Synthesis of new carbamate derivatives of indole and their modification

Oximation of indoles having a methoxycarbonylamino group on C⁵ and an acyl group on C³ with hydroxylamine hydrochloride in the presence of pyridine gave the corresponding oximes. The reduction of the 3-C=O group with sodium tetrahydridoborate in the presence of sodium hydroxide was accompanied by removal of the methoxycarbonyl group at the pyrrole nitrogen atom with formation of racemic alcohols. 1,4-Addition of 1-(pyridin-3-yl)butane-1,3-dione to dimethyl 1,4-benzoquinone diimine N,N′-dicarboxylate in dioxane in the presence of sodium methoxide, followed by heating in boiling 22% hydrochloric acid, afforded methyl 2-methyl-5-(methoxycarbonylamino)-3-(pyridin-3-ylcarbonyl)-1H-indole-1-carboxylate. 3-(Dimethylamino)-1-(4-methyl-1,2,5-oxadiazol-3-yl)prop-2-en-1-one reacted with N,N′-bis(methoxycarbonyl)- and N,N′-bis(phenylsulfonyl)-1,4-benzoquinone diimines in methylene chloride and acetic acid, respectively, in the presence of BF₃ · Et₂O to produce indoles having a 1,2,5-oxadiazolylcarbonyl group on C₃.     

The glycosyl C1′—N9 bond of deoxyadenosine and deoxyguanosine: response to electrophilic attacks on the purinic nitrogen atoms

Self-consistent-field computations shed light on two relevant conformations of deoxyadenosine (dA) and deoxyguanosine (dG): one with a pseudoequatorial C_1′N₉ glycosyl bond and the other, a slightly more stable one, with its C_1′N₉ bond in a bisectional orientation. In dA, both the N₃ and N₇ nitrogens are plausible sites for electrophilic attack, but only N₇ is a plausible site in dG. The addition of H⁺, CH₃ ⁺, C₂H₅ ⁺ or tert-C₄H₉ ⁺ onto N₇ does not provoke notable structural modifications and leaves the base of dA and dG in an antiperiplanar (or nearly antiperiplanar) position with respect to the sugar C_1′O_4′ bond, but N₃ additions cause the base to adopt a synperiplanar or strongly chiral position. This produces strong interactions between the purine and deoxyribose moieties, whose relief could aid the eventual cleavage of the glycosyl bond of dA. Addition of a radical cation onto N₇ reduces the dissociation energy of the glycosyl bond by an estimated 8 kcal mol⁻¹ in dA and 4 kcal mol⁻¹ in dG – a bond weakening likely to concur to a depurination of DNA induced by radical cations. Received: 13 September 1999 / Accepted: 3 February 2000 / Published online: 21 June 2000     

Spectroscopic study of protonation of oligonucleotides containing adenine and cytosine

Acidobasic properties of purine and pyrimidine bases (adenine, cytosine) and relevant nucleosides (adenosine, cytidine) were studied by means of glass-electrode potentiometry and the respective dissociation constants were determined under given experimental conditions (I = 0.1 M (NaCl), t = (25.0 ± 0.1) °C): adenine (pK _HL = 9.65 ± 0.04, pK _H2L = 4.18 ± 0.04), adenosine (pK _H2L = 3.59 ± 0.05), cytosine (pK _H2L = 4.56 ± 0.01), cytidine (pK _H2L = 4.16 ± 0.02). In addition, thermodynamic parameters for bases: adenine (ΔH ⁰ = (−17 ± 4) kJ mol⁻¹, ΔS ⁰ = (23 ± 13) J K⁻¹ mol⁻¹), cytosine (ΔH ⁰ = (−22 ± 1) kJ mol⁻¹, ΔS ⁰ = (13 ± 5) J K⁻¹ mol⁻¹) were calculated. Acidobasic behavior of oligonucleotides (5′CAC-CAC-CAC3′ = (CAC)₃, 5′AAA-CCC-CCC3′ = A₃C₆, 5′CCC-AAA-CCC3′ = C₃A₃C₃) was studied under the same experimental conditions by molecular absorption spectroscopy. pH-dependent spectral datasets were analyzed by means of advanced chemometric techniques (EFA, MCR-ALS) and the presence of hemiprotonated species concerning (C⁺-C) a non-canonical pair (i-motif) in titled oligonucleotides was proposed in order to explain experimental data obtained according to literature.     

