₄·2L (L = R₂NP(O)(OCH₂CF₃)₂; R = Me (1); Et (2) or L = P(O)(OCH₂R_f)₃; R_f = CF₃ (3); C₂F₅ (4)) are described. Complexes 1-4 were prepared from SnCl₄ and 2 equiv. of the ligand, L, in anhydrous CH₂Cl₂ solution. The adducts have been characterised by multinuclear (¹H, ³¹P and ¹¹⁹Sn) NMR, IR spectroscopy and elemental analysis. In dichloromethane solution, the NMR data showed the presence of a mixture of cis and trans isomers for 1 and 2 and only the cis isomer for 3 and 4. The difference could be interpreted in terms of the electronic effects of the substituents on the phosphorus atom of the ligand. In addition, the solution structure of the complexes studied by variable temperature ³¹P-{¹H} and ¹H NMR in the presence of excess ligand indicated that the ligand exchange on the cis isomer dominates the chemistry. The metal-ligand exchange barriers were estimated to be 13.38 and 11.39 kcal/mol for 1 and 3, respectively. The results are discussed and compared with those previously reported for the related hexamethylphosphoramide adduct, SnCl₄·2HMPA.     

Synthesis, thermal and photophysical properties of phenoxy-substituted dendrimeric cyclic phosphazenes

In the present study, we describe the synthesis of a hydroxyl substituted bridged phenoxycyclotriphosphazene (5), [N₃P₃(OPh)₅OPhO(OPh)₅N₃P₃OPhOH], as a side group and its use for preparation of dendrimeric cyclic phosphazenes. For this purposes, compound 5 is synthesised in five steps from the reactions of cyclotriphosphazene with phenol derivatives. The dendrimeric compounds 6 and 7 have been prepared by the reactions of compound 5 with hexachlorocyclotriphosphazene, N₃P₃Cl₆, or octachlorocyclotetraphosphazene, N₄P₄Cl₈, respectively. Newly synthesized compounds have been fully characterized by elemental analysis, MALDI-TOF mass spectrometry, FT-IR, ¹H, ¹³C and ³¹P NMR spectroscopy. The thermal stability and fluorescence spectral properties of dendrimeric compounds 6 and 7 are investigated and compared with that of the previously reported cyclic compounds (I-II). Fluorescence quantum yields and lifetimes of dendrimeric compounds and their quenching behaviour by 1,4-benzoquinone are studied in dichloromethane.     

The investigation of structural and thermosensitive properties of new phosphazene derivative bearing glycol and aminoalcohol

Three isomers (nongeminal cis-2,4,6 (2); nongeminal trans-2,4,6 (3); geminal 2,2,4 (4)) were isolated from the reaction of hexachlorocyclotriphosphazatriene (trimer) (1) with diethylene glycol monobutyl ether (DEGBE). The substitution reactions of cis-tris isomer (2) with 3-amino-1-propanol were investigated under different solutions conditions to provide amphiphilic phosphazene (5). All of compounds were characterized by using elemental analysis, ³¹P NMR and mass spectroscopies. Thermosensitive properties of compound 5 were studied. The compound 5 is soluble in both water and organic media. This indicates that compound 5 is an amphiphilic molecule. Concentration-dependent LCST (Lower Critical Solution Temperature) behavior of 5 was measured in water. Compound 5 exhibited a reversible and thermosensitive phase transition in aqueous medium, from soluble to insoluble states. Compound 5 showed LCST at 37 °C (for 7 wt.% concentration) which is near to body temperature.     

