N-methylpiperazine Research Articles

Volumetric and Viscous Properties at Several Temperatures for Binary Mixtures of N-Methylpiperazine with Methylcyclohexane or n-Heptane

The data of density and viscosity for binary mixtures of N-methylpiperazine (NMP) with methylcyclohexane (MCH) or n-heptane have been measured from T = 298.15 K to T = 313.15 K at atmospheric pressure. Excess volume, VmE, for the binary mixtures are then calculated. Positive values of VmE are observed over the entire composition range, and the maximum value is 0.622 cm3·mol−1 at 313.15 K. The excess results are discussed in terms of the changes of molecular interactions in the mixtures, and the data of VmE are fitted against the composition with the Redlich−Kister type equation. The viscosities have also been correlated with several semiempirical equations. These physical property data and calculations provide valuable information on the development and application of piperazine derivatives.

Detection ofnitric oxide in tissue samples by ESI-MS

A novel method to determine nitric oxide (NO) in biological tissue samples with minimal interference from the cellular detritus is described. Methylpiperazinobenzenediamine, consisting of an o-phenylenediamine and a methyl piperazine group, was chosen as a probe for the detection of NO by mass spectrometry (MS) in biological tissue samples. The o-phenylenediamine group reacts with NO to form a characteristic benzotriazole. The product was identified using electrospray ionization mass spectrometry (ESI-MS) and the method validated within the range of 95-1900 nM. NO levels associated with tissue biopsies (approximately 10 mg) from rat vasculature and intestine tissue biopsies have been successfully determined. The different rates of NO generated from tissue samples under hypoxic and normoxic conditions have been studied by this simple and sensitive method.

Synthesis and biological evaluation of nitrogen-containing chalcones as possible anti-inflammatory and antioxidant agents

A novel series of nitrogen-containing chalcones were synthesized by Mannich reaction and were screened for anti-inflammatory related activities such as inhibition of cyclooxygenase-2 (COX-2), trypsin and β-glucuronidase. The antioxidant potential was demonstrated using 1,1-diphenyl-2-picryl hydrazine (DPPH) radical scavenging activity. The results of the above studies shows that the compounds synthesized were found to be effective inhibitors of above pro-inflammatory enzymes, and were found to be possess moderate radical scavenging potential. Overall, the results of the studies reveal that the chalcones with N-methyl piperazine methyl and piperidine methyl substitution ( 4c, 3b, 4d, 6b) seems to be important for inhibition of β-glucuronidase. Whereas the chalcones with piperidine methyl substitution ( 8b, 7b, 7c, 6c, 4b, 3c, 3b) were observed as effective inhibitors of COX-2, while the same compounds were found to be less reactive against COX-1 as compared to COX-2.

Discovery of substituted N′-(2-oxoindolin-3-ylidene)benzohydrazides as new apoptosis inducers using a cell- and caspase-based HTS assay

We report the discovery of a series of substituted N′-(2-oxoindolin-3-ylidene)benzohydrazides as inducers of apoptosis using our proprietary cell- and caspase-based ASAP HTS assay. Through SAR studies, N′-(4-bromo-5-methyl-2-oxoindolin-3-ylidene)-3,4,5-trimethoxybenzohydrazide ( 3g) was identified as a potent apoptosis inducer with an EC 50 value of 0.24 μM in human colorectal carcinoma HCT116 cells, more than a 40-fold increase in potency from the initial screening hit N′-(5-bromo-2-oxoindolin-3-ylidene)-3,4,5-trimethoxybenzohydrazide (2a). Compound 3g also was found to be highly active in a growth inhibition assay with a GI 50 value of 0.056 μM in HCT116 cells. A group of potentially more aqueous soluble analogs were prepared and found to be highly active. Among them, compound 4e incorporating a methyl piperazine moiety was found to have EC 50 values of 0.17, 0.088 and 0.14 μM in human colorectal carcinoma cells HCT116, hepatocellular carcinoma cancer SNU398 cells and human colon cancer RKO cells, respectively. Compounds 3g and 4e were found to function as inhibitors of tubulin polymerization.

