Crystal structure and physical properties of the new 2D polymeric compound bis(1,5-diaminotetrazole)dichlorocopper(II)

Two new coordination complexes, Cu(datz)Cl₂ and Cu(datz)₂Cl₂, where datz is 1,5-diaminotetrazole, have been obtained by the reaction of copper(II) chloride with datz. For one of them, Cu(datz)₂Cl₂, the crystal structure, magnetic susceptibility and thermal properties are reported. For the other compound only spectroscopic and thermal properties are presented. In Cu(datz)₂Cl₂ the Cu atoms were found to be octahedrally coordinated. Equatorial positions are occupied by two chloride anions and two tetrazole ligands via their N⁴ donor atoms. Surprisingly, the amino groups at the N¹ atom of the tetrazole ring of nearby molecules are in axial positions. Each copper atom is linked with four others through the datz molecules to form 2D polymeric networks parallel to the yz plane. Magnetic properties of Cu(datz)₂Cl₂ and the data of quantum-chemical calculations of molecular electrostatic potential and energies of hydronation of nitrogen atoms for datz using MP2/6-31G* and B3LYP/6-31G* levels of theory are in agreement with the structural data obtained.     

A New Synthesis Of Coenzymically Active Water-Soluble Macromolecular Nad And Nadp Derivatives

Based on an unexpected transformation of N (1)-(2-aminoethyl)-NAD(P) to N⁶-(2-aminoethy1)-NAD(P) under mild aqueous conditions (pH 6.0-6.5, 50°C) synthesis of uniform macromolecular derivatives of N⁶-alkylated NAD and N⁶-alkylated NADP was possible, with, in most cases, acceptable overall yields (6-37%). The usual steps of (a) the chemical reduction with Na₂S₂O₄,(b) the Dimroth rearrangement under harsh alkaline conditions and (c) the enzymatic or chemical oxidation were omitted. This represents a significant simplification of the procedure. A common procedure for the synthesis of macromolecular N⁶-(2-aminoethyl)-NAD(P) derivatives was pursued, coupling N⁶-(2-aminoethyl)-NAD(P) to several water-soluble copolymers containing maleic acid anhydride. PEG (M_r = 20000)-N⁶-(2-aminoethl)-NAD, polyvinylpyrrolidone (M_r,= 160000)-N⁶-(2-aminoethylNAD and dextran (M_r= 70000)-N⁶-(2-aminoethyl)-NAD were synthesized by covalently binding N⁶-(2-aminoethyl)-NAD to the corresponding carboxylated polymers by the carbodiimide method. PEG (M_r= 4000 and 20000-N⁶-(2-aminoethyl)-NADP was efficiently synthesized by covalent attachment of N⁶-(2-aminoethyl)-NADP to N-hydroxy-succinimide activated carboxylate PEG (M_r= 4000 and 20000), avoiding the carbodiimide method, which would lead simultaneously to 2′3′-cyclic NADP derivatives. Except for the macromolecular cofactor derivatives based on copolymers containing maleic acid anhydride, the total enzymatic reducibility of the macromolecular N-(2-aminoethyl)-NAD(P) derivatives was satisfactory (90-95%).     

The synthesis and biological properties of 8-azido-N 6-benzyladenine,a potential photoaffinity reagent for cytokinin

A cytokinin photoaffinity reagent, 8-azido-N ⁶-benzyladenine (8N₃BA), was synthesized from 8-bromoadenosine via azide replacement, benzylation at N–1, rearrangement to the N-6-benzyl derivative and acid hydrolysis. The compound thus obtained was found to have full cytokinin activity in the moss and tobacco cell-suspension bioassays. Photolysis of 8N₃BA was accomplished with long and short-wavelength ultraviolet light and produced compounds which had very little or no biological activity in the two bioassays. In-vivo photolysis of 8N₃BA caused loss of the cytokinin activity of this compound in moss protonemata. This result was similar to earlier ones where the biological response of moss protonemata to benzyladenine was reversed following removal of the hormone by a short rinse with water.Abbreviations BA N ⁶-benzyladenine - 8N₃BA 8-azido-N ⁶-benzyladenine - PMR proton magnetic resonance - TLC thin-layer chromatography - UV ultraviolet In partial fulfillment of requirements for the Ph.D. degree at Michigan State University     

