The monohydrates of the four polar dipeptides l‐seryl‐l‐asparagine,l‐seryl‐l‐tyrosine,l‐tryptophanyl‐l‐serine and l‐tyrosyl‐l‐tryptophan

The crystal structures of the four dipeptides l ‐seryl‐l ‐asparagine monohydrate, C₇H₁₃N₃O₅·H₂O, l ‐seryl‐l ‐tyrosine monohydrate, C₁₂H₁₆N₂O₅·H₂O, l ‐tryptophanyl‐l ‐serine monohydrate, C₁₄H₁₇N₃O₄·H₂O, and l ‐tyrosyl‐l ‐tryptophan monohydrate, C₂₀H₂₁N₃O₄·H₂O, are dominated by extensive hydrogen‐bonding networks that include cocrystallized solvent water molecules. Side‐chain conformations are discussed on the basis of previous observations in dipeptides. These four dipeptide structures greatly expand our knowledge on dipeptides incorporating polar residues such as serine, asparagine, threonine, tyrosine and tryptophan.     

Simultaneous determination of NG‐monomethyl‐l‐arginine,NG,NG‐dimethyl‐l‐arginine,NG,NG′‐dimethyl‐l‐arginine,and l‐arginine using monolithic silica disk‐packed spin columns and a monolithic silica column

We have developed and validated a high‐performance liquid chromatography method that uses monolithic silica disk‐packed spin columns and a monolithic silica column for the simultaneous determination of N^G‐monomethyl‐l ‐arginine, N^G,N^G‐dimethyl‐l ‐arginine, and N^G,N^G′‐dimethyl‐l ‐arginine in human plasma. For solid‐phase extraction, our method employs a centrifugal spin column packed with monolithic silica bonded to propyl benzenesulfonic acid as a cation exchanger. After pretreatment, the methylated arginines are converted to fluorescent derivatives with 4‐fluoro‐7‐nitro‐2,1,3‐benzoxadiazole, and then the derivatives are separated on a monolithic silica column. l ‐Arginine concentration was also determined in diluted samples. Standard calibration curves revealed that the assay was linear in the concentration range 0.2–1.0 μM for methylated arginines and 40–200 μM for l ‐arginine. Linear regression of the calibration curve yielded equations with correlation coefficients of 0.999 (r²). The sensitivity was satisfactory, with a limit of detection ranging from 3.75 to 9.0 fmol for all four compounds. The RSDs were 4.3–4.8% (intraday) and 3.0–6.8% (interday). When this method was applied to samples from six healthy donors, the detected concentrations of N^G‐monomethyl‐l ‐arginine, N^G,N^G‐dimethyl‐l ‐arginine, N^G,N^G′‐dimethyl‐l ‐arginine and l ‐arginine were 0.05 ± 0.01, 0.41 ± 0.07, 0.59 ± 0.11, and 83.8 ± 30.43 μM (n = 6), respectively.     

Synthesis and characterization of polyamides containing octadecanedioic acid: Nylon‐2,18, nylon‐3,18, nylon‐4,18, nylon‐6,18, nylon‐8,18, nylon‐9,18, and nylon‐12,18

High‐aliphatic‐content linear nylons were produced with an 18‐carbon diacid with diamines containing both odd and even methylene segments. The resulting polymers were characterized with viscosimetric, thermal, and spectroscopic techniques. Solid‐state ¹⁵N NMR was used to determine the nylon crystalline form present. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 936–945, 2005     

UPLC‐HR‐MS/MS‐based determination study on the metabolism of four synthetic cannabinoids,ADB‐FUBICA,AB‐FUBICA,AB‐BICA and ADB‐BICA,by human liver microsomes

