Synthesis and molecular and extended structures for a diaminonaphthalene-derived bis(amido)stannylene

The cyclic bis(amido)tin(II) compound Sn[1,8-((iPrN)2C10H6] (2) was isolated from the reaction of Li2[1,8-((iPrN)2C10H6] (1) and SnCl2. Solid-state structural analysis of 2 showed it to be a mononuclear species with a pyramidal Sn center as part of a nonplanar metallaheterocycle. The packing diagram of 2 revealed an extended one-dimensional head-to-tail chain structure with short intermolecular Sn/arene-C interactions. Computational examination of 2 (DFT/PW91 and MP2 with 6-31G* and 6-311G** basis functions) indicated that the optimum gas-phase structure of 2,which displays a Sn center in the plane of the naphthyl backbone with a slightly twisted metallaheterocycle, is approximately 24 kcal/mol lower in energy than the X-ray structure. The solid-state geometry of 2 is attributed to the intermolecular donation of the naphthalene pi-electrons to a Lewis acidic Sn center, which leads to the observed supramolecular structure. The crystal structure of 1 is also reported.     

Synthesis of some fused β‐carbolines including the first example of the pyrrolo[3,2‐c]‐β‐carboline system

Condensation of 1‐methyl‐β‐carboline‐3‐carbaldehyde with ethyl azidoacetate and subsequent thermolysis of the resulting azidopropenoate was used to [c] annulate a pyrrole ring onto the β‐carboline moiety, thus producing the first example of the pyrrolo[3,2‐c]‐β‐carboline ring system. The latter ring system results from cyclization at the C‐4 carbon, whereas cyclization at the N‐2 nitrogen atom also occurs to form a pyrazolo[3,2‐c]‐β‐carboline ring system. Condensation of β‐carboline‐1‐carbaldehyde with ethyl azidoacetate produced a non‐isolable intermediate, which immediately underwent cyclization, however in this case cyclization occurred via attack at the ester and the azide remained intact. The resulting 5‐azidocanthin‐6‐one was transformed to the first examples of 5‐aminocanthin‐6‐ones. β‐Carboline‐1,3‐dicarbaldehyde failed to give an acceptable reaction with ethyl azidoacetate, but did undergo selective condensation with dimethyl acetylene dicarboxylate at the C‐1 carbaldehyde with concomitant cyclization to form a highly functionalized 2‐formyl‐canthine derivative.     

Temperature requirements for thermal modulation in comprehensive two-dimensional gas chromatography

Temperature requirements for trapping and release of compounds in a cryogenic gas loop-type GC x GC modulator were determined. Maximum trapping temperatures on the uncoated, deactivated modulator capillary were determined for compounds from C4 (bp -0.5 degrees C) to C40 (bp 522 degrees C). The liquid-nitrogen cooled gas flow rate was reduced from a high of 15.5 to 1.5 SLPM over the range to achieve the required trapping temperature. Excessive cold jet flow rates caused irreversible trapping and peak tailing for semi-volatile compounds above C26. Alternate cold jet coolants were investigated. An ice water-cooled jet was able to trap compounds with boiling points from C18 (bp 316 degrees C) to C40 and a room temperature air-cooled jet was able to trap compounds from C20 (bp 344 degrees C) to C40. The hot jet produced launch temperatures approximately 40 degrees C hotter than the elution temperature with heating time constants of 8 to 27 ms. Modulated compound peaks were symmetrical with half-height peak widths of 43 to 56 ms for compounds with little second column retention, and 70 to 75 ms for compounds with more second column retention. The liquid nitrogen-cooled loop modulator with gas flow programming was used to produce a GC x GC chromatogram for a crude oil that contained compounds from C7 to C47.     

Kinetics and mechanism of *NO2 reacting with various oxidation states of myoglobin

