Temperature-dependent racemic compound-conglomerate crystallization of 2,3:6,7-dibenzobicyclo[3.3.1]nona-2,6-diene-4,8-dione

2,3:6,7-dibenzobicyclo[3.3.1]nona-2,6-diene-4,8-dione 1 is a new example of a compound capable of temperature-dependent racemate-conglomerate crystallization: at temperatures below 90°C crystals of the racemic compound (space group P1̄, Z=4) can be obtained, whereas above 100°C a conglomerate of (+)- and (−)-homochiral crystals (space group P2₁2₁2₁, Z=4) forms and therefore it undergoes spontaneous resolution upon crystallization. Enantioselective analytical gas chromatography on a single crystal has been proposed as a simple method for detection of conglomerate formation. The ¹H and ¹³C NMR spectra of 1 are analyzed in detail and the crystal structures of both species (racemic compound and single enantiomer) have been solved by X-ray structural analysis.     

Synthesis, crystal structure and thermal analysis of tetraiodo-4, 4’-bi-1, 2, 4-triazole

Tetraiodo-4,4’-bi-1,2,4-triazole(1)was synthesized from a reaction of iodine monochloride with 4,4’-bi-1,2,4-triazole(2),which was prepared by a transamination reaction between 4-amine-1,2,4-triazole and N,N-dimethylformamide azine dihydrochloride(3)obtained via a Vilsmeier reaction.The title compound was extensively characterized by melting point,elemental analysis,IR,HRMS and single crystal X-ray diffraction.The single crystal X-ray structural analysis reveals that compound 1 exhibits a stable conformation with the two triazole rings being perpendicular to minimize three-dimensional steric hindrance and stacking through aromatic π...π packing interactions between molecules.The thermal analysis from TGA and DSC indicates that compound 1 decomposes at 275.40℃ and 338.35℃,respectively.     

Preparation of a high performance liquid chromatography column based on N-(3,5-dinitrobenzoyl)-aminoundecyl silica for the resolution of liquid crystal mixtures

A bonded silica stationary phase (SP 1) was prepared by connecting N-(3,5-dinitrobenzoyl) aminoundecylsilane to silica gel. The stationary phase was applied in resolving a liquid crystal mixture with a reversed phase high performance liquid chromatography (HPLC) mode and the chromatographic resolution results were compared with those on an octadecylsilane (ODS) column. From the comparison of the resolution results on SP 1 and the ODS column, we found the new stationary phase was better than the ODS column in resolving a liquid crystal mixture and the elution orders of some liquid crystal were changed. The better resolution and the change in the elution orders on the new column might be originated from additional π–π interaction between the π-acidic 3,5-dinitrobenzoyl group of the stationary phase and the π-basic aromatic group of liquid crystals.     

Tumor-homing peptide-based NIR-II probes for targeted spontaneous breast tumor imaging

Fluorescence imaging in the second near-infrared window(NIR-Ⅱ,1000-1700 nm) is a promising modality for real-time imaging of cancer and image-guided surgery with superior in vivo optical properties.So far,very few NIR-Ⅱ fluorophores have been reported for in vivo biomedical imaging of chemically-induced spontaneous breast carcinoma.Herein,a NIR-Ⅱ fluorescent probe CH1055-F3 with the nucleolin-targeted tumor-homing peptide F3 was demonstrated to prefe rentially accumulate in 4 T1 tumors.More importantly,CH1055-F3 exhibited specific NIR-Ⅱ signals with high spatial and temporal resolution,strong tumor uptake,and remarkable NIR-Ⅱ image-guided surgery in dimethylbenzanthracene(DMBA)-induced spontaneous breast tumor rats.This report presents the first tumor-homing peptide-based NIR-Ⅱ probe to diagnose transplantable and spontaneous breast tumors by the active targeting.     

Syntheses,structures, luminescent and magnetic properties of two coordination polymers based on a fl exible multidentate carboxylate ligand

Two coordination polymers,{[Cu_3(tci)_2(DMAc)_3]-6DMAc 2H_2O}_n(1) and {[Cu_3(tci)_2(tpt)_2(H_2O)_2].2DMAc-2H_2O}_n(2)(H_3tci = tris(2-carboxyethyI)isocyanurate,tpt = 2,4,6-tris(4-pyridyl)-l,3,5-triazine,DMAc = N,/V-dimethylacetamide),have been constructed under solvothermal conditions.Both polymers were structurally characterized by single crystal X-ray diffraction,elemental analyses,IR spectra,thermogravimetric(TG) analyses and powder X-ray diffraction(RXPD).1 shows a(3,4)-connected 2D layer structure comprising Cu_2(CO_2)4 paddle-wheel units,which are further bridged by C-H…O interactions to give a 3D supramolecular network.The introduction of tpt produces different framework for 2 that comprises a dinuclear and a mononuclear Cu(Ⅱ) building units,which are further bridged together by tci~(3-) and tpt ligands to give a 4-connected 2D topological net.Adjacent 2D layers are packed together via C-H…O interactions and π…π stacking interactions to form a 3D supramolecular structure.In addition,the luminescent properties and the solid-state UV-vis spectra of 1 and 2 were explored.Furthermore,antiferromagnetic exchange interactions were unveiled in the Cu_2(COO)_4 units of 1.     