Since 2012, several cannabimimetic indazole and indole derivatives with valine amino acid amide residue have emerged in the illicit drug market, and have gradually replaced the old generations of synthetic cannabinoids (SCs) with naphthyl or adamantine groups. Among them, ADB‐FUBICA [N‐(1‐amino‐3,3‐dimethyl‐1‐oxobutan‐2‐yl)‐1‐(4‐fluorobenzyl)‐1H–indole‐3‐carboxamide], AB‐FUBICA [N‐(1‐amino‐3‐methyl‐1‐oxobutan‐2‐yl)‐1‐(4‐fluorobenzyl)‐1H–indole‐3‐carboxamide], AB‐BICA [N‐(1‐amino‐3‐methyl‐1‐oxobutan‐2‐yl)‐1‐benzyl‐1H‐indole‐3‐carboxamide] and ADB‐BICA [N‐(1‐amino‐3,3‐dimethyl‐1‐oxobutan‐2‐yl)‐1‐benzyl‐1H‐indole‐3‐carboxamide] were detected in China recently, but unfortunately no information about their in vitro human metabolism is available. Therefore, biomonitoring studies to screen their consumption lack any information about the potential biomarkers (e.g. metabolites) to target. To bridge this gap, we investigated their phase I metabolism by incubating with human liver microsomes, and the metabolites were identified by ultra‐performance liquid chromatography–high resolution–tandem mass spectrometry. Metabolites generated by N‐dealkylation and hydroxylation on the 1‐amino‐alkyl moiety were found to be predominant for all these four substances, and others which underwent hydroxylation, amide hydrolysis and dehydrogenation were also observed in our investigation. Based on our research, we recommend that the N‐dealkylation and hydroxylation metabolites are suitable and appropriate analytical markers for monitoring their intake.     

A Novel Conversion of 2, 4‐Diaryl‐2, 3‐dihydro‐1 H‐1, 5‐benzodiazepines into 2, 4‐Diaryl‐3 H‐1, 5‐benzodiazepines

A novel conversion of 2, 4‐diaryl‐2, 3‐dihydro‐1 H‐1, 5‐benzodiazepins into 2, 4‐diaryl‐3 H‐1, 5‐benzodiazepines by the reaction with m‐chloroperbenzoic acid (MCPBA) was reported.     

2, 4‐Dimethylpenta‐1, 3‐dien‐ und 2, 4‐Dimethylpentadienyl‐Komplexe des Rhodiums und Iridiums

2, 4‐Dimethylpenta‐1, 3‐diene and 2, 4‐Dimethylpentadienyl Complexes of Rhodium and Iridium The complexes [(η⁴‐C₇H₁₂)RhCl]₂ ( 1 ) (C₇H₁₂ = 2, 4‐dimethylpenta‐1, 3‐diene) and [(η⁴‐C₇H₁₂)₂IrCl] ( 2 ) were obtained by interaction of C₇H₁₂ with [(η²‐C₂H₄)₂RhCl]₂ and [(η²‐cyclooctene)₂IrCl]₂, respectively. The reaction of 1 or 2 with CpTl (Cp = η⁵‐C₅H₅) yields the compounds [CpM(η⁴‐C₇H₁₂)] ( 3a : M = Rh; 3b : M = Ir). The hydride abstraction at the pentadiene ligand of 3a , b with Ph₃CBF₄ proceeds differently depending on the solvent. In acetone or THF the “half‐open” metallocenium complexes [CpM(η⁵‐C₇H₁₁)]BF₄ ( 4a : M = Rh; 4b : M = Ir) are obtained exclusively. In dichloromethane mixtures are produced which additionally contain the species [(η⁵‐C₇H₁₁)M(η⁵‐C₅H₄CPh₃)]BF₄ ( 5a : M = Rh; 5b : M = Ir) formed by electrophilic substitution at the Cp ring, as well as the η³‐2, 4‐dimethylpentenyl compound [(η³‐C₇H₁₃)Rh{η⁵‐C₅H₃(CPh₃)₂}]BF₄ ( 6 ). By interaction of 2, 4‐dimethylpentadienyl potassium with 1 or 2 the complexes [(η⁴‐C₇H₁₂)M(η⁵‐C₇H₁₁)] ( 7a : M = Rh; 7b : M = Ir) are generated which show dynamic behaviour in solution; however, attempts to synthesize the “open” metallocenium cations [(η⁵‐C₇H₁₁)₂M]⁺ by hydride abstraction from 7a , b failed. The new compounds were characterized by elemental analysis and spectroscopically, 4b and 5a also by X‐ray structure analysis.     