New piperazine‐based polymerizable monoquaternary cationic surfactants: Synthesis, polymerization, and swelling characteristics of gels

AbstractMonoquaternary cationic polymerizable surfactants of type N‐acryloyl‐N′‐methyl‐N′‐alkyl piperazinium bromide based on piperazine heterocycle was synthesized by reacting N‐acryloyl‐N′methyl piperazine with the corresponding n‐alkyl bromide (decyl, dodecyl, tetradecyl, and hexadecyl) in anhydrous acetone at room temperature. The resulting surfactants were deliquescent to display any sharp melting points. The surface activity was studied by surface tension measurements. Due to the complex head group geometry of these surfactants, the critical micelle concentration value was high in comparison to the analogous alkyltrimethyl ammonium bromides of similar alkyl chain length. The surfactants were polymerized by micellar (in water) and isotropic (in benzene) conditions and the resulting polymers were characterized by solubility and viscosity studies. The polymers prepared in water showed higher viscosity than the ones prepared in benzene as a result of micellar aggregation in water. The reduced viscosity of the polymers in polar solvents such as methanol and dimethyl formamide (DMF) showed polyelectrolyte‐like behavior, whereas nonelectrolyte behavior was observed in chloroform. pH‐responsive hydrogels were prepared by polymerizing the surfactants in the bicontinuous phase of a microemulsion. The resulting polymers did not exhibit any definite micro/nanostructure due to cross‐polymerization of the hydrophilic oil in the bicontinuous network structure. The gels were highly responsive to changes in pH of the medium and showed high‐swelling degree in acidic media owing to the protonation of the tertiary nitrogen of the piperazine ring. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 2059–2072, 2009

Polycationic phosphorus dendrimers: synthesis, characterization, study of cytotoxicity, complexation of DNA, and transfection experiments

Four series of phosphorus dendrimers (generations 1 and 4) having various types of amine terminal groups (pyrrolidine, morpholine, methyl piperazine, or phenyl piperazine) are synthesized. After protonation, the fourth generations of three of them are found water-soluble, and used for several biological experiments. First, the cytotoxicity of these polycationic dendrimers towards three cell strains (one healthy: HUVEC, and two cancerous: HEK 293 and HeLa) is assayed and found low. Second, their ability to interact with DNA is tested by electrophoresis: the dendrimer terminated by pyrrolidinium groups is found efficient to form dendriplexes. Finally, the polycationic dendrimers are used as transfection agents to deliver single- and double-stranded DNA into the three above-mentioned cell strains. Here also the dendrimer having pyrrolidinium groups is found the most efficient.

Synthesis of some new 1,2,4-triazoles, their Mannich and Schiff bases and evaluation of their antimicrobial activities

4-Phenyl-5-pyridin-4-yl-4 H-1,2,4-triazole-3-thiol ( 3) was obtained in basic media via the formation of 2-isonicotinoyl- N-phenylhydrazinecarbothioamide ( 2), and converted to some alkylated derivatives ( 4a, b) and Mannich base derivatives ( 5a– c). 2-[(4-Phenyl-5-pyridin-4-yl-4 H-1,2,4-triazol-3-yl)thio]acetohydrazide ( 7) that was obtained by using compound 3 as precursor in two steps was converted to thiosemicarbazide derivative ( 8), Schiff base derivatives ( 9) and 5-{[(4-phenyl-5-pyridin-4-yl-4 H-1,2,4-triazol-3-yl)thio]methyl}-1,3,4-oxadiazole-2-thiol ( 10). Moreover, 5-{[(4-phenyl-5-pyridin-4-yl-4 H-1,2,4-triazol-3-yl)thio]methyl}-3-{[(2-morpholin-4-ylethyl)amino]methyl}-1,3,4-oxadiazole-2(3 H)-thione ( 11) was synthesized via reaction of compound 10 with 2-(4-morpholino)ethylamine. The treatment of compound 8 with NaOH gave 4-(4-methylphenyl)-5-{[(4-phenyl-5-pyridine-4-yl-4 H-1,2,4-triazol-3-yl)thio]methyl}-4 H-1,2,4-triazole-3-thiol ( 12), while the acidic treatment of compound 8 afforded 5-{[(4-phenyl-5-pyridin-4-yl-4 H-1,2,4-triazol-3-yl)thio]methyl}-2(4-methylphenyl)-amino-1,3,4-thiadiazole ( 14). N-Methyl derivative of compound 14 and a Mannich base derivative of compound 12 were synthesized from the reactions of these precursors with methyl iodide and methyl piperazine, respectively. All newly synthesized compounds were screened for their antimicrobial activities. The antimicrobial activity study revealed that all the compounds screened showed good or moderate activity except compounds 3, 5c, 7, 9c, 9e, 9g, 9h, 11, and 13.