Theoretical study of N<Subscript>4</Subscript>X (X = O,S, Se) systems

A series of N₄X (X = O, S, Se) compounds have been examined with ab initio and density functional theory (DFT) methods. To our knowledge, these compounds, except for the C_2v ring and the C_3v towerlike isomers of N₄O, are first reported here. The ring structures are the most energetically favored for N₄X (X = O and S) systems. For N₄Se, the cagelike structure is the most energetically favored. Several decomposition and isomerization pathways for the N₄X species have been investigated. The dissociation of C_2v ring N₄O and N₄S structures via ring breaking and the barrier height are only 1.1 and −0.2 kcal mol⁻¹ at the CCSD(T)/6-311+G*//MP2/6-311+G* level of theory. The dissociation of the cagelike N₄X species is at a cost of 12.1–16.2 kcal mol⁻¹. As for the towerlike and triangle bipyramidal isomers, their decomposition or isomerization barrier heights are all lower than 10.0 kcal mol⁻¹. Although the C_S cagelike N₄S isomer has a moderate isomerization barrier (18.3–29.1 kcal mol⁻¹), the low dissociation barrier (−1.0 kcal mol⁻¹) indicates that it will disappear when going to the higher CCSD(T) level. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Nucleotide-induced conformations of myosin: A comparison of states formed with MgϵADP and MgADP

Previous work has shown that modification of the 1 and 6 positions of the adenosine ring of ADP by forming the 1,N⁶-etheno derivative does not alter the binding affinity of the nucleotide to myosin. The data presented in this communication indicate that despite the identity of binding parameters the interaction between the modified nucleotide and myosin is not the same as that occurring with MgADP. Alkylation studies indicate that the SH₁ thiol is more accessible in the myosin-Mg?ADP complex whereas the SH₂ thiol is less accessible compared to their reactivities in the myosin-MgADP state. Studies with the bifunctional reagent p-phenylenedimaleimide indicate that these thiols are also further apart in the protein-modified nueleotide complex. These studies suggest that ring 1 of the adenosine nucleotide diphosphate is implicated in the interaction that exposes the SH₂ site to alkylation.     

Biosynthetic relations between protoberberine-, benzo(C)phenanthridine- and B-secoprotoberberine type alkaloids in Corydalis incisa

The biosynthetic relations between protoberberine-, benzo[C]phenanthridine- and B-secoprotoberberine type alkaloids were demonstrated by use of (±)-tetrahydrocoptisine-[8,14-³H HCl, (±)-tetrahydrocorysamine-[8,14-³H]HCl and corynoline-[6-³H]HCl in Corydalis incisa, and the following results were presented. (±)-Tetrahydrocoptisine was converted to corynoline, corydalic acid methyl ester and corydamine hydrochloride. (±)-Tetrahydrocorysamine was converted to corynoline and corydalic acid methyl ester. Evidence that N-methyl-3-[6′-(3′,4′-methylenedioxyphenethylalcohol)]-4-methyl-7,8-methylenedioxy-1,2,3,4-tetrahydroisoquinoline-[α-³H] HCl was incorporated into corynoline-[11-³H] indicates the occurrence of the ring fission at C₆-N followed by linking ofthe C₆ and C₁₃ positions in (±)-tetrahydrocoptisine and (±)-tetrahydrocorysamine, and suggests the participation of one of two possible intermediates in the biosynthesis of these alkaloids.     