Nitrogen dioxide ((*)NO(2)) participates in a variety of biological reactions. Of great interest are the reactions of (*)NO(2) with oxymyoglobin and oxyhemoglobin, which are the predominant hemeproteins in biological systems. Although these reactions occur rapidly during the nitrite-catalyzed autoxidation of hemeproteins, their roles in systems producing (*)NO(2) in the presence of these hemeproteins have been greatly underestimated. In the present study, we employed pulse radiolysis to study directly the kinetics and mechanism of the reaction of oxymyoglobin (MbFe(II)O(2)) with (*)NO(2). The rate constant of this reaction was determined to be (4.5 +/- 0.3) x 10(7) M(-1)s(-1), and is among the highest rate constants measured for (*)NO(2) with any biomolecule at pH 7.4. The interconversion among the various oxidation states of myoglobin that is prompted by nitrogen oxide species is remarkable. The reaction of MbFe(II)O(2) with (*)NO(2) forms MbFe(III)OONO(2), which undergoes rapid heterolysis along the O-O bond to yield MbFe(V)=O and NO(3-). The perferryl-myoglobin (MbFe(V)=O) transforms rapidly into the ferryl species that has a radical site on the globin ((*)MbFe(IV)=O). The latter oxidizes another oxymyoglobin (10(4) M(-1)s(-1) < k(17) < 10(7) M(-1)s(-1)) and generates equal amounts of ferrylmyoglobin and metmyoglobin. At much longer times, the ferrylmyoglobin disappears through a relatively slow comproportionation with oxymyoglobin (k(18) = 21.3 +/- 5.3 M(-1)s(-1)). Eventually, each (*)NO(2) radical converts three oxymyoglobin molecules into metmyoglobin. The same intermediate, namely MbFe(III)OONO(2), is also formed via the reaction peroxynitrate (O(2)NOO(-)/O(2)NOOH) with metmyoglobin (k(19) = (4.6 +/- 0.3) x 10(4) M(-1)s(-1)). The reaction of (*)NO(2) with ferrylmyoglobin (k(20) = (1.2 +/- 0.2) x 10(7) M(-1)s(-1)) yields MbFe(III)ONO(2), which in turn dissociates (k(21) = 190 +/- 20 s(-1)) into metmyoglobin and NO(3-). This rate constant was found to be the same as that measured for the decay of the intermediate formed in the reaction of MbFe(II)O(2) with (*)NO, which suggests that MbFe(III)ONO(2) is the intermediate observed in both processes. This conclusion is supported by thermokinetic arguments. The present results suggest that hemeproteins may detoxify (*)NO(2) and thus preempt deleterious processes, such as nitration of proteins. Such a possibility is substantiated by the observation that the reactions of (*)NO(2) with the various oxidation states of myoglobin lead to the formation of metmyoglobin, which, though not functional in the gas transport, is nevertheless nontoxic at physiological pH.     

Synthesis and structural investigation of N,N',N' '-trialkylguanidinato-supported zirconium(IV) complexes

The addition of 2 equiv of N,N',N' '-triisopropylguanidine (guanH(2)) to Zr(CH(2)Ph)(4) produced the bis(guanidinato)bis(benzyl)zirconium complex [((i)PrNH)C(N(i)Pr)(2)](2)Zr(CH(2)Ph)(2) (1). The mono(guanidinato) complex [((i)PrN)(2)C(NH(i)Pr)]ZrCl(3) (2) was accessible by the reaction of 2 equiv of guanH(2) with ZrCl(4). Guanidinium hydrochloride, [C(NH(i)Pr)(3)]Cl, is a byproduct of this reaction. When crystallized from THF, complex 2 was isolated as the THF adduct [((i)PrNH)C(N(i)Pr)(2)]ZrCl(3)(THF) (2-THF). The mixed cyclopentadienyl guanidinato complex [eta(5)-1,3-(Me(3)Si)(2)C(5)H(3)][((i)PrNH)C(N(i)Pr)(2)]ZrCl(2) (3) was prepared by treatment of [1,3-(Me(3)Si)(2)C(5)H(3)]ZrCl(3) with the in situ generated lithium triisopropylguanidinate salt. The reaction of guanH(2) with [1,3-(Me(3)Si)(2)C(5)H(3)]ZrMe(3) affords the dimethyl derivative [eta(5)-1,3-(Me(3)Si)(2)C(5)H(3)][((i)PrNH)C(N(i)Pr)(2)]ZrMe(2) (4). Definitive evidence for the molecular structures of these products is provided through single-crystal X-ray characterization of 1, 2-THF, and 3, which are presented. The extent of pi delocalization within the guanidinato ligand is discussed in the context of the metrical parameters obtained from these structural studies.     