Synthesis and characterization of hyperbranched polyurethane-benzyltetrazole

A series of hyperbranched polyurethane-benzyltetrazoles（H-PBTZs） with different linkage structures were synthesized via the polycondensation of hexamethylenediisocyanate as an A₂ type monomer with（4-（1H-tetrazol-5- yl）benzyl）-diethanolamine（TBDEA） as a BB’₂ type monomer in the absence of catalyst at different temperatures.The FTIR, and ¹³C and ¹H-NMR spectroscopy were used to characterize the molecular structures of TBDEA and H-PBTZs as well as the counterpart linear polyurethane-benzyltetrazole（L-PBTZ）.The molecular composition was determined by the reaction selectivity that the isocyanate group reacted with the hydroxyl group in diethanolamine segment or the active hydrogen atom on tetrazole ring.Raising reaction temperature was propitious to the reaction of isocyanate group with the active hydrogen atom on tetrazole ring.The degrees of branching（DB） for H-PBTZs obtained from the ¹H-NMR spectra increased with raising reaction temperature.The wider molecular weight distribution of 1.7-2.9 for H-PBTZs was obtained via GPC analysis.TGA results showed that H-PBTZs had high thermal stability compared with L-PBTZ.     

Synthesis, charge-separated state characterization of N-methyl-2-(4′-N-ethylcarbozole)-3-fulleropyrrolidine and its derivatives

N-Methyl-2-(N-ethylcarbozole)-fulleropyrro lidine and N-methyl-2-(4′-N,N-diphenylaminophenyl)-fulleropyrrolidine were synthesized by 1,3-dipolar cycloaddition under microwave irradiation, which were characterized by MS, ¹H NMR, IR and UV-Vis. Photoinduced intramolecular electron transfer process from C₆₀ moiety to carbazole moiety has been studied by nanosecond laser flash photolysis. The charge-separated state C₆₀ ^•−-Cz^•+ was observed in the near-IR region with a lifetime of 0.28 μs. The electronic spectrum of the C₆₀-TPA was studied by using ZINDO method on the basis of the optimized geometrics with B3LYP/6-31G* program. The results show that the calculated absorption was beyond 440nm, essentially consistent with the experimental value 433 nm. __________ Translated from Acta Chimica Sinica, 2005,63(17)(in Chinese)     

New pyrrolidine and pyrroline derivatives of fullerenes: from the synthesis to the use in light-converting systems

The results of the authors’ studies on the [2+3] cycloaddition of azomethine and nitrile ylides generated from picolylamine and benzylamine derivatives to fullerenes are systematized and new experimental data are considered. Catalysts and microwave radiation promoting the formation of ylides and their addition to fullerenes were successfully used for the first time. A large series of new pyrrolidine and pyrroline derivatives of fullerenes C₆₀ and C₇₀ were synthesized and characterized. The proposed procedures afford the reaction products in yields twice as high (80–85%) as those attained by the classical Prato reaction. The reactions proceed with virtually complete regio- (in the case of C₇₀) and stereoselectivity to afford only cis-2′,5′-disubstituted and trans-1′,2′,5′-trisubstituted pyrrolidinofullerenes. Pyridyl-substituted pyrrolidinofullerenes react with metalloporphyrins and phthalocyanines to form self-ordered coordination complexes. The latter are analogs of natural photosynthetic antenna systems due to photoinduced charge separation that occurs in these complexes upon exposure to light. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 873–898, May, 2008.     