Kinetic and thermodynamic study of the substituent effect on the amino-Claisen rearrangement of para-substituted N-allyl-N-arylamine: a Hammett study via DFT

In order to find the susceptibility of the amino-Claisen rearrangement and the next proton shift reaction of N-allyl-N-arylamine to the substituent effects in the para position, the kinetic and thermodynamic parameters were calculated at the B3LYP level using the 6-31G^** basis set. The calculated activation energies for the rearrangements and proton shift reactions are close to 44.4 and 49.5 kcal mol^? 1, respectively. The transition states of the rearrangement with electron-donor substituents are more stable than those with electron-withdrawing substituent groups, but for the proton shift reaction, this situation is reversed (with the exception of fluorine atom for the rearrangement and fluorine and chlorine atoms for the proton shift reaction). Negative values for the activation entropy confirm the concerted mechanism for the amino-Claisen rearrangement and proton shift reaction. The Hammett ρ values of ? 2.4172 and ? 1.7791 are obtained for σ_p and σ^?  (enhanced sigma) in the amino-Claisen rearrangement, respectively. The correlation between log(k _X/k _H) and σ_p is weaker than that with σ^?  (enhanced sigma). A negative Hammett ρ value indicates that the electron-donating groups slightly increase the rate of amino-Claisen rearrangement. A positive Hammett ρ value (2.4921) for the proton shift reaction indicates that electron-withdrawing groups increase the rate of reaction.     

Synthesis,anticancer activity,and SAR analyses of compounds containing the 5:7-fused 4,6,8-triaminoimidazo[4,5-e][1,3]diazepine ring system

Described herein are our limited structure–activity relationship (SAR) studies on a 5:7-fused heterocycle (1), containing the 4,6,8-triaminoimidazo[4,5-e][1,3]diazepine ring system, whose synthesis and potent broad-spectrum anticancer activity we reported a few years ago. Our SAR efforts in this study are mainly focused on judicial attachment of substituents at N-1 and N⁶-positions of the heterocyclic ring. Our results suggest that there is some subtle correlation between the substituents attached at the N-1 position and those attached at the N⁶-position of the heterocycle. It is likely that there is a common hydrophobic binding pocket on the target protein that is occupied by the substituents attached at the N-1 and N⁶-positions of the heterocyclic ligand. This pocket appears to be large enough to hold either a C-18 alkyl chain of N⁶ and no attachment at N-1, or a combined C-10 at N⁶ and a CH₂Ph at N-1. Any alkyl chain shorter or longer than C-10 at N⁶ with a CH₂Ph attached at N-1, would result in decrease of biological activity.     

A Functional Screening of Adenosine Analogues at the Adenosine A2B Receptor: A Search for Potent Agonists

Abstract

Various adenosine analogues were tested at the adenosine A_2B receptor. Agonist potencies were determined by measuring the cyclic AMP production in Chinese Hamster Ovary cells expressing human A_2B receptors. 5′-.N-Substituted carboxamidoadenosines were most potent. 5′-N-Ethylcarboxamidoadenosine (NECA) was most active with an ECso value of 3.1 μM. Other ribose modified derivatives displayed low to negligible activity. Potency was reduced by substitution on the exocyclic amino function (N⁶) of the purine ring system. The most active N⁶-substituted derivative N⁶-methyl-NECA was 5 fold less potent than NECA. C8-and most C2-substituted analogues were virtually inactive. 1-Deaza-analogues had a reduced potency, 3-and 7-deazaanalogues were not active.     

Synthesis of N-phenyl-N-(3-(piperidin-1-yl)propyl)benzofuran-2-carboxamides as new selective ligands for sigma receptors

Novel benzofuran-2-carboxamide ligands, which are selective for sigma receptors, have been synthesized via a microwave-assisted Perkin rearrangement reaction and a modified Finkelstein halogen-exchange used to facilitate N-alkylation. The ligands synthesized are the 3-methyl-N-phenyl-N-(3-(piperidin-1-yl)propyl)benzofuran-2-carboxamides (KSCM-1, KSCM-5 and KSCM-11). The benzofuran-2-carboxamide structure was N-arylated and N-alkylated to include both N-phenyl and N-(3-(piperidin-1-yl)propyl substituents, respectively. These new carboxamides exhibit high affinity at the sigma-1 receptor with K_i values ranging from 7.8 to 34 nM. Ligand KSCM-1 with two methoxy substituents at C-5 and C-6 of the benzofuran ring, and K_i = 27.5 nM at sigma-1 was found to be more selective for sigma-1 over sigma-2.     

