Conformation of receptor-associated PGI2: An investigation by molecular modeling

Summary To elucidate the conformation of receptor-associated prostacyclin (PGI₂), we first performed structure-activity correlation analysis of over 200 PGI₂ analogues and derived from this analysis several crucial features pertaining to structural requirements for PGI₂ activity [Ah-lim Tsai and Kenneth K. Wu, Eicosanoids, 2 (1989) 131–143]. These structural features proved to be useful guidelines for selecting model molecules for further investigations by molecular mechanics. By properly selecting four analogues with either rigid or uniquely oriented -side chain structure for geometric fitting, we succeeded in maximally minimizing the degree of freedom of the carboxylate terminus of PGI₂. We were able to define the spatial relationship among the four critical functional groups, i.e., C1-COOH, C6a-O, C11-OH and C15-OH. More information is needed, however, to define the geometry of the -side chain, particularly for the moiety beyond C15. Nevertheless, results from structure-activity correlation analysis and molecular modeling provide useful information regarding the conformation of receptor-associated PGI₂, which assumes an elongated conformation instead of the traditional hairpin structure.     

Stereocontrolled synthesis of 7-hydroxy- and 7-acetoxy-PGI2: New stable PGI2 analogues

Stable analogues of PGI₂, 7-hydroxy- and 7-acetoxy-PGI₂, were synthesized from protected PGI₂ methyl ester $\text{1b}$via sulfoxides $\text{6a}$, $\text{6b}$ through stereocontrolled sulfoxide-sulfenate rearrangement.     

Preparative resolution of a key intermediate for the synthesis of optically active m-phenylene PGI2 derivatives

A key intermediate for the synthesis of optically active m-phenylene PGI₂ derivatives was efficiently resolved on a preparative scale by diastereomeric salt formation method using (+)-cis-N-benzyl-2-(hydroxymethyl)cyclohexylamine ((+)-cis-amine) as a resolving agent.     

An electron transfer model for PGI biosynthesis

A biomimetic conversion of the endoperoxide 1b to prostacyclin (PGI₂) analogs is achieved with the aid of ferrous ion catalysis.     

Analogues of prostacyclin (PGI2) modified in the 2-oxabicyclo[3.3.0]octane fragment (review)

A review is given of the synthetic analogs of the prostacyclins having greater chemical and metabolic stability than prostacyclin itself. Possible routes for synthesis are discussed.This review is an expanded version of the plenary lecture of the authors at the 3rd All-Union Conference on Synthetic and Applied Studies of Prostaglandins [in Russian], Ufa (1984).Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 579–595, May, 1986.     

Preparative resolution of 2-methyl-4-hexynic acid for the synthesis of optically active m-phenylene PGI2 derivatives and determination of their absolute configuration

Racemic 2-methyl-4-hexynic acid, which is a starting material for the ω-side chain of the PGI₂ derivatives, Beraprost and Iloprost, was efficiently resolved on a preparative scale by diastereomeric salt formation using quinine and cinchonidine as resolving agents. Their absolute configuration was determined by X-ray analyses of Beraprost derivatives.     

The confirmation of accurate combination of functional and basis set for transition‐metal dimers: Fe2, Co2, Ni2, Ru2, Rh2, Pd2, Os2, Ir2, and Pt2

Eight kinds of density functionals named B3LYP, PBE1PBE, B1B95, BLYP, BP86, G96PW91, mPWPW91, and SVWN along with two different valence basis sets (LANL2DZ and CEP‐121g) are employed to study the transition‐metal dimers for the elements of group VIII. By comparing the equilibrium bond distances, vibrational frequencies, and dissociation energies of the ground state of these dimers with the available experimental values and theoretical data, we show that the “pure” DFT methods (G96PW91, BLYP, and BP86) with great‐gradient approximation always give better results relative to the hybrid HF/DFT schemes (B3LYP, PBE1PBE, and B1B95). The striking case found by us is that the G96PW91 functional, which is not tested in previous systemic studies, always predicts the dissociation energy to be well. The Ru₂ and Os₂ dimers are sensitive to not only the functionals employed but also the valence basis sets adopted. The natural bond orbital population is analyzed, and the molecular orbitals of the unpaired electrons are determined. Furthermore, our results indicate that the s and d orbitals of these dimers always hybridize with each other except for Rh₂ and Pt₂ molecules. And by analyzing the electron configuration of the bonding atom, the dissociation limit of the ground state is obtained. © 2008 Wiley Periodicals, Inc. Int J Quantum Chem, 2008     