Synthesis and characterisation of new molybdenum - oxo complexes containing diphenylphosphinylacetic acid and 2-(tert-butylsulphoxide)phenyldiphenylphosphine oxide as bidentate ligands

Reaction of the ligands diphenylphosphinylacetic acid Ph₂P(O)CH₂COOH (1) and 2-(tert-butylthio)phenyldiphenylphosphine oxide Ph₂P(O)C₆H₄^tBuS (2) with “MoO₂Cl₂”, resulted in two complexes MoO₂Cl₂Ph₂P(O)CH₂COOH (3) and MoO₂Cl₂Ph₂P(O)C₆H₄^tBuS(O) (4). Complexes 3 and 4 were isolated and analysed by ¹H NMR, ³¹P NMR and X-ray crystallography. Complex 3 crystallised with a molecule of the free ligand in a 1:1 ratio (3·1) and complex 4 crystallised with molecules of the solvent CH₂Cl₂ within the unit cell in a 2:1 ratio (4·0.5CH₂Cl₂). Tetrameric arrangements comprised of hydrogen bonds were observed in complexes 1 and 3. Complex 4 exhibited a seven-membered ring structure owing to the oxidation of the sulphide in 2 to sulphoxide and coordination of this ligand via the oxygen atoms to the molybdenum atom.     

NMR-based molecular ruler for determining the depth of intercalants within the lipid bilayer Part I. Discovering the guidelines

The development of “molecular rulers” would allow one to quantitatively locate intercalants within the liposomal bilayer. To this end, we have attempted to correlate the ¹³C NMR chemical shift of a polarizable “reporter” carbon (e.g., carbonyl) of the intercalant—with the E_T(30) polarity it experiences, and with its Angstrom distance from the interface. This requires families of molecules with the same two “reporter carbons” separated by a fixed distance, residing at various depths/polarities within the bilayer. The families studied included 4,4-dialkylcyclohexa-2,5-dienones 1, benzenediacetic esters 15, benzenedipropionic esters 17, 4-alkoxybenzaldehydes 19 and methyl 4-alkoxybenzoates 22. These compounds possessed the following characteristics: (1) a planar backbone; (2) polar/hydrophilic “head” groups; (3) modular hydrophobic tails; (4) large changes in the ¹³C NMR chemical shift (Δδ) of the reporter atoms with solvent polarity. These studies revealed a fifth requirement, namely: (5) the reporter carbons must not be strongly conjugated, lest it reflect the charge build-up at another site within the conjugated system.     

11C]sorafenib: radiosynthesis and preliminary PET study of brain uptake in P-gp/Bcrp knockout mice

Sorafenib (Nexavar, BAY43-9006, 1) is a second-generation, orally active multikinase inhibitor that is approved for the treatment of some cancers in patients. In this Letter, we developed [¹¹C]1 as a novel positron emission tomography (PET) probe, and evaluated the influence of ABC transporters-mediated efflux on brain uptake using PET with [¹¹C]1 in P-glycoprotein (P-gp)/breast cancer resistance protein (Bcrp) knockout mice versus wild-type mice. [¹¹C]1 was synthesized by the reaction of hydrochloride of aniline 2 with [¹¹C]phosgene ([¹¹C]COCl₂) to give isocyanate [¹¹C]6, followed by reaction with another aniline 3. Small-animal PET study with [¹¹C]1 indicated that the radioactivity level (AUC_0-60 min, SUV × min) in the brains of P-gp/Bcrp knockout mice was about three times higher than in wild-type mice.     

Sesquiterpene lactones from the endemic Cape Verdean Artemisia gorgonum

Leaves and flowers of Artemisia gorgonum (Asteraceae) collected in Fogo, Cape Verde islands, were phytochemically investigated and resulted in isolation and characterization of three guaianolides 1, 2, 5, and a secoguainolide 4, in addition to eight known guaianolides 6-11 and two known germacranolides 12, 13. Structures were elucidated by 1D and 2D NMR experiments. Careful examination of the ¹³C NMR spectrum led to revision of the structure of a previously described guaianolide from 2 to 3. Most compounds exhibited mild antiplasmodial activities, ridentin (13) being the most interesting with an IC₅₀ of 3.8 ± 0.7 μg ml⁻¹ against Plasmodium falciparum FcB1 and weak cytotoxicity in a vero cell line (IC₅₀ 71.0 ± 3.9 μg ml⁻¹).     

