Linear Tetraamines Research Articles

Synthesis and Characterization of Bis-quinazolines from Linear Tetra-amines Involving 2-(Aminomethyl)benzenamine with Aldehydes

Three tetra‐amine compounds 2‐((2‐(2‐aminobenzylamino)ethylamino)methyl)benzenamine (L1), 2‐((3‐(2‐aminobenzylamino)propylamino)methyl)benzenamine (L2), and 2‐((4‐(2‐aminobenzylamino) butylamino)methyl)benzenamine (L3) were synthesized and then their reaction with 2‐hydroxybenzaldehyde, 2‐nitrobenzaldehyde, and 2‐hydroxy‐3‐methoxybenzaldehyde were investigated. Treatment of L1 ,L 2 ,a nd L3 with the former aldehydes gave derivatives of quinazolines in a good yield. The products have been studied with IR, 1 HN MR, 13 C NMR, COSY, HMQC, and microanalysis.

Glyphosate and ATP binding by mononuclear Zn(ii) complexes with non-symmetric ditopic polyamine ligands

Binding of Zn(II) by the ditopic ligands L1py, L2py and L1para, composed of a cyclam unit linked to the linear polyamines 1,4,8,11-tetraazaundecane (L1py and L2para) and 1,4,7-triazaheptane (L2py) via a 2,6-dimethylpyridinyl (L1py and L2py) or a 1,4-dimethylbenzyl spacer (L2para), has been analyzed by means of potentiometric and (1)H and (13)C NMR measurements. All ligands form stable mononuclear Zn(II) complexes in a wide pH range, featuring the metal ion bound to the macrocyclic unit. The open-chain polyamine unit can easily bind several protons in aqueous solution affording protonated metal complexes at neutral and acidic pH values. These complexes behave as bifunctional receptors for the anionic substrates N-(phosphonomethyl)glycine (glyphosate or PMG) and ATP. Potentiometric, (1)H and (31)P NMR measurements show that the Zn(II) complex with L1py is the better receptor for both substrates, thanks to the simultaneous presence of a pyridine linker functionalized at its 2,6 positions and of a flexible linear tetraamine chain. In fact, these structural features allow a stronger interaction of PMG and ATP with both the protonated tetraamine moiety and the Zn(II)-cyclam core.

Selective Binding of Glyphosate by a Ditopic Cyclic–Open‐Chain Polyazaligand in Aqueous Solution

AbstractThis paper reports a study of the interaction between a ditopic cyclic–open‐chain polyazaligand L1py and the herbicide glyphosate [N‐(phosphonomethyl)glycine or PMG] by potentiometric titrations as well as calorimetry and NMR measurements. This nonsymmetrical ligand is composed of a cyclam unit (1,4,8,11‐tetraazacyclotetradecane) and the linear tetraamine 1,4,8,11‐tetraazaundecane linked by a 2,6‐dimethylpyridine spacer. This ligand forms stable adducts with PMG. For comparison, two analogous symmetrical ditopic ligands, a bis‐macrocycle L4py and a bis‐tetraamine L5py, and two related anions, iminodiacetic acid (IDA) and iminobis(methylphosphonic acid) (IDP), were also investigated. The results unambiguously show that L1py selectively binds PMG, especially around neutral pH, whereas L4py and L5py exhibit a weaker affinity for this substrate. Calorimetic and 1H NMR measurements showed that the host–guest adducts are mainly stabilized by charge–charge interactions and hydrogen bonds involving the ammonium function of PMG and the nonprotonated nitrogen atom of the pyridine linker.

Co(II) complexes with tripodal N-donor ligands: Thermodynamics of formation in anaerobic conditions and oxygen binding

The complex formation of Co(II) with N-donor ligands in dimethylsulfoxide (DMSO) is investigated by means of calorimetric and spectroscopic methods. The ligands considered in this work are tripodal polyamines and polypyridines: 2,2′,2′′-triaminotriethylamine (TREN), tris(2-(methylamino)ethyl)amine (Me3TREN), tris(2-(dimethylamino)ethyl)amine (Me6TREN), tris[(2-pyridyl)methyl]amine (TPA) and 6,6′-bis-[bis-(2-pyridylmethyl)aminomethyl]-2,2′-bipyridine (BTPA).These ligands are characterized by a systematic modification of the donor groups in order to study how their structure is related to the stability of the complexes formed and to their ability to bind oxygen. A comparison with thermodynamic data for similar Cd(II) systems as well as with data referred to linear tetra-amines in DMSO is also made. The solvent effect on the nature and stability of the species formed is discussed. DFT calculations are carried out to explain the trend in thermodynamic parameters for Me6TREN. Only Co(TREN)2+ is able to bind oxygen and two successive species (μ-superoxo and μ-peroxo) are formed. The kinetics of oxygen uptake by Co(TREN)2+ is found to be less solvent-dependent than other Co(II)–polyamine complexes when the formation of the mononuclear μ-superoxo complex is considered.