First stereoselective synthesis and assignment of the absolute configuration of the nebracetam eutomer and derivatives

(−)-Nebracetam 1 was stereoselectively prepared for the first time, allowing the determination of its absolute configuration as ( R). The pivotal intermediate in the synthesis, 1-benzyl-4-[( S)-2,2-dimethyl-1,3-dioxolan-4-yl]-pyrrolidin-2-one 6, was previously obtained in 60% yield and 90% ee from an enoate derived from d-mannitol. Two approaches were investigated to synthesize ( R)-(−)-nebracetam 1 and analogues 4 and 5 from 6. Compound 6 was transformed into WEB-1868 2. Mesylation of the hydroxyl group in 2, followed by nucleophilic substitution with azide and reduction led to target 1. Compounds 4 and 5 were synthesized by using morpholine and N-methyl piperazine as nucleophiles. Compounds 4 and 5 were also prepared, in higher yields and similar ee, through the reductive amination of aldehyde 10, obtained in two steps from 6.

Study of Microemulsion Polymerization Conditions on the Preparation of “Stimuli” Responsive Copolymer Nanogels of N‐Acryloyl‐N′‐Methyl Piperazine and Methyl Methacrylate

pH responsive copolymer nanogel particles of N‐acryloyl‐N′‐methyl piperazine (AcrNMP) and methyl methacrylate (MMA) were prepared by a suitable oil‐in‐water type microemulsion polymerization. Effect of microemulsion polymerization conditions such as water content, surfactant‐to‐monomer ratio, amount of monomer, and crosslinker content were studied. The nanogel particles showed spherical morphology with narrow size distribution. The nanogels swelled excessively in acidic solutions reaching a diameter of 750 nm and de‐swelled to 350 nm in basic solutions. This pH response to swelling is due to the protonation of N′‐methyl piperazine nitrogen that leads to electrostatic interactions within the nanogel.

Synthesis, spectral, magnetic, electrochemical and kinetic studies of copper(II), nickel(II) and zinc(II) acetate complexes derived from phenol based ‘end-off’ ligands: Effect of p-substituents

A new class of symmetric, end-off, N-methyl piperazine armed binucleating ligands 2,6-bis(4-methyl piperazin-1-yl-methyl)-4-acetyl phenol (HL 1) and 2,6-bis[(4-methyl piperazin-1-yl-methyl)]-(4-methylcarboxy) phenol (HL 2) were synthesized by the Mannich reaction. Their mononuclear and binuclear Cu(II), Ni(II) and Zn(II) complexes have been synthesized. These complexes were characterized by elemental analysis, infra-red and electronic spectral analysis. In the electronic spectra, the lower electron withdrawing nature of the C(O)CH 3 p-substituent (HL 1) compared with the C(O)OCH 3 p-substituent (HL 2) of the phenolic ring causes a red shift in the LMCT-charge transfer band. The mononuclear Cu(II) complexes 1 and 7 have a magnetic moment value close to the spin only value with four hyperfine EPR signals. The binuclear Cu(II) complexes 4 and 10 illustrate an antiferromagnetic interaction ( μ eff 1.56 and 1.55 BM) at 298 K with a broad EPR signal. A variable temperature magnetic moment study of the binuclear copper(II) complexes shows that the extent of antiferromagnetic coupling increases in the order: CHO [K. Shanmuga Bharathi, A. Kalilur Rahiman, K. Rajesh, S. Sreedaran, P.G. Aravindan, D. Velmurugan, V. Narayanan, Polyhedron 25 (2006) 2859] < C(O)CH 3 < C(O)OCH 3 (−2 J values 134 [Shanmuga Bharathi et al., mentioned above], 149 and 158 cm −1, respectively). The mononuclear Ni(II) complexes 2 and 8 are square planar and diamagnetic. The six coordinated binuclear Ni(II) complexes 5 and 11 show a magnetic moment value of 2.96 and 2.95 BM, respectively. Electrochemical studies of the complexes reveal that all the mononuclear complexes show a single irreversible one-electron transfer reduction wave and the binuclear complexes show two irreversible one-electron transfer reduction waves in the cathodic region. There is an anodic shift in the reduction of the metal centres when the electron withdrawing nature of the p-substituent of the phenolic ring increases. The catecholase activity of the mono and binuclear copper(II) complexes, using pyrocatechol as a model substrate, and the hydrolysis of 4-nitrophenyl phosphate using the mono and binuclear copper(II), nickel(II) and zinc(II) complexes as catalysts showed that the binuclear complexes have higher rate constant values than those of the corresponding mononuclear complexes. A comparison of the spectral, electrochemical and magnetic behaviour of the complexes derived from the ligands is discussed on the basis of the substituent at the para position of the phenolic ring.