Ab initio study on the mechanism of cycloaddition reaction between H<Subscript>2</Subscript>Si=Si: and formaldehyde

The mechanism of the cycloaddition reaction between singlet H₂Si=Si: and formaldehyde has been investigated with the CCSD(T)//MP2/6-31G* method. From the potential energy profile, it could be predicted that the reaction has three competitive dominant reaction pathways. The reaction rules presented is that the 3p unoccupied orbital of the Si: atom in H₂Si=Si: inserts the π orbital of formaldehyde from the oxygen side, resulting in the formation of an intermediate. Isomerization of the intermediate further generates a four-membered ring silylene (the H₂Si–O in the opposite position). In addition, the [2+2] cycloaddition reaction of the two π-bonds in H₂Si=Si: and formaldehyde also generates another four-membered ring silylene (the H₂Si–O in the syn-position). Because of the unsaturated property of the Si: atom in the two four-membered ring silylenes, the two four-membered ring silylenes could further react with formaldehyde, generating two silicic bis-heterocyclic compounds. Simultaneously, the ring strain of the four-membered ring silylene (the H₂Si–O in the syn-position) makes it isomerize to a twisted four-membered ring product.     

Synthesis of L-tryptophan labeled with hydrogen isotopes in the indole ring

The isotopomers of L-tryptophan (L-Trp) labeled with hydrogen isotopes in the indole ring were obtained by isotope exchange method. Heavy and tritiated water were used as the sources of stable and radioactive label. Three isotopomers, i.e., [4′-²H]-L-Trp, [4′-³H]-L-Trp, and doubly labeled [4′-²H/³H]-L-Trp were synthesized by isotope exchange enhanced by irradiation with a mercury discharge lamp. The indole whole ring labeled isotopomers, i.e., [2′,4′,5′,6′,7′-²H₅]-L-, [2′,4′,5′,6′,7′-³H₅]-L-, and doubly labeled [2′,4′,5′,6′,7′-²H/³H]-L-Trp were synthesized by isotope exchange between L-Trp and D₂O or DTO in the presence of deuteriated trifluoroacetic acid.     

Cycloaddition of C60 fullerene to stable 2-RSO2-benzonitrile oxides

The interaction of stable 2-RSO₂-benzonitrile oxides1a−c (R=Ph, Bu^t, or PhMeN) with C₆₀ fullerene proceeds at the double (6,6)-bond of fullerene as the [3+2] cycloaddition to form the corresponding isoxazolines2a−c. The molecular structure of compound2b was established by X-ray structural analysis. The interaction of C₆₀ fullerene with 2-(5-methyl-4-nitrothiophene)carbonitrile sulfide, which was obtained by thermolysis of 5-(5′-methyl-4′-nitro-2′-thienyl)1,3,4-oxathiazol-2-one, affords only unstable products. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 118–126, January, 1997.     

Fragmentation of isomeric intrastrand crosslink lesions of DNA in an ion-trap mass spectrometer

The collision-induced dissociation pathways of isomeric cytosine-guanine and cytosine-adenine intrastrand crosslink-containing dinucleoside monophosphates were investigated with the stable isotope-labeled compounds to gain insights into the effects of chemical structure on the fragmentation pathways of these DNA modifications. A Dimroth-like rearrangement, which was reported for protonated 2′-deoxycytidine and involved the switching of the exocyclic N4 with the ring N3 nitrogen atom, was also observed for the cytosine component in the protonated ions of C[5–8]G, C[5–2]A, and C[5–8]A, but not C[5-N ²]G or C[5-N ⁶]A. In these two sets of crosslinks, the C5 of cytosine is covalently bonded with its neighboring purine base via a carbon atom on the aromatic ring and an exocyclic nitrogen atom, respectively. On the contrary, the rearrangement could occur for the deprotonated ions of C[5-N ²]G, C[5-N ⁶]A, and unmodified cytosine, but not C[5–8]G, C[5–2]A, or C[5–8]A. In addition, ammonia could be lost more readily from C[5-N ²]G and C[5-N ⁶]A than from C[5–8]G, C[5–2]A, and C[5–8]A. The results from the present study afforded important guidance for the application of mass spectrometry for the structure elucidation of other intrastrand/interstrand crosslink lesions.     