Reaction of (dichloro)(1,5-cyclooctadiene)platinum(II) with dimethyl diazomethylphosphonate. Crystal structure analysis of a bis-insertion product, (R,R)-bis[chloro(dimethoxyphosphonyl)methyl]-(1,5-cyclooctadiene)platinum(II)

The reaction of dichloro(1,5-cyclooctadiene)platinum(II), 1 with dimethyl diazomethylphosphonate, 2, results in the formation of products of insertion of the carbene moiety into one or both PtCl bonds. An X-ray diffraction study of a crystal obtained from the major bis-insertion product of this reaction shows it to be (R,R)-bis[chloro(dimethoxyphosphonyl)methylyl](1,5-cyclooetadiene)platinum(II), 5. The space group is polar indicating that spontaneous resolution has occurred upon crystallization.     

Solid state properties of 1,2-epoxy-3-(2-methoxyphenyloxy)-propane—valuable intermediate in non-racemic drug synthesis

Racemic 1,2-epoxy-3-(2-methoxyphenyloxy)-propane 1 undergoes spontaneous resolution upon crystallization. This fact is confirmed by coincidence of the IR spectra of racemic and scalemic crystalline samples of 1, by thermal analysis (single eutectic V-shape binary melting phase diagram), and X-ray analysis (space group P2₁2₁2₁, Z = 4). Racemic 1 could be resolved into (S)-(+)- and (R)-(−)-1 by a preferential crystallization procedure.     

Highly enantioselective enzymatic resolution of aromatic β-amino acid amides with Pd-catalyzed racemization

The kinetic resolution of an aromatic β-amino acid amide 3a–d via N-acylation was explored with two lipases, Candida antarctica lipase A (CALA) and Pseudomonas stutzeri lipase (PSL). The PSL-catalyzed resolution proceeded with excellent enantioselectivity (E = >400) to give both acylated products and unreacted substrates in enantiopure forms. Three additional aromatic β-amino acid amides 3b–d were also resolved by PSL with a high level of enantioselectivity (E = >200). The PSL-catalyzed resolution of 3a was coupled with a Pd-catalyzed racemization to obtain enantiopure N-acylated product (R)-4a (>99% ee) in high yield (90%).     

Disordered structures,vibrational spectroscopy,thermal behavior,and electrical properties of two new tetrachlorometallates complexes [(CH3CH2CH2)4N]2MIICl4 with MII = Co and Mn

The two new hybrids single crystals having the general formula [(CH₃CH₂CH₂)₄N]₂M^IICl₄ with M^II = Co (1) and Mn (2) have been synthetised by the slow evaporation process in aqueous solutions. In this article, these compounds were described by the following characterization techniques: X-rays diffraction, thermal analysis (TGA-TDA), vibrational spectroscopy, nuclear magnetic resonance (NMR), and electrical properties. From the crystallographic study, the crystals (1) and (2) have been disclosed to be crystallized too in the centrosymmetric monoclinic systems, with space group P2₁/c (Z = 4) and C2/c (Z = 8), respectively. Their crystal structures consist of [MCl₄]²⁻ anions and two different cations [(CH₃CH₂CH₂)₄N]⁺, which are connected by a three dimensional network of C-H···Cl hydrogen bonds. In both crystals, each M^II center atom being surrounded by four chloride ligands forming a slightly distorted tetrahedral geometry. The tetrahedral [CoCl₄]²⁻ is ordered, while the tetrahedral [MnCl₄]²⁻ is disordered. Some tetrapropylammonium cations of these compounds are found to be disordered. The thermal analysis studies made in the temperature range (298–473 K) did not show any phase transition for the two crystals. Furthermore, the electrical properties of the two compounds are studied by using the complex impedance spectroscopy technique in the temperature and frequency field varied of 290–363 K and 1 kHz–13 MHz, respectively.     