Theoretical calculations on the mechanisms of the gas‐phase elimination kinetics of 2‐chloro‐1‐phenylethane, 3‐chloro‐1‐phenylpropane, 4‐chloro‐1‐phenylbutane, 5‐chloro‐1‐phenylpentane,and their corresponding chloroalkanes: The effect of the phenyl ring

The kinetics and mechanisms of the dehydrochlorination of 2‐chloro‐1‐ phenylethane, 3‐chloro‐1‐phenylpropane, 4‐chloro‐1‐phenylbutane, 5‐chloro‐1‐phenylpentane, and their corresponding chloroalkanes were examined by means of electronic structure calculation using density functional theory methods B3LYP/6–31G(d,p), B3LYP/6–31++G(d,p), MPW1PW91/6–31G(d,p), MPW1PW91/6–31++G(d,p), PBEPBE/6–31G(d,p), and PBEPBE/6–31++G(d,p). The potential energy surface was investigated for the minimum energy path. Calculated enthalpies and energies of activation are in good agreement with experimental values using the MPW1PW91 and B3LYP methods. The transition state of these reactions is a four‐centered cyclic structure. The reported experimental results proposing neighboring group participation by the phenyl group was not supported by theoretical calculations. The rate‐determining process in these reactions is the breaking of Cl? C bond. The reactions are described as concerted moderately polar and nonsynchronous. © 2011 Wiley Peiodicals, Inc. Int J Chem Kinet 43: 292–302, 2011     

Synthesis,characterization, and crosslinking of methacrylate‐telechelic PDMAAm‐b‐PDMS‐b‐PDMAAm copolymers

The synthesis and molecular characterization of a new amphiphilic conetwork (APCN) designed for silicone hydrogel use is described. The synthesis strategy, outlined in Scheme 1 , calls for the preparation, by the RAFT technique, of a new methacrylate‐telechelic amphiphilic pentablock, MA‐PHEA‐b‐PDMAAM‐b‐PDMS‐b‐PDMAAm‐b‐PHEA‐MA, and its crosslinking to the target APCN. The sketch shows the architecture of the APCN (dotted lines, PDMAAm; solid lines, PDMS; clusters, MA‐based crosslinking sites; see Fig. 3 ). All six synthesis steps proceed smoothly and efficiently, and the products are optically clear, colorless membranes exhibiting properties appropriate for ophthalmic use. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 4284–4290, 2007     

Rose Bengal‐Sensitized Photooxidation of the Dipeptides l‐Tryptophyl‐l‐Phenylalanine,l‐Tryptophyl‐l‐Tyrosine and l‐Tryptophyl‐l‐Tryptophan: Kinetics,Mechanism and Photoproducts¶

The Rose Bengal‐sensitized photooxidations of the dipeptides l ‐tryptophyl‐l ‐phenylalanine (Trp‐Phe), l ‐tryptophyl‐l ‐tyrosine (Trp‐Tyr) and l ‐tryptophyl‐l ‐tryptophan (Trp‐Trp) have been studied in pH 7 water solution using static photolysis and time‐resolved methods. Kinetic results indicate that the tryptophan (Trp) moiety interacts with singlet molecular oxygen (O₂(¹Δ_g)) both through chemical reaction and through physical quenching, and that the photooxidations can be compared with those of equimolecular mixtures of the corresponding free amino acids, with minimum, if any, influence of the peptide bond on the chemical reaction. This is not a common behavior in other di‐ and polypeptides of photooxidizable amino acids. The ratio between chemical (k_r) and overall (k_t) rate constants for the interaction O₂(¹Δ_g)‐dipeptide indicates that Trp‐Phe and Trp‐Trp are good candidates to suffer photodynamic action, with k_rlk_t values of 0.72 and 0.60, respectively (0.65 for free Trp). In the case of Trp‐Tyr, a lower k_rlk_t value (0.18) has been found, likely as a result of the high component of physical deactivation of O₂(¹Δ_g) by the tyrosine moiety. The analysis of the photooxidation products shows that the main target for O₂(¹Δ_g) attack is the Trp group and suggests a much lower accumulation of kynurenine‐type products, as compared with free Trp. This is possibly because of the occurrence of another accepted alternative pathway of oxidation that gives rise to 3a‐oxidized hydrogenated pyrrolo[2,3‐b]indoles.     