A bimetallic cyano-bridged complex based on nickel(II) and pentacyanidonitrosylferrate(II) precursors: characterization, crystal structure, and magnetic properties

A heterobimetallic cyano-bridged 1D coordination polymer of the composition [Ni(baepn)(μ-NC)Fe(CN)₃(NO)(μ-CN)]_n·3H₂O has been synthesized by the reaction of nickel(II) nitrate hexahydrate, baepn (baepn = N, N′-bis(2-aminoethyl)-1,3-propanediamine), and sodium nitroprusside dihydrate in a methanol–water mixture. The complex was characterized by physicochemical and spectroscopic methods. The crystal structure was established by single-crystal X-ray diffraction analysis. It reveals cyano-bridged heterometallic chains consisting of alternating arrays of Ni(II) and Fe(II) atoms, both being embedded in distorted octahedral environments. Low-temperature susceptibility measurements show the presence of weak antiferromagnetic exchange interactions between paramagnetic Ni(II) centers (J = −0.46 cm⁻¹) through long diamagnetic [Fe(CN)₅(NO)]²⁻ bridges. Spin state of the iron atom was established by ⁵⁷Fe M?ssbauer spectroscopy.     

Crystal and molecular structure studies of 1′-Benzyl-8-(4-fluorobenzyl)-8-azaspiro[bicyclo-[3.2.1]octane-3,4′-imidazolidine]-2′,5′-dione

The title compound 1′-Benzyl-8-(4-fluorobenzyl)-8-azaspiro[bicyclo[3.2.1] octane-3,4′-imidazolidine]-2′,5′-dione, C₂₃H₂₃FN₃O₂ is synthesized and the structure is investigated by X-ray diffraction studies. The compound crystallizes in the triclinic crystal class in the P1 space group. The hydantoin ring adopts a planar conformation and is affected by the π conjugation. The pyrrolidine and piperidine rings in the bicyclo octane moiety adopt envelope and chair conformations respectively. The structure exhibits both inter- and intramolecular hydrogen bonds of the type N-H...O, C-H...O, and C-H...N. The oxygen atom in the hydantoin ring simultaneously accepts two hydrogen bonds to form a three-centered hydrogen bonding pattern.     

Enzymatic synthesis of dopamine ring labeled with hydrogen isotopes

The synthesis of two isotopomers of L-DOPA, the precursors for labeled dopamine is reported. The ring labeled with deuterium or tritium [2′,5′,6-²H₃]-L-DOPA, and [2′,5′,6-³H₃]-L-DOPA were obtained using acid catalyzed isotopic exchange between L-DOPA and heavy or tritiated water, respectively. Their derivatives, i.e., [2′,5′,6-²H₃], and [2′,5′,6-³H₃]-dopamine were obtained by enzymatic decarboxylation of deuterated or tritiated isotopomers of L-DOPA using enzyme tyrosine decarboxylase (EC 4.1.1.25).     

Synthesis and comparative X-ray diffraction study of first ruthenocene-based pincer palladium complexes, PdCl[{2,5-(But 2PCH2)2C5H2}Ru(Cp′)] (Cp′ = C5H5 or C5Me5)

First ruthenocene-based palladium complexes PdCl[{2,5-(Bu^t ₂PCH₂)₂C₅H₂} Ru(Cp′)] (Cp′ = C₅H₅ (4) or C₅Me₅ (5)) were synthesized. Comparative single-crystal X-ray diffraction study of complexes 4 and 5 showed that the deviations of the cyclopentadienyl rings in these complexes from being parallel are 2.6 and 10.1°, respectively. In addition, the shift of the palladium atom relative to the plane of the metallated cyclopentadienyl ligand is 0.007 Å for 4 and 0.336 Å for 5. These differences in the structures of complexes 4 and 5 are due to close contacts between the pseudoequatorial tert-butyl groups at the phosphorus atoms and the unmetallated cyclopentadienyl ring. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 1879–1884, November, 2006.     