Two distinct manganese(II) complexes with hexadentate 1,3-propanediaminetetraacetate ligand: The ability of metal(II) complexes with 1,3-pdta ligand to form solid solutions

The ability of Mn(II) ion to form two distinctly different complexes with 1,3-propanediaminetetraacetate (1,3-pdta) ligand has been demonstrated by performing X-ray analyses of their crystalline Mg(II) salts. The two types of Mn(II) complexes have been obtained by different synthetic routes and their crystals constitute, respectively, the solid solution of the composition [Mg(H₂O)₆][Mg_0.5Mn_0.5(1,3-pdta)] · 2H₂O (1) and the ordered crystals of the composition [Mg(H₂O)₆][Mn(1,3-pdta)(H₂O)] · 2H₂O (2). In both, six- 1 and seven-coordinated 2 Mn(II) complexes the 1,3-pdta ligand acts as a hexadentate. As 2 makes the second example of the seven-coordinated 1,3-pdta complex with divalent transition metal ion, the other being the [Mg(H₂O)₆][Cd(1,3-pdta)(H₂O)] · 2H₂O (3) complex, the paper reports the results of X-ray investigations of both of these complexes at 130 K.     

Synthesis of enantiomeric bridgehead substituted bisnoradamantane derivatives

The preparation of (+)- and (−)-12 by resolution of (±)-12 with (R)-N-phenylpantolactam, (R)-13, is described. From (+)- and (−)-12 a series of chiral bisnoradamantane derivatives, whose chirality stems from substitution at the bridgehead positions, have been obtained in both enantiomeric forms.     

Enantio- and diastereo-convergent synthesis of (2R,5R)- and (2R,5S)-Pityol through enzyme-triggered ring closure

A short chemoenzymatic synthesis of the (2R,5S)- and (2R,5R)-stereoisomer of the bark beetle pheromone Pityol 1 was achieved from (±)-Sulcatol 2 in an enantio- and diastereo-convergent fashion without the formation of any ‘unwanted’ stereoisomer. The key steps include: (i) lipase-catalyzed deracemization of (±)-2 using kinetic resolution coupled to an in-situ inversion or, alternatively, dynamic resolution using combined lipase- and Ru-catalysis; and (ii) creation of the second stereogenic center by an epoxide hydrolase-catalyzed diastereo-convergent hydrolysis of a haloalkyl oxirane, followed by spontaneous ring closure to form 1 in a stereoselective fashion.     

Enantioselective enzymatic acylation of 1-(3′-bromophenyl)ethylamine

An efficient biocatalytic process has been developed for the resolution of 1-(3′-bromophenyl)ethylamine (RS)-1 by way of enantioselective lipase-mediated (R)-selective acylation with ethyl 2-methoxyacetate to afford (S)-amine (S)-1 and (R)-2″-methoxyacetamide ((R)-2) in 91–95% and 90–92% isolated yield, respectively, and both with >99% ee.     

Solid state properties and effective resolution procedure for guaifenesin, 3-(2-methoxyphenoxy)-1,2-propanediol

Racemic expectorant guaifenesin, 3-(2-methoxyphenoxy)-1,2-propanediol 2 undergoes spontaneous resolution upon crystallization. This fact is confirmed by thermal analysis (single eutectic V-shape binary melting phase diagram, adequate entropy and free energy characteristics). Racemic 2 could be effectively resolved into (S)- and (R)-2 by a preferential crystallization procedure. Single enantiomer drugs levomoprolol and levotensin were obtained by starting from enantiomeric 2 through the sulfite route.     

Synthesis, characterizations and crystal structures of new organoantimony(V) complexes with various isomers of fluoromethylbenzoate ligands

Six new organoantimony(V) complexes containing various isomers of fluoromethylbenzoate ligands [RC₆H₃COO]₂SbPh₃ and [RC₆H₃COO]SbPh₄ [R = 3-F-4-(CH₃) (1, 4), 4-F-2-(CH₃) (2, 5), 5-F-2-(CH₃) (3, 6)] have been synthesized by the reactions of triphenylantimony(V) dichloride or tetraphenylantimony(V) bromide with various isomers of fluoromethylbenzoate ligands in 1:2 or 1:1 stoichiometries. All the complexes have been characterized by elemental analysis, IR and NMR [¹H, ¹³C and ¹⁹F] studies. The crystal structures of complexes 1, 3, 4, 5 and 6 have been determined by X-ray single crystal diffraction. The structure of complexes show that the five-coordinated antimony(V) atom adopts a distorted trigonal bipyramidal geometry. Furthermore, weak but significant intermolecular C–H···O, C–H···F hydrogen bonds, C–H···pi stacking lead to aggregation and assembly of these complexes into 1D and 2D supramolecular frameworks.     