Absolute stereochemistry of methanopterin and 5,6,7,8-tetrahydromethanopterin

The configuration at the C-9 of methanopterin (MPT) has been determined by comparing the circular dichroism (CD) spectra of MPT and its hydrolytic fragment, 1-[4-[[1-(2-amino-7-methyl-4-hydroxy-6-pteridinyl)-ethyl]amino]phenyl]-1-deoxy-D -ribitol (HP-1), with the CD spectra of a series of model compounds of known stereochemistry. These compounds included (S)-6-[1-(4-carboxymethylanilino)ethyl]pterin, (S-6(1-hydroxyethyl)-7-methylpterin, (S-6-(1-hydroxyethyl)pterin, (R)-6-(1-phenoxyethyl)pterin, D (+)-neopterin, and L -biopterin. From this comparison it was concluded that MPT has the R configuration at C-9 and is thus configurationally related to D (+)-neopterin, which has the S configuration at C-1. From previous work establishing the relative stereochemistry at C-6, C-7, and C-9 of N⁵-N¹⁰-methenyl-5,6,7,8-tetrahydromethanopterin (N⁵-N¹⁰-methenyl-H₄MPT) as R, S, and R, respectively, it is clear that the remaining asymmetric carbons at C-6 and C-7 of H₄MPT have the S and S configuration, respectively. Comparison of these latter two positions to the equivalent carbons in 5,6,7,8-tetrahydrofolate (H₄folate) show that the steps involved in the biological reduction of MPT to H₄MPT occur with the same stereochemical outcome as those involved in the biological reduction of folate to H₄folate. © 1996 Wiley-Liss, Inc.     

The cleavage of cyclopentadienyl substituted η6-arene η5-cyclopentadienyl iron(II) cations by phospholyl anions. A facile route to 1′-substituted monophosphaferrocenes

η⁶-Arene η⁵-cyclopentadienyl iron PF₆⁻ salts bearing substituents on the cyclopentadienyl ring are cleaved by phosphacyclopentadienyl anions (PCp⁻ M⁺) to give 1′-substituted monophosphaferrocenes. Such derivatives are unavailable via chemical modification of monophosphaferrocenes such as Friedel-Crafts reaction or metallation, l′-Alkyl, acyl, N,N-dimethylaminomethyl and l′-carboxylic acids have been synthesised and characterised. Nucleophilic displacement of chloride by PCp⁻M⁺ in the η⁶-chlorobenzene cation produces novel 1- phenylphospholes one of which has been isolated and characterised. The synthetic route was found to be unsuccessful in the production of azaferrocene.     

Synthesis, crystal structure and magnetic properties of a novel iron(III) 18-azametallacrown-6 compound

A novel macrocyclic hexanuclear iron(III) 18-azametallacrown-6 compound, [Fe₆(C₉H₇N₂O₃)₆(CH₃OH)₆]·8CH₃OH·2H₂O, has been prepared using a trianionic pentadentate ligand N-acetylsalicylhydrazide (ashz³⁻) and characterized by X-ray diffraction. Due to the meridional coordination of the ligand to the Fe³⁺ ion, the ligand enforces the stereochemistry of the Fe³⁺ ions as a propeller configuration with alternating Λ/Δ forms. The disc-shaped hexanuclear ring shows about 6.20 Å in diameter at entrance, about 9.31 Å at its largest diameter at the center of the cavity, respectively. There are many kinds of intramolecular and intermolecular hydrogen bonds in the title compound. The OH?O hydrogen bond distances range from 2.609(5)-2.901(5) Å. The magnetic susceptibility (4-275K) study indicates antiferromagnetic exchange interactions between the adjacent Fe³⁺ ions around the ring.     