Synthesis and reactivity of a C3-symmetric trinuclear zinc(ii) hydroxide catalyst efficient at phosphate diester transesterification

Inspired by trinuclear Zn(II) sites in enzymatic systems, a ligand system containing three preorganized (2-pyridyl)methyl piperazine moieties anchored onto a rigid C3-symmetric triphenoxymethane platform has been developed for preorganizing three zinc ions into an environment conducive to intramolecular interaction. Zinc(II) binding by this ligand has been analyzed by means of potentiometric measurements in 50% (v/v) CH3CN-H2O solutions. Subsequently a C3-symmetric trinuclear Zn(II) hydroxide complex of the C3-symmetric ligand was synthesized and fully characterized using NMR spectroscopy and X-ray crystallography. This complex induces a 16,900-fold rate enhancement in the catalytic cyclization of the RNA model substrate, 2-hydroxypropyl-p-nitrophenyl phosphate (HPNP, pH 6.7, 25 degrees C) over the uncatalyzed reaction with multiple catalyst turnovers. The observed differences in the pH-rate profile can be attributed to the varying concentration of various trinuclear zinc species. The trinuclear Zn(II) catalyst exhibits a higher hydrolytic activity compared to its mononuclear analogue. The reactivity and structural features of this trinuclear Zn(II) complex will be discussed.

Synthesis of new ‘end-off’ μ-phenoxo and bis-μ-acetato tri-bridged copper(II), nickel(II) and zinc(II) complexes: Spectral, magnetic, electrochemical and catalytic studies

A new end-off type acyclic ligand with two N-methyl piperazine arms, 2,6-bis[(4-methyl piperazin-1-yl)]-4-formyl phenol [L], has been synthesized by a simple Mannich reaction. The mono and binuclear complexes of Cu(II), Ni(II) and Zn(II) have been prepared. The complexes were characterized by elemental and spectral analysis. The EPR spectrum of the mononuclear copper complex shows four hyperfine splittings and the binuclear complex shows a broad signal due to an anti-ferromagnetic interaction. The room temperature magnetic moment of the mono and binuclear copper complexes are found to be 1.72 μ B ( μ eff) and 1.58 μ B ( μ eff), respectively. The mononuclear Ni(II) complex is square planar and diamagnetic, whereas the six-coordinated binuclear Ni(II) complex shows a magnetic moment value of 2.98 μ B ( μ eff). Cyclic voltammetric studies evidenced one irreversible reduction wave for all the mononuclear complexes and two irreversible one-electron reduction waves for the binuclear complexes are obtained in the cathodic region. In the anodic region, one irreversible oxidation wave for the mononuclear nickel(II) complex and two irreversible oxidation waves for the binuclear nickel(II) complexes are obtained. Kinetic studies on the oxidation of pyrocatechol to o-quinone using the mono and binuclear copper(II) complexes as catalysts and on the hydrolysis of 4-nitrophenylphosphate using the mono and binuclear copper(II), nickel(II) and zinc(II) complexes as catalysts were carried out. The binuclear complexes have higher rate constant values than those of the corresponding mononuclear complexes. The rate constant values for the complexes for the hydrolysis are in the order nickel(II) > copper(II) > zinc(II).