Prediction of microscopic protonation constants of polybasic molecules via computational methods: A complete microequilibrium analysis of spermine

For the first time, a simple methodology is reported for theoretical calculation of microscopic protonation constants of polybasic molecules in solution. Density functional theory study was used for complete microequilibrium analysis of spermine, H2N(CH2)3NH(CH2)4NH(CH2)3NH2, a linear tetraamine with 16 known microspecies. A general thermodynamic cycle is proposed to calculate protonation microconstants of polybasic molecules using calculated micro-ΔG values in aqueous solution. The microscopic protonation constants were determined with considering both the most abundant and most stable conformers for all microspecies. The results show that the microscopic protonation constants derived from the most abundant conformers (i.e., linear conformers in which the intramolecular hydrogen bonding does not exist) are in good agreement with the corresponding available experimental data. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2011

ChemInform Abstract: Crystal Structures and Reactivity of 3a,5a,8a,10a-Tetraazaperhydropyrene Derivatives. An Alternative Approach to Selective Nitrogen Alkylation of 1,4,8-11-Tetraazacyclotetradecane (Cyclam).

1-Alkyl and 1,8-dialkyl-1,4,8,11-tetraazacyclotetradecanes (alkyl = benzyl or methyl) were synthesised through cis -aminal of cyclam which was obtained by reaction of glyoxal and cyclam. The corresponding trans -aminal was synthesised from the respective linear tetraamine and glyoxal followed by cyclisation using 1,2-dibromoethane. The trans -aminal derivatives cannot be used for preparation of cyclam or its derivatives due to exceptional stability of the aminal bridge. The different reactivity of both cis - and trans -aminals is discussed on the basis of the X-ray structures determined for a series of the cyclam derivatives and could be explained by steric hindrance in the trans -aminals.

Complete gas-phase proton microaffinity analysis of five linear tetraamines containing two ethylenediamine residues

Density functional theory (DFT) and ab initio (Hartree–Fock) calculations employing the 6-31G∗∗ basis set were used to determine gas-phase proton microaffinities ( PA n,i ) of five linear tetraamines with general formula NH 2(CH 2) 2NH(CH 2) n NH(CH 2) 2NH 2 (where n = 2, 3, 4, 5 and 6). The corresponding proton macroaffinities ( PA ¯ n ) were calculated according to our recently established method with and without considering Boltzmann distribution of microspecies. The results showed that there are good correlations between the calculated proton macroaffinities, PA ¯ n , and proton overallaffinities, log PA ¯ ov , of these tetraamines in the gas phase with corresponding protonation macroconstants, log K n , and overall protonation constants, log β 4 , in solution, respectively.

A tertiary-branched tetra-amine, N4-aminopropylspermidine is a major cellular polyamine in an anaerobic thermophile, Caldisericum exile belonging to a new bacterial phylum, Caldiserica

Acid-extractable cellular polyamines of thermophilic Caldisericum exile belonging to a new bacterial phylum, Caldiserica were analyzed by HPLC and GC. The coexistence of an unusual tertiary brancehed tetra-amine, N4-aminopropylspermidine with spermine, a linear tetra-amine, as the major polyamines in addition to putrescine and spermidine, is first reported in the moderate thermophile isolated from a terrestrial hot spring in Japan. Linear and branched penta-amines were not detected. The novel cellular polyamine profile found in the moderate thermophile has never been observed within various bacteria and archaea previously analyzed.