Structures and stability of N<Subscript>13</Subscript><Superscript>+</Superscript> and N<Subscript>13</Subscript><Superscript>−</Superscript> clusters

The structures and stabilities of eleven N₁₃ ⁺ and N₁₃ ^– isomers have been investigated with second-order Møller–Plesset (MP2) and density functional theory (DFT) methods. Five N₁₃ ⁺ isomers and six N₁₃ ^– isomers are all reasonable local minima on their potential energy hypersurfaces. The most stable N₁₃ ⁺ cation is structure C-2 with C_2v symmetry, which contains a pentazole ring and two N₄ open chains. It is different from those of the N₇ ⁺ and N₉ ⁺ clusters, but similar to the N₁₁ ⁺ cluster. Meanwhile, the most stable N₁₃ ^– structure A-2 is composed of a pentazole ring and a six-membered ring connected by two nitrogen atoms. It is not only different from those of the N₇ ^– and N₉ ^– clusters, but also from the N₁₁ ^– cluster. The decomposition pathways of structures C-2 and A-2 were investigated at the B3LYP/(aug)-cc-pVDZ level. From the barrier heights of the structures C-2 and A-2 decomposition processes, it is suggested that C-2 is difficult to observe experimentally and A-2 may be observed as a short-lived species. Figure Optimized geometrical parameters of N₁₃ ⁺ isomer C-2      

Synthesis, characterization and X-ray crystal structure of [Re(L4)(CO)3]Br · 2CH3OH (L4 = N,N-bis[(2-diphenylphosphino)ethyl]methoxyethylamine): A model compound for novel cationic Tc(I)-tricarbonyl radiotracers useful for heart imaging

This report describes synthesis and evaluation of cationic complexes, [^99mTc(CO)₃(L)]⁺ (L = N-methoxyethyl-N,N-bis[2-(bis(3-ethoxypropyl)phosphino)ethyl]amine (L1), N-[(15-crown-5)-2-yl]-N,N-bis[2-(bis(3-ethoxypropyl)phosphino)ethyl]amine (L2) and N-[(18-crown-6)-2-yl]-N,N-bis[2-(bis(3-ethoxypropyl)phosphino)ethyl]amine (L3)) as potential radiotracers for heart imaging. Preliminary results from biodistribution studies in female adult BALB-c mice indicated that the cationic ^99mTc(I)-tricarbonyl complex, [^99mTc(CO)₃(L2)]⁺, has a significant localization in the heart at 60 min post-injection. To understand the coordination chemistry of these bisphosphine ligands with the ^99mTc(I)-tricarbonyl core, we prepared [Re(CO)₃(L4)]Br (L4: N,N-bis[(2-diphenylphosphino)ethyl]methoxyethylamine) as a model compound. [Re(CO)₃(L4)]Br has been characterized by elemental analysis, IR, ESI-MS, NMR (¹H, ¹³C, ¹H-¹H COSY, and ¹H-¹³C HMQC) methods, and X-ray crystallography. In solid state, [Re(CO)₃(L4)]⁺ has a distorted octahedron coordination geometry with PNP occupying one facial plane. The chelator backbone adopts a “chair” conformation with phosphine-P atoms at equatorial positions and the amine-N at the apical site. In solution, [Re(CO)₃(L4)]⁺ is able to maintain its cationic nature with no dissociation of carbonyl ligands or any of the three PNP donors.     

Preparation and crystal structure of the hydroxo-bridged complex biscyclo-tri-μ-hydroxo-tris[(trans-1,2-diaminocyclohexane)platinum(II)] tris

The title compound, [C₁₈H₄₅N₆O₃Pt₃]2(SO₄)₃·14H₂O, belongs to space group C2/c, with a = 25.90(2) Å, b = 14.33(2) Å, c = 23.74(3) Å, β = 122.88(7)°, and Z = 4. The structure was refined on 2899 independent nonzero reflections to an R factor of 0.042. The crystal contains hydroxobridged cyclic [Pt₃(OH)₃(C₆H₁₄N₂)₃]³⁺ ions, in which the Pt₃O₃, ring has a chair conformation. The coordination around each Pt atom is square planar and the cyclohexyl ring lies roughly in the same plane. A large cavity between two trimeric ions related by a twofold axis is filled with one SO₄^2- ion and five water molecules, which participate in an intricate network of hydrogen bonds among themselves and with the hydroxo and amino groups of the complex cation. These units are held together in the crystal by stacking interactions between Pt(OH)₂(C₆H₁₄N₂) “planes” belonging to adjacent molecules, as well as by hydrogen bonds involving the remaining SO₄^2- ions and water molecules. The presence of the cyclohexane ring precludes λ-δ interconversion in the chelate ring and imparts rigidity to the Pt(trans-dach)²⁺ unit.     