Synthesis and structure-directing effect of piperazinium hydroxides derived from piperazines for the formation of porous zeolites

A series of organic structure-directing agents (SDAs) derived from N-methyl piperazine are synthesized and first used in the zeolite synthesis. When the hydrothermal synthesis route is applied, SDA1, SDA3 and SDA4 are beneficial to the formation of ZSM-12 lattice, but SDA2 and SDA5 readily induce the nucleation and crystallization of ZSM-5 phase. When using the dry gel conversion route, only SDA5 yields a porous material similar to the ZSM-11 topology. Thus, synthesized zeolites have been confirmed by XRD and IR characterizations to possess characteristics of MFI, MEL and MTW lattices, respectively. The crystal size (1.0 × 9.3 μm) of ZSM-5 synthesized is measured to be much larger than those of ZSM-11 (0.10∼0.50 μm) and ZSM-12 (0.80∼2.0 μm). The TG curve of ZSM-12 shows a two-stage weight loss in the flow of air, while those of ZSM-5 and ZSM-11 contain three-stage weight losses in air. 13C CP MAS NMR spectra confirm the encapsulation of SDAs in the pore channels of as-synthesized ZSM-5, ZSM-11 and ZSM-12.

Viscosities and densities for binary mixtures of N-methylpiperazine with methanol, ethanol, n-propanol, iso-propanol, n-butanol and iso-butanol at 293.15, 298.15 and 303.15 K

Viscosity ( η) and density ( ρ) values are reported for binary mixtures of N-methylpiperazine (NMP) with methanol, ethanol, n-propanol, iso-propanol, n-butanol and iso-butanol over the entire range of mole fraction at 293.15, 298.15, and 303.15 K and atmospheric pressure. The viscosity deviation (Δ η), excess molar volume ( V E), and excess Gibbs energy of activation ( G *E) have been calculated. These results were fitted with Redlich–Kister type polynomial equation. All the investigated systems exhibit very large positive values of Δ η and G *E, and negative values of V E over the whole composition range. The obvious deviations attribute to the strong cross association between the alkanol and NMP molecules through the hydrogen bond of O H ⋯ N. The temperature has significant effect on Δ η and relatively slight effect on V E and G *E. From the experimental data, the thermodynamic functions of activation have been estimated for each binary mixture. The viscosity data have been correlated with several semi-empirical equations. Two-parameter equation of McAllister can give satisfactory results.

Effect of new synthesized piperazine derivative [1] containing 1, 2, 4 –triazole ring on the growth of some pathogenic microorganisms

This work describes the antimicrobial activity of newly synthesized 4-methyl (3-mercapto -4- phenyl -4H- 1,2,4-Triazole –5-yl) methyl piperazine. [1]. The newly synthesized piperazine derivative was obtained from basic cyclization of the intermediate product obtained from the reaction between acetic hydrizide –4-methyl piperazine and phenylisothiosyanate(1) .[1] The in vitro tests showed antimicrobial activity against two pathogenic bacteria viz; Staphylococcus aureus (gram positive) and Escherichia coli (gram negative), in addition to the dermatophyte pathogenic fungi Trichophyton rubrum. The screening antibacterial results illustrated below indicate that concentration [50mg/ml] showed the highest inhibitory effect against Escherichia coli, while the same concentration has a moderate activity againstStaphylococcus aureus.While the highest inhibitory effect against Trichophyton rubrum was achieved using the concentration [25 mg/ml].

Generic capillary electrophoresis conditions for chiral assay in early pharmaceutical development

Generic capillary electrophoresis (CE) conditions have been implemented for chiral separations in early pharmaceutical development. The chiral CE separations of several pharmaceutical samples at different stages of development, i.e., discovery, process chemistry, and investigative new drug application, have been obtained using sulfated beta-cyclodextrin (CD). Several sulfated beta-CDs have been screened to select an appropriate enantioselective agent. The use of a generic CE method allows for a convenient and rapid chiral recognition of different weak bases, with minimal or no method development. CE using sulfated beta-CD for the chiral separation of N-benzoyl methyl piperazine has been validated for linearity, precision, accuracy, limits of detection and quantitation (LOD, LOQ). Although less sensitive than a specific liquid chromatography method using a Chiralpak AD column, the overall performance of the chiral CE method was found comparable. Validation data demonstrate that a LOD of 0.1%, sufficient to fulfill regulatory requirements, is achievable by chiral CE.