Synthesis and crystal structure of a salicylatooxovanadium(V) complex of an aminebis(phenolate) ligand: Kinetic studies on its formation from corresponding alkoxo complexes

Synthesis and single crystal X-ray structures of H₂L¹ and VO(L¹)(HL) [H₂L¹ = N,N-bis(2-hydroxy-3,5-ditertiarybutyl)-N′,N′-dimethylethylendiamine) or simply aminebis(phenol) and H₂L = salicylic acid) are reported here. The complex [VO(L¹)(HL)] is in distorted octahedral geometry under O₄N₂ donor environment where the basal core is defined by O(1), O(3), O(2) and N(5) atoms and two axial coordinates are occupied by O(4), an alkoxo-group and N(1), an imino-nitrogen atom. The electron spray mass spectrometric study on [VO(L¹)(HL)] in MeCN clearly points out the existence of single species in solution. Again, the ⁵¹V NMR of the bulk polycrystalline sample reveals that the complex [VO(L¹)(HL)] mainly exists in three out of four possible isomers. The formation of [VO(L¹)(HL)] from both [VO(L¹)(OMe)] and [VO(L¹)(OEt)] was followed kinetically by reacting with salicylic acid in MeCN. The presence of isosbestic point indicates a clean conversion of the reactants to product.     

Syntheses and characterization of titanium malonato and amino acid complexes: [Ti(cp)2(OOCCH2NMe2)] - The first structurally characterized α-amino acid titanium(III) complex

The reaction of [Ti(cp^∗)₂(BTMSA)] (1) (cp^∗ = η⁵-C₅Me₅, BTMSA = bis(trimethylsilyl)acetylene) with malonic acids ((HOOC)₂CR₂, R = H, Me) and N,N-dimethylglycine resulted in the formation of titanium(IV) dicarboxylato complexes [Ti(cp^∗)₂{(OOC)₂CR₂}] (R = H, 2; R = Me, 3) and an α-amino acid titanium(III) complex [Ti(cp^∗)₂(OOCCH₂NMe₂)] (4). The identities of complexes 2-4 were confirmed by microanalysis, ¹H and ¹³C NMR spectroscopy (2, 3), ESI-MS and CID experiments (2, 3) as well as by ESR and magnetic measurements (μ_eff = 1.81, 298 K) for 4. Single X-ray diffraction analyses of 2 and 4 exhibited monomolecular complexes in which the titanium atom is distorted tetrahedrally coordinated by two η⁵-C₅Me₅ rings and by the chelating bound malonato-κ²O,O′ (2) and N,N-dimethylglycinato-κ²O,O′ ligand (4).     

New organotin complexes with trans(cis)-1,4-cyclohexanedicarboxylic acid: Synthesis, characterization and crystal structures of mononuclears, 2D network polymers and a tetratin macrocycle

A series of new organotin carboxylates have been synthesized by reactions of trans(cis)-1,4-cyclohexanedicarboxylic acid with triorganotin chloride and diorganotin dichloride. All the complexes were characterized by elemental analysis, IR, ¹H NMR, ¹³C NMR, ¹¹⁹Sn NMR spectroscopy; furthermore, complexes 1, 3, 5, 8 and 9 were characterized by X-ray diffraction analyses. The structural analyses show that complex 1 possesses a monomer structure; complex 5 possesses a 1D zigzag chain structure; both the complexes 3 and 8 have 2D network structures and complex 9 has a tetratin 36-membered macrocyclic structure.     

The first iron(III) complexes with cyclin-dependent kinase inhibitors: Magnetic, spectroscopic (IR, ES+ MS, NMR, Fe Mössbauer), theoretical, and biological activity studies