The structural and electrochemical consequences of hydrogenating copper N2S2 Schiff base macrocycles

A series of cis and trans tetradentate copper macrocyclic complexes, of ring size 14-16, that employ amine and thioether donor groups are reported. Apart from 5,6,15,16-bisbenzo-8,13-diaza-1,4-dithia-cyclohexadecane copper(I) (cis-[Cu(H₄N_buS_en)]⁺) all of the complexes are obtained in the copper(II) form. Crystallographic analysis shows that the copper(II) complexes all adopt a distorted planar geometry around the copper. In contrast, cis-[Cu(H₄N_buS_en)]⁺ is found to adopt a distorted tetrahedral geometry. The complexes were subjected to electrochemical analysis in water and acetonitrile. The effect of the solvent, positions of the donor atoms (cis/trans) on E^1/2 is discussed as is the comparison of the electrochemical behaviour of these complexes with their parent Schiff base macrocycles.     

C-A base pairs in transfer ribonucleic acids and codon-anticodon complexes

Two hundred and thirty three nucleotide sequences of tRNAs were investigated to elucidate the frequency of appearance of C-A (cytosine-adenine) pairs in their main two-stranded regions, in the positions 26–44 and 15–48². It was supposed that in the formation of C-A pairs on antiparallel polynucleotide chains the atomic groups -N₄H and -N₃ of cytosine make up Hbonds with the groups N₇- and HN₆- of adenine. On parallel chains, Hbonds, probably, form -N₆H and -N₁ groups of adenine with N₃- and HN₄- of cytosine. The calculation results predicted a significant energy of interaction between cytosine and adenine. By the investigation of the molecular models it was shown that the formation of Hbonded C-A pairs requires considerable changes of conformation in ribose-phosphate chains. In addition, a theoretical analysis revealed the possibility of formation of C-A pairs at the wobble-position of the codon-anticodon complex. The significance of this nucleotide pair in the processes of genetic coding proved to depend on the stability of the codon-anticodon complex, the modification of cytosine 34 and structural features of the distant regions of the tRNA.     

Comparative theoretical study of the UV/Vis absorption spectra of styrylpyridine compounds using TD-DFT calculations

This study examined absorption properties of 2-styrylpyridine, trans-2-(m-cyanostyryl)pyridine, trans-2-[3-methyl-(m-cyanostyryl)]pyridine, and trans-4-(m-cyanostyryl)pyridine compounds based on theoretical UV/Vis spectra, with comparisons between time-dependent density functional theory (TD-DFT) using B3LYP, PBE0, and LC-ωPBE functionals. Basis sets 6–31G(d), 6–31G(d,p), 6–31+G(d,p), and 6–311+G(d,p) were tested to compare molecular orbital energy values, gap energies, and maxima absorption wavelengths. UV/Vis spectra were calculated from fully optimized geometry in B3LYP/6–311+G(d,p) in gas phase and using the IEFPCM model. B3LYP/6–311+G(d,p) provided the most stable form, a planar structure with parameters close to 2-styrylpyridine X-ray data. Isomeric structures were evaluated by full geometry optimization using the same theory level. Similar energetic values were found: ～4.5 kJ?mol^?1 for 2-styrylpyridine and ～1 kJ?mol^?1 for derivative compound isomers. The 2-styrylpyridine isomeric structure differed at the pyridine group N-atom position; structures considered for the other compounds had the cyano group attached to the phenyl ring m-position equivalent. The energy difference was almost negligible between m-cyano-substituted molecules, but high energy barriers existed for cyano-substituted phenyl ring torsion. TD-DFT appeared to be robust and accurate approach. The B3LYP functional with the 6–31G(d) basis set produced the most reliable λ_max values, with mean errors of 0.5 and 12 nm respect to experimental values, in gas and solution, respectively. The present data describes effects on the λ_max changes in the UV/Vis absorption spectra of the electron acceptor cyano substituent on the phenyl ring, the electron donor methyl substituent, and the N-atom position on the electron acceptor pyridine ring, causing slight changes respect to the 2-styrylpyridine title compound.