Lipase-catalyzed kinetic and dynamic kinetic resolution of 1,2,3,4-tetrahydroisoquinoline-1-carboxylic acid

A dynamic kinetic resolution method for the preparation of enantiopure 1,2,3,4-tetrahydroisoquinoline-1-carboxylic acid (R)-2 was developed involving the CAL-B-catalyzed enantioselective hydrolysis of the corresponding ethyl ester (±)-1 in toluene/acetonitrile (4:1) containing 1 equiv of added water and 0.25 equiv of dipropylamine. This method allowed the preparation of (R)-2 (ee = 96%) with 80% isolated yield. The kinetic resolution of (±)-1 in diisopropyl ether at 3 °C afforded both enantiomers with ee ⩾92%.     

Preparation of isoxazolidinyl nucleoside enantiomers by lipase-catalysed kinetic resolution

An efficient biocatalytic procedure to obtain chiral N,O-nucleoside derivatives consisting of a lipase-catalysed resolution of the corresponding racemates in organic solvent has been developed. Enantioselective esterification of thymine and cytosine derivatives, (±)-9a and (±)-9b, has been investigated by comparing the efficiency of different lipases and acyl donors. Since esterification of (±)-9a and (±)-9b, occurred with low enantioselectivity (E ? 14) in the presence of the lipases considered, for preparative purposes we resorted, with success, to a double sequential kinetic resolution, using Lipozyme IM as the best catalyst. This approach enables us to obtain all the enantiomers with ee ? 95%. The absolute configuration of the new chiral N-acetyl cytosine derivative 9b was established by circular dichroism spectroscopy.     

Enzymatic resolution of racemic sulcatol by lipase from Candida Antarctica in a large scale

Large scale enzymatic resolution of racemic sulcatol 2 has been useful for stereoselective biocatalysis. This reaction was fast and selective, using vinyl acetate as donor of acyl group and lipase from Candida antarctica (CALB) as catalyst. The large scale reaction (5.0 g, 39 mmol) afforded high optical purities for S-(+)-sulcatol 2 and R-(+)-sulcatyl acetate 3, i.e., ee > 99 per cent and good yields (45 per cent) within a short time (40 min). Thermodynamic parameters for the chemoesterification of sulcatol 2 by vinyl acetate were evaluated. The enthalpy and Gibbs free energy values of this reaction were negative, indicating that this process is exothermic and spontaneous which is in agreement with the reaction obtained enzymatically.     

Chemoenzymatic synthesis of piperoxan,prosympal, dibozane,and doxazosin

The synthesis of both enantiomers of 1,4-benzodioxan-2-carboxylic acid 1, a key synthetic intermediate for the therapeutic agents piperoxan, prosympal, dibozane, and doxazosin was achieved with good yields and high enantioselectivities via the Arthrobacter sp. lipase catalyzed kinetic resolution of ester (±)-17a. The influence of the co-solvents and the immobilization of the lipase upon kinetic resolution demonstrated that immobilized whole cells, in the presence of n-butanol as a co-solvent, resulted in the optimal resolution of the substrate (ee ～99%, E = 535) at 258 mmol (50 g/L) substrate concentration.     

Bis(3-pyridyl)methylvinylsilane (L1) and 1,2-di(3-quinolyl) dimethyl disilane (L2): Synthesis and complexation reactions. Anion controlled solid state structures of cationic Ag(I)-L1 complex

3-Bromopyridine and 3-bromoquinoline on reaction with n-butyllithium give lithiated products which on reaction with dichloromethylvinylsilane and 1,2-dichlorodimethyldisilane at −78 °C result in the ligands bis(3-pyridyl)methylvinylsilane (L1) and 1,2-di(3-quinolyl)dimethyl disilane (L2). The complexation reactions of both these ligands with Ag(I), Pd(II) and Cu(II) have been explored. The ¹H, ¹³C{¹H} and ²⁹Si{¹H}NMR and IR spectra of both the ligands and their metal complexes have been found characteristic. The complex of L1 with silver(I), [Ag(L1)]ClO₄ (1) gives suitable single crystals characterized by X-ray diffraction. Its structure consists of two dimensional sheets, having 25-membered metallamacrocycle ring, in which Ag has distorted tetrahedral geometry and is bonded to vinyl (η²) group. On reacting AgCF₃SO₃ with L1 and subjecting the single crystals of the resulting complex to X-ray diffraction it has been found that contrary to 1 there is no bond between vinyl group and silver, resulting in infinite molecular strands, in which coordination geometry of silver is distorted trigonal planar. anion acts as a bridge between two molecular strands through F?H (aromatic) and Ag?O secondary interactions. The Ag-C distances in 1 are 2.309(5) and 2.350(12) Å. The CC bond length does not exhibit significant change on bonding with silver in 1.