Mixed-ligand iridium(IV) complexes with amino acids,adenine and hypoxanthine

The complexation in iridium(IV)-purine base (adenine, hypoxanthine)-amino acid (α-alanine, aspartic acid, lysine) systems was studied by pH titration. The stability constants of 1: 1: 1 complexes were determined. The stability of 1: 1: 1 mixed-ligand complexes with hypoxanthine and adenine increases in the series Ala < Lys < Asp. Reactions between aqueous solutions gave the following coordination compounds: [Ir(C₅H₄N₄O)(C₃H₆NO₂)Cl]Cl₂, [Ir(C₅H₄N₄O)(C₄H₅NO₄)]Cl₂, [Ir(C₅H₄N₄O)(C₆H₁₃N₂O₂)]Cl₃, [Ir(C₅H₅N₅)(C₃H₆NO₂)]Cl₃, [Ir(C₅H₅N₅)(C₄H₅NO₄)]C_l2, and [Ir(C₅H₅N₅)(C₆H₁₃N₂O₂)]Cl₃. The individual character of the complexes was established by chemical and thermogravimetric analyses and powder X-ray diffraction. The complexes were characterized by NMR, IR, and X-ray photoelectron spectroscopy. Alanine and lysine in mixed-ligand iridium(IV) complexes are bidentate (α-NH₂ and COO⁻ groups), aspartic acid is tridentate, and purine bases function as polydentate ligands through heterocycle N atoms and functional groups (NH₂ in adenine and C=O in hypoxanthine).     

Dimerization of cyclopentadienyl ligands in the synthesis of transition metal complexes. 1,4,5,6,7,10,11,12-Octamethyltricyclo[7.3.0.03,7]-dodeca-3,5,9,11-tetraene and the complex of 1,1′,3,3′-tetrakis-(tert-butyl)-1,1′-dihydrofulvalene with I3 −

1,4,5,6,7,10,11,12-Octamethyltricyclo[7.3.0.0^3,7]dodeca-3,5,9,11-tetraene was obtained as a by-product in the synthesis of (C₅Me₅)₂CeCl from CeCl₃ and NaC₅Me₅. The complex of 1,1′,3,3′-tetrakis(tert-butyl)-1,1′-dihydrofulvalene with I₃ ⁻ was obtained as the major product in the reaction of YbI₃ with 1,3-Bu^t ₂C₅H₃Na. The structures of the title compounds were established by X-ray diffraction analysis. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2310–2314, December, 1999.     

Spatial structure of β-cyclodextrin clathrates with 1,4-benzodiazepine derivatives

Understanding the mechanisms of mutual recognition and complementary binding of molecules in guest-host complexes is based on analysis of their spatial structure. As guest-host complexes, we have synthesized inclusion compounds of 1,4-benzodiazepine anxiolytic agents gidazepam and cinazepam with β-cyclodextrin, in which these anxiolytic agents manifest increased biological accessibility. The spatial structure of the complexes was determined from the two-dimensional NOESY spectra and analysis of the fragmentary mobility of the guest and host molecules, characterized by spin-lattice relaxation times T₁ of the¹³C nuclei. An analysis of d-contacts showed that the 5-phenyl ring is completely enclosed in the inner hydrophobic cavity of β-CD [(C^2′ H-C^4′ H)-CIIH(CIVH), CVH (CIIIH, CVIH₂), CVIOH]. For the 1:1 complex, intense d-contracts of C⁸H with CVIOH indicate that C⁸H is located in the vicinity of both wide and narrow bases of the bracelet. This is only possible for the 2:2 complex, in which both β-CD molecules approach each other by their wide and narrow bases. A comparison between the schemes of d-contacts for the 2:2 and 2:1 associates proves that the β-CD molecules have the same spatial orientation in the dimer. The difference is in the fact that the hydrazinocarbonyl fragment of gidazepam and the hemisuccinate fragment of cinazepam penetrate into an empty molecule of the 2:1 β-CD complex (NH₂-CIH contact). The intensities of the cross peaks were measured, due to which the interatomic distances between the guest and host molecules were calculated and the spatial structure of the clathrates was established. The benzodiazepine derivatives are embedded differently into the clathrate molecule, as shown by the value of the angle between the symmetry axis of β-CD and the axis through the centers of the aromatic rings: 0° for gidazepam and 60° for cinazepam. This is a consequence of the fact that the substituents forming hydrogen bonds with hydroxyl groups at the wide base of the β-CD bracelet lie in different positions: the hydrazinocarbonylmethyl fragment of gidazepam lies at N¹, and the hemisuccinate fragment of cinazepam is at C³. A. V. Bogatskii Physicochemical Institute, Ukrainian National Academy of Sciences. Translated fromZhurnal Strukturnoi Khimii, Vol. 37, No. 5, pp. 876–890, September–October, 1996. Translated by L. Smolina     