4,6‐Dinitro‐N,N′‐di‐n‐octylbenzene‐1,3‐diamine, 4,6‐dinitro‐N,N′‐di‐n‐undecylbenzene‐1,3‐diamine and N,N′‐bis(2,4‐dinitrophenyl)octane‐1,8‐diamine

4,6‐Dinitro‐N,N′‐di‐n‐octylbenzene‐1,3‐diamine, C₂₂H₃₈N₄O₄, (I), 4,6‐dinitro‐N,N′‐di‐n‐undecylbenzene‐1,3‐diamine, C₂₈H₅₀N₄O₄, (II), and N,N′‐bis(2,4‐dinitrophenyl)octane‐1,8‐diamine, C₂₀H₂₄N₆O₈, (III), are the first synthetic meta‐dinitroarenes functionalized with long‐chain aliphatic amine groups to be structurally characterized. The intra‐ and intermolecular interactions in these model compounds provide information that can be used to help understand the physical properties of corresponding polymers with similar functionalities. Compounds (I) and (II) possess near‐mirror symmetry, with the octyl and undecyl chains adopting fully extended anti conformations in the same direction with respect to the ring. Compound (III) rests on a center of inversion that occupies the mid‐point of the central C—C bond of the octyl chain. The middle six C atoms of the chain form an anti arrangement, while the remaining two C atoms take hard turns almost perpendicular to the rest of the chain. All three molecules display intramolecular N—H...O hydrogen bonds between the amine and nitro groups, with the same NH group forming a bifurcated intermolecular hydrogen bond to the nitro O atom of an adjacent molecule. In each case, these interactions link the molecules into one‐dimensional molecular chains. In (I) and (II), these chains pack so that the pendant alkyl groups are interleaved parallel to one another, maximizing nonbonded C—H contacts. In (III), the alkyl groups are more isolated within the molecular chains and the primary nonbonded contacts between the chains appear to involve the nitro groups not involved in the hydrogen bonding.     

Sulfenylation of heterocyclic 1,3‐dicarbonyl systems: 4‐Hydroxy‐2‐pyrones, 6‐hydroxy‐4‐pyrimidones, 4‐hydroxy‐2‐pyridones, 4‐hydroxy‐6‐pyridazinones,and 5‐hydroxy‐3‐pyrazolones

Anions of enolized heteroaromatic 1,3‐dicarbonyl systems, such as the title compounds 1, 9,14 , and 19 , react in dimethylformamide in the presence of potassium carbonate with diaryl disulfides 2 to yield arylsulfenyl derivatives ( 3, 10, 15, 20 ). The arylthiolate anions 4 formed in this reaction can be oxidized by air to yield the starting disulfides 2 again. Tetraalkylthiuram disulfides 7 react in the same manner to yield dialkylaminothiocarbonylthio derivatives ( 8, 13, 18 ) of the title compounds. Oxidation of the arylsulfenyl derivatives with hydrogen peroxide in sodium hydroxide solution usually leads to sulfoxides ( 5, 11, 16 ), whereas oxidation with peracetic acid affords sulfones ( 6, 12, 17 ).     

Superoxide Compounds of the Large Pseudo‐Alkali‐Metal Ions Tetramethylammonium, ‐Phosphonium,and ‐Arsonium

Compounds of the three large cations tetramethylammonium, tetramethylphosphonium, and tetramethylarsonium with the superoxide radical anion were synthesized by either metathesis or ion exchange in liquid ammonia. They were obtained from concentrated solutions as ammoniates in the form of long needle‐shaped single crystals. [N(CH₃)₄]‐(O₂)?3NH₃ crystallizes in the monoclinic crystal system, whereas the two compounds [E(CH₃)₄](O₂)?2NH₃ (E=P, As) are isostructural and belong to the orthorhombic crystal system. The cation–anion packing in all three crystal structures is related to the sodium chloride structure. All structures contain hydrogen bonds between the ammonia molecules and between ammonia and the superoxide. The solvent of crystallization was easily released from the crystals upon complete removal of the solvent from the reaction vessel, leading to polycrystalline samples. The Raman spectra of all three solvent‐free compounds show the symmetric stretching mode of the superoxide ion at about 1123 cm^?1. The desolvated [N(CH₃)₄](O₂) was investigated by powder X‐ray diffraction, and the crystal structure was solved by ab initio simulated annealing methods by using rigid‐body models of the constituent molecular ions. The superoxide ion shows rotational disorder. The magnetic susceptibility of tetramethylammonium superoxide follows the Curie–Weiss law with a high‐temperature effective magnetic moment of 1.66(3) μ_B and a paramagnetic Curie temperature of Θ=?13(6) K. Complementary electron paramagnetic resonance spectroscopy revealed that the average g factor is temperature‐dependent. It decreased from 2.15 at 10 K to 1.66 at 100 K, possibly due to the onset of rotational motion of the superoxide ion and in accordance with the lower‐than‐expected effective magnetic moment.     