The first Fe^III complexes 1-6 with cyclin-dependent kinase (CDK) inhibitors of the type [Fe(L_n)Cl₃]·nH₂O (n = 0 for 1, 1 for 2, 2 for 3-6; L₁-L₆ = C2- and phenyl-substituted CDK inhibitors derived from 6-benzylamino-9-isopropylpurine), have been synthesized and characterized by elemental analysis, IR, ⁵⁷Fe Mössbauer, ¹H and ¹³C NMR, and ES+ mass spectroscopies, conductivity and magnetic susceptibility measurements, and thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). The study revealed that the compounds are mononuclear, tetrahedral high-spin (S = 5/2) Fe^III complexes with an admixture of an S = 3/2 spin state originating probably from five-coordinated Fe^III ions either connecting with a bidentate coordination mode of the CDK inhibitor ligand or relating to the possibility that one crystal water molecule enters the coordination sphere of the central atom in a portion of molecules of the appropriate complex. Nearly spin-only value of the effective magnetic moment (5.82 μ_eff/μ_B) was determined for compound 1 due to absence of crystal water molecule(s) in the structure of the complex. Based on NMR data and DFT calculations, we assume that the appropriate organic ligand is coordinated to the Fe^III ion through the N7 atom of a purine moiety. The cytotoxicity of the complexes was tested in vitro against selected human cancer cell lines (G-361, HOS, K-562 and MCF-7) along with the ability to inhibit the CDK2/cyclinE kinase. The best cytotoxicity (IC₅₀: 4-23 μM) and inhibition activity (IC₅₀: 0.02-0.09 μM) results have been achieved in the case of complexes 2-4, and complexes 3, 4 and 6, respectively. In addition, the X-ray structure of 2-chloro-6-benzylamino-9-isopropylpurine, i.e. a precursor for the preparation of L₁, L₄ and L₅, is also described.     

Cd(II)-ethylenediamine mono- and bimetallic complexes - Synthesis and characterization by Cd NMR spectroscopy and single crystal X-ray diffraction

Formation of three Cd(II)-ethylenediamine (en) complexes ([Cd(en)_n]²⁺, n = 1-3) in aqueous solution and in DMSO solvent has been established by means of ¹¹³Cd NMR spectroscopy. It is clearly shown that Cd(II)-en complexes form primarily in basic solutions. A correlation between the ¹¹³Cd NMR chemical shifts and the ethylenediamine (en) coordination number has been observed and discussed. Two single crystals with the composition [Cd₂(en)₅](ClO₄)₄ (1) and [Cd(en)₃](ClO₄)₂ (2) were prepared from aqueous solution, and their structures were determined by single crystal X-ray diffraction. Cd(II) ions are coordinated by six atoms in both compounds, 1 and 2: via five N-donor atoms and one O-donor atom forming a bimetallic complex 1, and via six N-donor atoms forming a distorted octahedral monometallic complex 2. Raman spectra of complexes 1 and 2 also provide additional evidence that the cis-form of the bridging en is present in complex 1.     

Synthesis, spectroscopical characterization and the biological activity in vitro of new platinum(II) complexes with imidazo[1,5-a]-1,3,5-triazine derivatives and dimethylsulfoxide

A series of platinum(II) complexes with 6,8-dimethylimidazo[1,5-a]-1,3,5-triazin-4(3H)-one (6,8-DiMe-4-O-IMT) (I) and 6,8-dimethyl-2-thioxo-2,3-dihydroimidazo[1,5-a]-1,3,5-triazin-4(1H)-one (6,8-DiMe-4-O-2-S-IMT) (II) of formula trans-[PtCl₂(dmso)(6,8-DiMe-4-O-IMT)] (1a) and trans-[PtCl₂(dmso)(6,8-DiMe-4-O-2-S-IMT)] (2a) have been prepared and characterized with ¹H, ¹³C, ¹⁵N, ¹⁹⁵Pt NMR and IR. Significant ¹⁵N NMR upfield coordination shifts (81-96 ppm) of N(7) atom indicate this nitrogen atom as a coordination site. The multinuclear NMR and IR spectra indicate the square planar geometry with N(7) bonded heterocycles, S-bonded dimethylsulfoxide and two trans chloride anions. The platinum(II) complexes were tested for their antiproliferative activity in vitro against the cells of four human cell lines: SW707 rectal adenocarcinoma, A549 non-small cell lung carcinoma, T47D breast cancer and HCV29T bladder cancer. The activity of (1a, 2a) was lower than that of cisplatin.     

