Maleate Ion Research Articles

Determination of Salt Forms of New Psychoactive Substances by Ion Chromatography

Objective To establish an ion chromatography method for the salt form determination of new psychoactive substances （NPS）. Methods The method of conducting qualitative and quantitative analysis of six types of organic acid ions （acetate ion, tartrate ion, maleate ion, oxalate ion, fumarate ion, citrate ion） and five types of inorganic anions （fluoride ion, chloride ion, nitrate ion, sulfate ion, phosphate ion） in NPS sample by ion chromatography was developed. The salt forms of 222 seized NPS samples （103 samples with synthetic cannabinoids, 81 samples with cathinones, 44 samples with phenylethylamines, 12 samples with tryptamines, 7 samples with phencyclidines, 6 samples with piperazines, 2 samples with aminoindenes, 26 samples with fentanyls and 43 samples with other types of NPS） were analyzed by this method. Results Each anion had good linearity in the corresponding linear range, the correlation coefficients （r） were greater than 0.999, the limits of detection were 0.01-0.05 mg/L, and the limits of quantitative were 0.1-0.5 mg/L. Except that 5F-BEPIRAPIM was hydrochloride, the salt forms of the other 102 synthetic cannabinoids were all base. The salt form of 81 cathinone samples, 44 phenylethylamine samples, 7 phencyclidine samples and 2 aminoindene samples were all hydrochloride. The salt forms of tryptamine samples included base, hydrochloride, fumarate and oxalate. The salt forms of piperazine samples included base and hydrochloride. The salt forms of fentanyl samples and samples of other types included base, hydrochloride and citrate. Conclusion Ion chromatography is a simple, accurate and efficient method for determining the salt form of NPS samples, which makes the qualitative and quantitative conclusions of NPS more scientific and rigorous.

Features of the Thermolysis of Li, Na, and Cd Maleates

Processes of the multi-stage decomposition of maleic acid and Li, Na, and Cd maleates in an inert atmosphere are studied via thermal analysis with synchronous analysis of the composition of the released gases. Reaction mechanisms are proposed according to the data on the mass loss stages determined via thermal analysis, gaseous products, and the final solid decomposition products. It is shown that when heated to 700°C, Li and Na carbonates incorporated into the porous carbon matrix are the final products. Above 350°C, cadmium is reduced from oxide to metal and evaporates to form a porous carbon residue as the only product of thermolysis. All carbon products are X-ray amorphous. Maleic acid decomposes completely into gaseous products in the range of 133–239°C. The maleate ion is more stable in the structure of lithium maleate than in free maleic acid, and Na and Cd cations reduce its stability.

Design and synthesis of malonohydrazide based colorimetric receptors for discrimination of maleate over fumarate and detection of F-, AcO- and AsO2- ions.

In this study, we have designed and synthesized two new organic receptors R1 and R2 based on malonohydrazide for the recognition of biologically important anions. The receptor R1 capable of colorimetric discrimination of maleate over fumarate ion, exhibit significant color change from pale yellow to wine red due to intermolecular hydrogen bond between the R1 and maleate ion, supported by 1HNMR titration, where the peak at δ12.0ppm attributed to the NH proton experiences a downfield shift upon binding with maleate ion. Receptor R1, equipped with two electron-withdrawing NO2 moieties as the chromogenic signaling unit enhance the hydrogen bonding tendency and acidity, and thus when comparing with receptor R2, R1 displayed substantial higher redshift (∆λmax) of 148nm, 143nm, and 140nm towards F-, AcO-, and maleate anion in the DMSO. In addition, the synthesized receptors R1 and R2 are able to detect F-, AcO-, and AsO2- ions as their sodium salts in an aqueous solution with visual color change. Receptor R1 exhibit electrochemical response towards F- and AcO- ions. The receptors R1 and R2 are successfully applied for quantitative detection of F- ion in the toothpaste solution in an aqueous medium. Additionally, R1 and R2 exhibit fluorescence enhancement towards F- and AcO- ions in the DMSO. As well, R1 and R2 demonstrate to be potentially useful colorimetric chemosensor for sensing maleate ion using the test strip. The theoretical calculation based on TD-DFT corroborates well with the experimental results of the receptors R1 and R2 with fluoride, acetate and maleate.