Polynuclear Complexes: Two Amino−Phenol Macrocycles Spaced by Several Linear Polyamines; Synthesis, Binding Properties, and Crystal Structure

The synthesis and characterization of the new polytopic ligands 1,14-bis(3,6,9-triaza-15-hydroxybicyclo[9.3.1]pentadeca-11,13,1(15)-trien-6-yl)-3,6,9,12-tetraazatetradecane L1, 1,15-bis(3,6,9-triaza-15-hydroxybicyclo[9.3.1]pentadeca-11,13,1(15)-trien-6-yl)-3,6,10,13-tetraazapentadecane L2, and 1,16-bis(3,6,9-triaza-15-hydroxybicyclo[9.3.1]pentadeca-11,13,1(15)-trien-6-yl)-3,7,10,14-tetraazahexadecane L3, containing two equal amino-phenol macrocycles spaced by several linear tetraamines, are reported. The basicity and coordination behavior toward the Cu(II) ion were potentiometrically determined in aqueous solution at 298.1 K. All the ligands show similar acid-base properties behaving as octaprotic bases in the examined pH range (pH = 2-12). The acid protons of L1-L3 cannot be removed under the experimental conditions used; thus, the main deprotonated species obtainable in aqueous solution are the neutral ligands, having amphionic character as demonstrated by UV-vis experiments. These species are able to form mono-, di-, and trinuclear Cu(II) complexes having stoichiometry [CuL](2+), [Cu(2)L](4+), and [Cu(3)L](6+), respectively, that can lose one or two protons giving rise to [CuH(-1)L](+), [Cu(2)H(-2)L](2+), and [Cu(3)H(-2)L](4+). Depending on the used ligand to metal molar ratio, the mono-, di-, or trinuclear species prevail over the others in solution. Both di- and trinuclear complexes are able to add secondary ligands (such as OH(-)), and in some cases two Cu(II) can cooperate to stabilize them by coordinating the guest in a bridged conformation. The structure of the [Cu(2)L3](4+) cation was resolved by X-ray analysis of the {[Cu(2)L3](ClO(4))(4) x 3 H(2)O}(2) x H(2)O crystalline complex. It shows that each Cu(II) is penta-coordinated by one phenolate oxygen, two amine functions, belonging to one macrocyclic unit, and two amine functions of the spacer; in this species the distance between the two Cu(II) is about 5.3 A.

ATP and triphosphate anions complexation by bis-linear tetraamines: Strong interactions at neutral pH

The host–guest binding interaction involving two bis-linear tetraamines, namely 1,3-xylenylbis-1,4,8,11-tetraazaundecane ( L 1 ) and 2,6-dimethylpyridinylbis-1,4,8,11-tetraazaundecane ( L 2 ), with triphosphate and ATP anions is reported. These polyamines, obtained by linking two linear tetraamines with an aromatic spacer, are able to form in aqueous solution and around neutral p[H], very stable complexes with the targeted anionic substrates by means of electrostatic interactions such as hydrogen bonds. This study, investigated by potentiometric and NMR measurements in solution, clearly highlights the different coordination schemes exhibited by these anions according to their inorganic or organic nature; particularly, concerning ATP, the role of the aromatic linker in the complexation, through π-stacking interactions with the adenine part, is evidenced.

Synthesis of a New Linear-Cyclic Ditopic Polyazaligand with a Xylenyl Linker

The synthesis of a new linear-cyclic ditopic polyazaligand with a xylenyl linker 1 is described. The sequence is based on the stoichiometric reaction of a dissymmetrical biselectrophilic reagent, p-(chloromethyl)benzyl-p-toluenesulfonate, with phosphorylcyclam to give rise to an original intermediate possessing a p-chloroxylenyl pendant arm. The subsequent reaction of this compound with glyoxal-protected linear tetraamine, followed by deprotection steps, leads to the desired ditopic ligand with a good overall yield.

Synthesis and Characterisation of Some Hexadentate Schiff-base Ligands Containing the Piperazine Moiety

Ten hexadentate (N4O2, N4S2 and N6) Schiff-base ligands have been prepared by condensation of various aldehydes and two different linear tetraamines containing the piperazine moiety. The products have been characterised by melting point, elemental analysis and various spectroscopic methods such as: FT-IR, 1H, 13C NMR, and EI mass spectrometry. The complex [Co{N, N'-bis[(pyridin-2-ylmethylene)ethyl]piperazine}][ClO4]2 has been prepared.

Synthesis of a New Ditopic Ligand Possessing Linear and Cyclic Tetraaza Subunits

An easy‐to‐run route to a new ditopic ligand possessing linear and cyclic tetraaza subunits is described. In the first step, the reaction consists in the preparation of a triprotected cyclam bearing a 3‐bromopropyl pendant side chain. A subsequent reaction with a bisaminal protected linear tetraamine gives, after deprotection, the desired ditopic ligand.