Ab initio study of mechanism of forming a spiro-heterocyclic ring compound involving Si from dichlorosilylenesilylene (Cl2Si=Si:)→Cl2Si=Si: and aldehyde

The mechanism of the cycloaddition reaction between singlet dichlorosilylenesilylene (Cl₂Si=Si:)→Cl₂Si=Si: and aldehyde has been investigated with the CCSD(T)//MP2/6-31G* method. From the potential energy profile, it could be predicted that the reaction has one dominant reaction pathway. The reaction rules presented is that the two reactants firstly form a four-membered ring silylene through the [2+2] cycloaddition reaction. Because of the 3p unoccupied orbital of Si: atom in the four-membered ring silylene and the π orbital of aldehyde forming a π → p donor–acceptor bond, the four-membered ring silylene further combines with aldehyde to form an intermediate. Because the Si: atom in the intermediate happens sp ³ hybridization after transition state, then the intermediate isomerizes to a spiro-heterocyclic ring compound involving Si via a transition state.     

Some condensations of methyl 4-acetylphenylcarbamate

Condensation of methyl 4-acetylphenylcarbamate with isatin in the presence of diethylamine afforded methyl 4-[(3-hydroxy-2-oxo-2,3-dihydro-1H-indol-3-yl)acetyl]phenylcarbamate which was converted into the corresponding chalcone on heating in glacial acetic acid in the presence of hydrochloric acid. 1,3-Dipolar cycloaddition to that chalcone of azomethine ylide generated from 2-phenacylisoquinolinium bromide by the action of triethylamine gave methyl 4-(3′-benzoyl-2-oxo-1′,2,2′,3,3′,10b′-hexahydro-1H-spiro-[indole-3,1′-pyrrolo[1,2-a]isoquinolin]-2′-ylcarbonyl)phenylcarbamate. Condensation of 2-hydroxy- and 2,4-dihydroxybenzaldehydes with methyl 4-acetylphenylcarbamate in the presence of gaseous hydrogen chloride resulted in the formation of chromenium salts with a methoxycarbonylaminophenyl fragment on the C² atom in the heteroring.     

Ab initio Study on Formation Mechanism of Spiro-Si-Heterocyclic Ring Compound Involving Ge from H2Ge=Si: and Formaldehyde

H₂Ge=Si: and its derivatives (X₂Ge=Si:, X=H, Me, F, Cl, Br, Ph, Ar,…) are new species. Its cycloaddition reactions are new area for the study of silylene chemistry. The cycloaddition reaction mechanism of singlet H₂Ge=Si: and formaldehyde has been investigated with the MP2/aug-cc-pVDZ method. From the potential energy profile, it could be predicted that the reaction has one dominant reaction pathway. The reaction rule is that two reactants firstly form a four-membered Ge-heterocyclic ring silylene through the [2+2] cycloaddition reaction. Because of the 3p unoccupied orbital of Si: atom in the four-membered Ge-heterocyclic ring silylene and the π orbital of formaldehyde forming a π→p donor-acceptor bond, the four-membered Ge-heterocyclic ring silylene further combines with formaldehyde to form an intermediate. Because the Si: atom in the intermediate undergoes sp³ hybridization after transition state, then the intermediate isomerizes to a spiro-Si-heterocyclic ring compound involving Ge via a transition state. The result indicates the laws of cycloaddition reaction between H₂Ge=Si: or its derivatives (X₂Ge=Si:, X=H, Me, F, Cl, Br, Ph, Ar,…) and asymmetric π-bonded compounds are significant for the synthesis of small-ring involving Si and Ge and spiro-Si-heterocyclic ring compounds involving Ge.