The Recently Synthesized Dimagnesiabutadiene and the Analogous Dimetalla‐Beryllium, ‐Calcium, ‐Strontium,and ‐Barium Compounds

The 2014 synthesis of the remarkable dimagnesium compound Mg₂[C₄(CH₃)₂(Si(CH₃)₃)₂](C₃H₇)₂(C₄H₈O)₂ may point the way to a new chapter in alkaline earth organometallic chemistry. Accordingly, we have studied the known Mg compound and the analogous Be, Ca, Sr, and Ba structures. Although most of our theoretical predictions come from density functional methods, the latter have been benchmarked using coupled cluster theory including single, double, and perturbative triplet excitations, CCSD(T) using cc‐pVTZ basis sets. Among our most important predictions are the energies for dissociation to the butadiene plus the RM?MR [R=(C₃H₇)₂(C₄H₈O)₂; M=Be, Mg, Ca, Si, and Ba] entities. The most reliable predictions for the dissociation energies are 99–104 (Be), 85–93 (Mg), 90–99 (Ca), 83–92 (Sr), and 83–94 (Ba) kcal mol^?1. Thus, there is reason to anticipate that the four unknown compounds should be achievable synthetically. The predicted metal–metal distances (not single bonds) are 2.89 Å (Mg???Mg), 3.46 Å (Ca???Ca), 3.75 Å (Sr???Sr), and 4.04 Å (Ba???Ba). The separated RM?MR compounds have longer M?M distances but genuine metal–metal single bonds. This perhaps counter intuitive result is due to the presence of the bridging carbons in the alkaline earth butadiene compounds. All five compounds incorporate metal–carbon ionic interactions.     

One‐Pot,Three‐Component Sulfonimidamide Synthesis Exploiting the Sulfinylamine Reagent N‐Sulfinyltritylamine,TrNSO

Sulfonimidamides are increasingly important molecules in medicinal chemistry and agrochemistry, but their preparation requires lengthy synthetic sequences, which has likely limited their use. We describe a one‐pot de novo synthesis of sulfonimidamides from widely available organometallic reagents and amines. This convenient and efficient process uses a stable sulfinylamine reagent, N‐sulfinyltritylamine (TrNSO), available in one step on 10 gram scale, as a linchpin. In contrast to classical approaches starting from thiols or their derivatives, our TrNSO‐based approach facilitates the rapid assembly of the three reaction components into a variety of differentially substituted sulfonimidamides containing medicinally relevant moieties, including pyridines and indoles. Analogues of the sulfonamide‐containing COX‐2 inhibitor Celecoxib were prepared and evaluated.     

Synthesis and Structure of a 2, 8, 9‐Trioxa‐3, 5, 7‐trisila‐1‐titanaadamantane

The title compound has been prepared from [Ti(η⁵‐C₅Me₅)Cl₃] and cis‐cis‐(t‐BuSi(OH)—CH₂)₃ in hexane solution in the presence of Et₃N. The pale yellow complex was characterized by NMR and MS spectra, as well as by a crystal structure determination. The two crystallographic independent molecules in the triclinic unit cell (space group P1¯, No. 2, Z = 4) both have a nearly identical adamantane‐like TiO₃Si₃C₃ cage of approximate C_3v symmetry. The exocyclic C—C—C bond angles in the Cp‐ligand range from 123° to 129°. A quantum chemical calculation of the free molecule predicts this range to be 124° to 127°. The arrangement of the molecules in the crystal is characteristic for an offset face‐to‐face ππ stacking of the aromatic η⁵‐C₅Me₅ rings.     