Cyclohexanedione Bisaminals as Intermediates for Cyclen, Homocyclen, and Cyclam Synthesis.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Cyclohexanedione Bisaminals as Intermediates for Cyclen, Homocyclen, and Cyclam Synthesis

A new easy‐to‐run route to cyclen, homocyclen, and cyclam is proposed, based on the cyclization with dibromo‐ or ditosyloxy‐derivatives of bisaminal intermediates obtained by condensation of the appropriate linear tetraamine with cyclohexanedione. In the cyclization step, the use of cesium carbonate instead of potassium carbonate as proton trapper caused a remarkable increase of yields.

Synthesis of three dissymmetrical pentaamines via bisaminals of linear tetraamines

Bisaminals of linear tetraamines were selectively N-monofunctionalised with acrylonitrile in a Michael-type addition giving rise, after reduction, to three open-chain dissymmetrical pentaamines, bearing a new aminopropyl group on one terminal nitrogen atom.

Reaction of polyamines with diethyloxalate: a convenient route for the synthesis of tetraazacycloalkanes

The reactivity of various polyamines with diethyloxalate has been investigated. It appears that, in similar experimental conditions, primary diamines give predominantly (2+2) adducts while the use of secondary benzylated polyamines results in (1+1) condensation. Although the intermediate tetraamides formed in the first case are extremely poorly soluble and show very slow reactivity towards reducing agents, cyclam has been obtained by using ultrasounds during the reaction of the corresponding tetraoxomacrocycle with BH3/THF. The (1+1) cyclization reaction of diversely N-benzylated linear tetraamines, whose selective syntheses have been devised herein, gives access to various N-benzylated cyclens and cyclams. New macrocyclic ligands containing both amine and amide type nitrogen atoms have been formed as intermediates in these syntheses. Two compounds containing an aminal function exhibit an unexpected reactivity, leading to the formation of new bisaminal products whose structures have been established by X-ray diffraction.

Molecular Basis of Inward Rectification: Structural Features of the Blocker Defined by Extended Polyamine Analogs

Polyamines cause inward rectification of Kir K(+) channels by blocking deep within the channel pore. We investigated structural constraints of polyamine block of strongly rectifying mutant K(ATP) channels (Kir6.2[L164C,N160D,C166S] + SUR1). We studied three groups of polyamine analogs: 1) conformationally restricted linear tetra-amines with a cycloalkyl or alkene group between the second and third amines (CGC-11047, CGC-11093, CGC-11099, and CGC-11098), 2) conformationally restricted linear deca-amines with a cycloalkyl or alkene group between the fifth and sixth amines (CGC-11150, CGC-11179, and CGC-11241), and 3) cyclic tetra-amines (CGC-11174, CGC-11197, CGC-11199, and CGC-11254). All linear analogs cause a voltage-dependent block similar to that of spermine, but slightly weaker (at 1 microM, V(1/2) for spermine block = -10 +/- 1 mV, Z = 2.9 +/- 0.1, n = 19; V(1/2) for analogs varies from polyamine -7 to +10 mV, Z = 2.6-3.9). These data indicate tolerance for conformational restriction and an upper limit to the voltage dependence of the blocking process. There was no voltage-dependent block by the cyclic compounds; instead, they induce irreversible rundown of the current. Structural models of Kir channels suggest that a narrow entry at the top of the cytoplasmic pore may exclude cyclic analogs from the inner cavity, thereby explaining the structure-activity relationship that we observe.

Powerful N‐Monoalkylation of Linear Tetraamines via Bisaminal Intermediates

AbstractThe bisaminals obtained through the condensation of two linear tetraamines with glyoxal or pyruvic aldehyde were selectively alkylated with bromo‐ or α,ψ‐dibromoalkanes in good yields at one of the secondary amino functions to give rise to N‐monoalkylated tetraamines or linear octaamines. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

Bis‐Aminals of Linear Tetraamines: Kinetic and Thermodynamic Aspects of the Condensation Reaction

AbstractThe kinetic and thermodynamic aspects of the condensation reaction of dicarbonyl compounds with linear tetraamines were examined in the light of identification of intermediates and DFT calculations. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)