A cGMP-dependent cascade enhances an l-type-like Ca 2+ current in identified snail neurons

We studied the impact of an NO-cGMP dependent signalling pathway on the high-voltage-activated (HVA) Ca 2+ current in identified neurons of the pulmonate snail, Helix pomatia, using Ba 2+ as charge carrier. The 3′,5′-cyclic guanosine monophosphate (cGMP) analogues, dibutyryl-cGMP and 8-bromo-cGMP, consistently induced a biphasic response, consisting of an increase superseded by a decline of the Ba 2+ current. The NO donor, sodium nitroprusside (SNP), modulated only in a minority of neurons the Ba 2+ current. Blockade of protein kinase activity with 1-[5-isoquinolinesulfonyl]-2 methyl piperazine (H 7), a nonselective protein kinase inhibitor, or Rp-8-pCPT-cGMP, a selective protein kinase G (PKG) inhibitor, decreased, whereas Rp-cAMP, a selective protein kinase A (PKA) inhibitor, increased the Ba 2+ current upon application of cGMP analogues or SNP. Okadaic acid or calyculin, inhibitors of protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A), augmented the Ba 2+ current. Under these conditions, cGMP analogues or SNP had an additive-enhancing effect on the Ba 2+ current. When neurons were exposed to the nonselective phosphodiesterase (PDE) inhibitor 3-isobutyl-1-methylxanthine (IBMX), cGMP analogues induced a persistent increase of the Ba 2+ current, whereas SNP induced a biphasic response. These data suggest coexistence of cGMP-PKG and cGMP-PDE pathways as well as crosstalk between cGMP and 3′,5′-cyclic adenosine monophosphate (cAMP) pathways, which converge on HVA Ca channels in Helix neurons. In this model, augmentation of the Ba 2+ current through HVA Ca channels is accomplished by PKA and PKG, whereas attenuation is mediated by PDEs, which prevent activation of protein kinases via hydrolysis of cyclic nucleotides.

Identification of 4-methylspinaceamine - a Pictet – Spengler condensation reaction product of histamine with acetaldehyde - in human urine

This study reports the first identification of 4-methylspinaceamine (4-MSPA)-a Pictet Spengler condensation reaction product of histamine with acetaldehyde-in human urine. 4-MSPA was identified and quantified as follows: the target compound was partially purified by solvent extraction from a urine sample spiked with N-methylpiperazine (N-MP) as an internal standard, then derivatized to a naphthylthiourea derivative with 1-naphthylisothiocyanate (NITC) and finally analyzed by HPLC. For verification, 4-MSPA was also analyzed by ion spray-mass spectrometry (IS-MS), using 4-MSPA- d 4 as an internal standard. The amount of 4-MSPA in human urine varied between individuals and from day-to-day, ranging from undetectable to 0.80 nmol/mL.

Synthesis and characterization of poly(N-acryloyl?-methyl piperazinium(+1)) tetrachlorometallate (II) compounds

The interactions of metal ions with poly(N-acryloyl N’-methyl piperazine) in the solid state were studied. The Cu(II) and Zn(II) compounds were prepared and characterized by means of elemental analysis; FT-IR, electronic spectroscopies, and thermogravimetric analysis. PM3 semiempirical calculations on the polymer conformations and the Zn(II) complex have been performed. The piperazine group in the polymer shows the conformations; namely; the chair and a distorted chair conformation. Both structures differ by just ca. 10 kcal/mol. In the compounds MCl4(PAPH)2 the MCl4 2- complex ion presents a distorted tetrahedral geometry. The electronic spectrum of the yellow Cu(II) coordination compound shows a band at 894 nm. In the IR spectra, an absorption band at 3020 cm-1 has been assigned to the v(N-H) stretching mode of the NH+ group. The protonated nitrogen atom is the one bonded to the methyl group due to the larger basicity according to the calculated electronic charge density and to the lower steric hindrance. The interaction of the MCl4 2- anion and the polymer is achieved by hydrogen bonding at the NH+ group and the chloride with N-H ···Cl distances lying betwen 1.7 to 3.3 A°.

ChemInform Abstract: Substituted 2‐(R)‐Methyl Piperazines as Muscarinic M2 Selective Ligands.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.