Resonance-enhanced multiphoton ionization of molecular hydrogen via the E,F1Σg+ state: Photoelectron energy and angular distributions

Photoelectron energy and angular distributions are measured for the 2+1 multiphoton ionization process H₂ X¹Σ_g⁺ (ν = 0,J) + 2hv → E,F¹Σ_g⁺(ν_E,J_E = J) + hν → H₂⁺X²Σ_g⁺ (ν⁺) + e^?, for ν_E = 0, 1, or 2 and for J_E = 0 or 1 of the inner well of the double-minimum E,F state. Although a strong preference is found for ν⁺ = ν_E, the detailed H₂⁺ vibrational distribution does not exhibit Franck-Condon behavior, and the photoelectron angular distributions vary markedly with both the J_E value of the intermediate state and the ν⁺ value of the ion.     

Validation and application of a high-performance liquid chromatography/tandem mass spectrometry assay for sumatriptan in human plasma

A sensitive and convenient high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS) assay is described for the (5-HT(lB/lD)) receptor agonist sumatriptan in human plasma. Sumatriptan was recovered from plasma (81.8 +/- 6.8%) by liquid-liquid extraction. The mobile phase flow rate was 0.3 mL/min and consisted of methanol:water:formic acid (90:10:0.1, v/v/v). The analytical column (4.6 x 100 mm) was packed with Partisil C(8) (5 micro m). The standard curve was linear from 0.7 to 70.4 ng/mL (r(2) > 0.99). The lower limit of quantitation was 0.7 ng/mL. The assay was specific, accurate (percentage deviation from nominal concentrations were <15%), precise and reproducible (within- and between-day coefficients of variation <10.3%). Sumatriptan in plasma was stable over three freeze/thaw cycles and at room temperature for one day. The utility of the assay was demonstrated by following sumatriptan plasma concentrations in two healthy subjects for 8-12 h following a single 20 mg intranasal dose.     

The reaction of 4-(p-nitrobenzyl)pyridine with some electrophiles

The nucleophile 4-(p-nitrobenzyl)pyridine was allowed to react with four carcinogenic alkylating agents, chloromethyl methyl ether, bis(chloromethyl) ether, glycol sulfate and propane sultone, one carcinogenic acylating agent, N,N-dimethylcarbamyl chloride, and one noncarcinogenic electrophile, perchlorocyclobutenone. The structures of the major products formed, which are substituted pyridinium salts or 1,4-dihydropyridines, were determined.     

Blends of starch with ethylene vinyl alcohol copolymers: effect of water,glycerol, and amino acids as plasticizers

Blends of thermoplastic starch with poly(ethylene‐co‐vinyl alcohol) copolymer (EVOH) were melt extruded with water/glycerol as plasticizer and a series of amino acid additives. The biggest factor in end‐use mechanical properties proved to be the relative humidity (RH) during storage. Plasticized starch‐EVOH blends stored at 0 and 50% RH changed significantly over time, with, for example, the tensile strength (TS) of the glycerol‐plasticized blend increasing from 4.7 to 26.3 MPa over 8 weeks when maintained at 0% RH. In contrast, the TS of this same sample stored at 75% RH remained unchanged for 8 weeks. Amino acids provided relatively minor, but significant changes in mechanical properties with time. Based on TS, elongation‐to‐break, and modulus, it may be concluded that β‐alanine, sarcosine, and L ‐proline were more effective than glycerol at maintaining strong flexible blends. Increases in crystallinity and changes in morphology with time, as described by modulated DSC were correlated to these changes in mechanical properties. Published in 2007 by John Wiley & Sons, Ltd.     

Electrochemistry of 6-methyl-5,6,7,8-tetrahydropterin

The electrochemical oxidation of 6-methyl-5,6,7,8-tetrahydropterin (6-MTHP), the most effective of the synthetic aromatic amino acid hydroxylase pseudo cofactors, has been studied in aqueous solution over a wide pH range at a pyrolytic graphite electrode. The first electrooxidation of 6-WTHP occurs by a quasi-reversible 2e-2H⁺ reaction giving an unstable quinonoid-dihydropterin. The latter undergoes a first order chemical follow-up reaction yielding 6-methyl-7,8-dihydropterin (6-MDHP). At pH values ?5.6 6-MDHP forms an equilibrium mixture of a covalently hydrated species and non-hydrated species. The covalently hydrated form of 6-MDHP is electrooxidized in a 2e-2H⁺ quasi-reversible reaction to another unstable quinonoid that appears to undergo a two-step rearrangement to 6-methylpterin. Non-hydrated 6-MDHP is electrooxidized at the most positive potential in an irreversible 2e-2H⁺ reaction giving 6-methylpterin.