fac-/mer-[RuCl3(NO)(P-N)] (P-N = [o-(N,N-dimethylamino)phenyl]diphenylphosphine): Synthesis, characterization and DFT calculations

Complex fac-[RuCl₃(NO)(P-N)] (1) was synthesized from the reaction of [RuCl₃(H₂O)₂(NO)] and the P-N ligand, o-[(N,N-dimethylamino)phenyl]diphenylphosphine) in refluxing methanol solution, while complex mer,trans-[RuCl₃(NO)(P-N)] (2) was obtained by photochemical isomerization of (1) in dichloromethane solution. The third possible isomer mer,cis-[RuCl₃(NO)(P-N)] (3) was never observed in direct synthesis as well as in photo- or thermal-isomerization reactions. When refluxing a methanol solution of complex (2) a thermally induced isomerization occurs and complex (1) is regenerated.The complexes were characterized by NMR (³¹P{¹H}, ¹⁵N{¹H} and ¹H), cyclic voltammetry, FTIR, UV-Vis, elemental analysis and X-ray diffraction structure determination. The ³¹P{¹H} NMR revealed the presence of singlet at 35.6 for (1) and 28.3 ppm for (2). The ¹H NMR spectrum for (1) presented two singlets for the methyl hydrogens at 3.81 and 3.13 ppm, while for (2) was observed only one singlet at 3.29 ppm. FTIR Ru-NO stretching in KBr pellets or CH₂Cl₂ solution presented 1866 and 1872 cm⁻¹ for (1) and 1841 and 1860 cm⁻¹ for (2). Electrochemical analysis revealed a irreversible reduction attributed to Ru^II-NO⁺ → Ru^II-NO⁰ at −0.81 V and −0.62 V, for (1) and (2), respectively; the process Ru^II → Ru^III, as expected, is only observed around 2.0 V, for both complexes.Studies were conducted using ¹⁵NO and both complexes were isolated with ¹⁵N-enriched NO. Upon irradiation, the complex fac-[RuCl₃(NO)(P-N)] (1) does not exchange ¹⁴NO by ¹⁵NO, while complex mer,trans-[RuCl₃(NO)(P-N)] (2) does. Complex mer,trans-[RuCl₃(¹⁵NO)(P-N)] (2′) was obtained by direct reaction of mer,trans-[RuCl₃(NO)(P-N)] (2) with ¹⁵NO and the complex fac-[RuCl₃(¹⁵NO)(P-N)] (1′) was obtained by thermal-isomerization of mer,trans-[RuCl₃(¹⁵NO)(P-N)] (2′).DFT calculation on isomer energies, electronic spectra and electronic configuration were done. For complex (1) the HOMO orbital is essentially Ru (46.6%) and Cl (42.5%), for (2) Ru (57.4%) and Cl (39.0%) while LUMO orbital for (1) is based on NO (52.9%) and is less extent on Ru (38.4%), for (2) NO (58.2%) and Ru (31.5%).     

Methylated anthocyanidin glycosides from flowers of Canna indica

Methylated anthocyanin glycosides were isolated from red Canna indica flower and identified as malvidin 3-O-(6-O-acetyl-β-d-glucopyranoside)-5-O-β-d-glucopyranoside (1), malvidin 3,5-O-β-d-diglucopyranoside (2), cyanidin-3-O-(6″-O-α-rhamnopyranosyl-β-glucopyranoside (3), cyanidin-3-O-(6″-O-α-rhamnopyranosyl)-β-galactopyranoside (4), cyanidin-3-O-β-glucopyranoside (5) and cyanidin-O-β-galactopyranoside (6) by HPLC-PDA. Their structures were subsequently determined on the basis of spectroscopic analyses, that is, ¹H NMR, ¹³C NMR, HMQC, HMBC, ESI-MS, and UV-vis. Compounds (1-4) were found to be in major quantity while compounds (5-6) were in minor quantity.