2,3,3a,4,5a,6,7,8‐Octa­hydro‐5a‐methyl‐6,9‐methano‐1H,9H‐5‐oxa‐4‐aza­cyclo­penta­[c]­indene

The regio‐ and stereochemistry of the title compound, C₁₂H₁₅NO, has been established by X‐ray analysis. The molecular dimensions are normal.     

Synthesis,Bioactivity, and the Anion‐Binding Property of 2‐Sulfydryl‐1,3,4‐thiodiazole Derivatives

Two new compounds ( 1 and 2 ) containing 2‐sulfydryl‐1,3,4‐thiodiazole have been synthesized and optimized. They both showed wide antibacterial activity for colon bacillus, Staphylococcus aureus, S. albus, dysentery bacillus and inferior activity for Bacillus subtilis. In addition, their binding properties were evaluated for biologically important anions (F^–, Cl^–, Br^–, I^–, AcO^–, and H₂PO₄^–) by theoretical investigation, UV–vis, fluorescence, and ¹H NMR titration experiments, and they displayed strong binding ability for H₂PO₄^– without the interference of other anions tested. Especially the binding ability of compound 2 containing anthracene with H₂PO₄^– was 1000 times stronger than that of compound 1 containing nitrobenzene. Two compounds based on 2‐sulfydryl‐1,3,4‐thiodiazole have both properties of anion recognition and antibacterial activity.     

The effect of temperature on the stability of compounds used as UV‐MALDI‐MS matrix: 2,5‐dihydroxybenzoic acid, 2,4,6‐trihydroxyacetophenone, α‐cyano‐4‐hydroxycinnamic acid, 3,5‐dimethoxy‐4‐hydroxycinnamic acid,nor‐harmane and harmane

The thermal stability of several commonly used crystalline matrix‐assisted ultraviolet laser desorption/ionization mass spectrometry (UV‐MALDI‐MS) matrices, 2,5‐dihydroxybenzoic acid (gentisic acid; GA), 2,4,6‐trihydroxyacetophenone (THA), α‐cyano‐4‐hydroxycinnamic acid (CHC), 3,5‐dimethoxy‐4‐hydroxycinnamic acid (sinapinic acid; SA), 9H‐pirido[3,4‐b]indole (nor‐harmane; nor‐Ho), 1‐methyl‐9H‐pirido[3,4‐b]indole (harmane; Ho), perchlorate of nor‐harmanonium ([nor‐Ho + H]⁺) and perchlorate of harmanonium ([Ho + H]⁺) was studied by heating them at their melting point and characterizing the remaining material by using different MS techniques [electron ionization mass spectrometry (EI‐MS), ultraviolet laserdesorption/ionization‐time‐of‐flight‐mass spectrometry (UV‐LDI‐TOF‐MS) and electrospray ionization‐time‐of‐flight‐mass spectrometry (ESI‐TOF‐MS)] as well as by thin layer chromatography analysis (TLC), electronic spectroscopy (UV‐absorption, fluorescence emission and excitation spectroscopy) and ¹H nuclear magnetic resonance spectroscopy (¹H‐NMR). In general, all compounds, except for CHC and SA, remained unchanged after fusion. CHC showed loss of CO₂, yielding the trans‐/cis‐4‐hydroxyphenylacrilonitrile mixture. This mixture was unambiguously characterized by MS and ¹H‐NMR spectroscopy, and its sublimation capability was demonstrated. These results explain the well‐known cluster formation, fading (vanishing) and further recovering of CHC when used as a matrix in UV‐MALDI‐MS. Commercial SA (SA 98%; trans‐SA/cis‐SA 5 : 1) showed mainly cis‐ to‐trans thermal isomerization and, with very poor yield, loss of CO₂, yielding (3′,5′‐dimethoxy‐4′‐hydroxyphenyl)‐1‐ethene as the decarboxilated product. These thermal conversions would not drastically affect its behavior as a UV‐MALDI matrix as happens in the case of CHC. Complementary studies of the photochemical stability of these matrices in solid state were also conducted. Copyright © 2008 John Wiley & Sons, Ltd.