Synthesis of 2, 2, 5, 5-tetramethyltetrahydrothiophene

Under the conditions of the Grignard reaction, 2, 5-dimethyl-2, 5-hexanediol has been obtained from diethyl succinate. Under the action of sulfuric acid, the latter has been cyclized to 2, 2, 5, 5-tetramethyl-tetrahydrofuran which, in its turn, by treatment with phosphorus pentasulfide, has given 2, 2, 5, 5-tetramethyltetrahydrothiophene. Its reaction with methyl iodide has given 2, 2, 5, 5-tetramethyltetrahydrothiophene methiodide.     

Nouvelle Synthese Des 2-Thioxoethylphosphonates, 2- mercaptovinylphosphonates, 2-Phosphoryl-3-thioxopropanoates, 2-Thiomethylvinylphosphonates, 2-Thioethoxycarbonylmethylvinylphosphonates

The cyanomethylphosphonates 1 and the ethyl phosphoacetates 2 were reacted with some fluorophenylisothiocyanates to give the 2-thioxoethylphosphonates 3 in tautomeric equilibrium with the corresponding 2-mercaptovinylphosphonates 3 ′ and the 2-phosphoryl-3-thioxopropanoates 4 , respectively. Reaction of the cyanomethylphosphonates 1 with fluorophenylisothiocyanates in presence of methyliodide furnished the 2- thiometylvinylphosphonates 5 . The 2-mercaptovinylphosphonates 3 ′ reacted with ethyl chloroacetate in refluxing ethanol in the presence of triethylamine to give S-substitued derivatives 6 .     

IR matrix spectra of CsNO2, RbNO2, KNO2, and NaNO2. The structure of CsNO2

The IR spectra of alkali nitrites were studied in Ar matrices at the temperature of 7 K. The spectra of CsNO₂ were investigated with the aid of ¹⁵N and ¹⁸O isotopes in order to determine the structure of the gaseous molecules. The IR spectra of ¹⁸O-enriched CsNO₂ samples were recorded and the results interpreted by means of normal coordinate calculations. CsNO₂ has a planar ring structure of C_2v, symmetry. The bond angle ONO of this molecule was calculated to be 116 ± 5°. NaNO₂ as well as the remaining alkali nitrites have C_2v, symmetry structures. Far-IR spectra of alkali nitries were recorded in order to measure the interionic stretching vibrations; in some case low-frequency bands were observed and assigned to the A₁ and B₁ interionic stretching modes.     

Structural chemistry of Ba2CdS3, Ba2CdSe3, BaCdS2, BaCu2S2 and BaCu2Se2

The structures of all compounds were determined from three dimensional single crystal X-ray diffraction data and refined by least squares. Ba₂CdS₃ and Ba₂CdSe₃ are isostructural, Pnma, a = 8.9145(6)Å, b = 4.3356(2)Å, c = 17.2439(9)Å for the former compound and a = 9.2247Å, b = 4,4823(6)Å, c = 17.8706(11)Å for the latter, z = 4, R = 0.0751 and R = 0.0462, respectively. The compounds are isostructural with the previously reported Mn analogues and with K₂AgI₃. Cd ions are in tetrahedral environment and the tetrahedra form infinite linear chains by corner sharing. Ba ions are in 7-fold coordination in which 6 anions form a trigonal prism and 1 anion caps one of the rectangular faces. BaCdS₂, Pnma, a = 7.2781(3)Å, b = 4.1670(1)Å, c = 13.9189(6)Å, z = 4, R = 0.0685. Cd ions can be considered to have a triangular planar coordination with CdS distances of 2.47 and 2.53 Å (twice). Two additional S ions are at 2.89 and 3.22 Å to complete a triangular bipyramidal configuration. Ba is in 7-fold coordination with the anions forming a trigonal prism which is capped on one rectangular face. The compound is isostructural with BaCdO₂ and is related to the structure of BaMnS₂. BaCdSe₂ could not be prepared. BaCu₂S₂ and BaCu₂Se₂ are isostructural, Pnma, a = 9.3081(4)Å, b = 4.0612(3)Å, c = 10.4084(5)Å for the sulfide and a = 9.5944(6)Å, b = 4.2142(4)Å, c = 10.7748(8)Å for the selenide, z = 4, R = 0.0634 and 0.0373, respectively. Ba ions are in the usual 7-fold, capped hexagonal prism, coordination. However, 9 Cu ions also can be considered to form a trigonal prism with all rectangular faces capped, around Ba since the BaCu distances range from 3.24 to 3.54 Å for the sulfide and from 3.37 to 3.67 Å for the selenide. One of the Cu ions is in a very distorted tetrahedral environment and the second one is located in a more regular tetrahedral configuration of the anions. Two independent infinite chains of tetrahedra are present. They are formed by sharing of two adjacent edges of each tetrahedron and then these chains in turn are linked by corner sharing into a three-dimensional network of tetrahedra.     

Reactions of 1,3-dioxacycloalkanes and their 2-arsena, 2-bora, 2-germa, 2-sila,and 2-thia analogs with nitriles

New reactions of five-, six-, and seven-membered 1,3-dioxacycloalkanes and their 2-arsena, 2-bora, 2-germa, 2-sila, and 2-thia analogs with nitriles giving rise to 1,3-oxazacycloalkanes and then to amino alcohols are surveyed. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1499–1507, July, 2005.     

The metabolic profile of lemon juice by proton HR-MAS NMR: the case of the PGI Interdonato Lemon of Messina

We have studied by means of High Resolution Magic Angle Spinning Nuclear Magnetic Resonance (HR-MAS NMR) the metabolic profile of the famous Sicilian lemon known as 'Interdonato Lemon of Messina PGI’. The PGI Interdonato Lemon of Messina possesses high organoleptic and healthy properties and is recognised as one of the most nutrient fruits. In particular, some of its constituents are actively studied for their chemo-preventive and therapeutic properties. In this paper, we have determined by means of HR-MAS NMR spectroscopy the molar concentration of the main metabolites constituent the juice of PGI Interdonato Lemon of Messina in comparison with that of the not-PGI Interdonato Lemon of Turkey. Our aim is to develop an analytical technique, in order to determine a metabolic fingerprint able to reveal commercial frauds in national and international markets.     

Gaseous HgH2, CdH2, and ZnH2

Gaseous HgH2, CdH2, and ZnH2 molecules were synthesized by the direct gas-phase reaction of excited mercury, cadmium, and zinc atoms with molecular hydrogen. The molecules were identified by their high-resolution infrared emission spectra, and the metal-hydrogen bond lengths were determined from the rotational analysis of the antisymmetric stretching fundamental bands.     

CO2 laser-induced decomposition of propan-2-ol,butan-2-ol,pentan-2-ol,pentan-3-ol,and hexan-2-ol

The pulsed CO₂ laser-induced decompositions of propan-2-ol, butan-2-ol, pentan-2-ol, pentan-3-ol, and hexan-2-ol in the gas phase have been investigated. Like ethanol which we examined previously [1] the absorption cross section of propan-2-ol for pulsed 9R14 radiation increases with pressure at low pressures, an effect attributed to rotational hole-filling. In contrast the absorption cross section of butan-2-ol (10R24) has only a small pressure dependence and those of pentan-2-ol (9R26), pentan-3-ol (10R14), and hexan-2-ol (9P20) show little or no variation with pressure in the range 0.1–5.0 torr. Decomposition products have been investigated at low pressure where the excitation of the alkanols was essentially collision free. The observed products for all the alkanols can be rationalized on the basis of primary dehydration and C? C fission channels, with minor contributions from other molecular eliminations. © 1994 John Wiley & Sons, Inc.     

Sulfur and chlorine K-shell x-ray absorption spectra of SCl2, S2Cl2, SOCl2, and SO2Cl2

The X-ray absorption spectra of dichlorosulfide (SCl₂), dichlorodisulfide (S₂Cl₂), thionyl chloride (SOCl₂) and sulfuryl chloride (SO₂Cl₂) have been recorded with synchrotron radiation in the regions of S 1s and Cl 1s excitation and ionization. Ionization current spectra of SOCl₂ and SO₂Cl₂ in the Cl 1s regions are also presented. The main spectral features are assigned to K-shell excitations to σ^* orbitals associated with the SCl, SS and SO bonds in these molecules.