Crystal Structure of Diisopropylammonium Hydrogen Maleate

Use of salts and co-crystals of active pharmaceutical ingredients (APIs) as a method for tuning their delivery and activity is an area of growing interest. Modifying API properties such as solubility by finding new salts that employ similar hydrogen-bonding have been successful. In an effort to further study the hydrogen-bonding patterns of the maleate ion with other diisopropylammonium we report here the synthesis and diisopropylammonium maleate. The salt was isolated from reaction between diisopropylamine and maleic acid in methanol. The results of elementary analyzes (CHN) showed the presence of the nitrogen atom of diisopropylamine, carbon atoms and hydrogen. The IR spectrum of diisopropylammonium hydrogen maleate, showed the presence of two intense bands due to the vibrations of symmetricand anti-symmetric valence of the carboxylate group and a wide absorption due to the NH₂ groups of the cation. Those which has been confirmed by crystallography. The asymmetric unit contains one diisopropylammonium cation, iPr₂NH₂⁺ and one hydrogen maleate anion. In the structure, anions which present an inner O-H…O hydrogen bond are linked to cations through N-H…O hydrogen bonds leading to infinite chains. Chains are connected to their neighbours through weak C-H…O hydrogen bonds affording a layer. The study of the interactions of diisopropylammonium hydrogen menaleate, by the presence of hydrogen bonds leading to supramolecular architectures has shown the possibility of its use in Active Pharmaceutical Ingrédients (API).

Особенности термолиза малеатов Cu и La

Salts of carboxylic acids are widely used in organic synthesis, in the preparation of catalysts and nanocomposites of metals in the carbon matrix by thermolysis of maleates, acrylates or acetylenedicarboxylates of these metals; however, the studies of the thermal destruction process of such compounds are fragmentary. The processes of multi-stage decomposition of Cu and La maleates in an inert atmosphere were studied by the method of simultaneous thermal analysis with the analysis of the composition of evolved gases. Reaction mechanisms have been suggested that correspond to the gaseous products and the final solid decomposition product determined during the thermal steps of mass loss. The formation of nano-dispersed copper oxides and lanthanum oxocarbonate included in the porous carbon matrix has been shown. The results of thermal analysis have allowed us to identify common features of the maleate thermolysis. First, the decomposition of maleate ion or maleic acid is always accompanied by the formation, along with water and carbon dioxide, of two products containing a double or triple C–C bond: acrylic acid and acetylene in approximately equal amounts. Second, the presence of multiple bonds in the molecules of the initial substances and in the molecules of the gaseous products of thermolysis leads to their polymerization and further to formation of the carbon residue. The amount of this residue is the highest in the case of decomposition of lanthanum maleate and the lowest in the case of copper maleate. Third, the thermolysis of metal maleate results in a matrix consisting of a carbon polymer with particles of metals (Cu) or metal oxides / carbonates in the form of nanodispersed crystals evenly distributed in this matrix. With the use of electron microscopy the morphology and particle size of the products of the thermolysis of La and Cu maleates were determined. The thermolysis products are composites of spherical La 2 O 2 (CO 3 ) particles (2–5 µm in diameter) and Cu 2 O, CuO, Cu (10–500 nm in diameter), evenly distributed in the carbon matrix. The analysis of the thermolysis mechanism on the basis of the data on the magnitude of mass loss at each stage, thermal effects, as well as on the composition of gaseous products and on the phase composition of the final solid products of thermolysis allowed us to suggest a consistent initial formula of La and Cu maleates.

Dihydrocyclam dimaleate [H2(cyclam)(maleate)2

The asymmetric unit of the title mol­ecular salt [systematic name: 1,4,8,11-tetraazacyclotetradecane-1,8-diium bis(3-carboxy­prop-2-enoate)], C10H26N4 2+·2C4H3O4 −, contains two half-cations (both completed by crystallographic inversion symmetry) and two maleate anions. The cyclam macrocycles adopt trans-III conformations, supported by two intra­molecular N—H⋯O hydrogen bonds. The O-bonded H atom of each maleate ion is disordered over two positions with an occupancy ratio of 0.61 (5):0.39 (5): each one generates an intra­molecular O—H⋯O hydrogen bond. In the crystal, the cations are linked to the anions by N—H⋯O hydrogen bonds, generating [001] chains.

Olanzapinium Salts, Isostructural Solvates, and Their Physicochemical Properties

Solubility and dissolution play a crucial role in the activity and efficacy of an oral drug. Olanzapine is an antipsychotic drug of the Biopharmaceutics Classification System (BCS) class II category. Several solvates, cocrystals, salts, and amorphous forms of olanzapine have been prepared to study materials properties and its X-ray crystal structures were classified. We report herein a few salts, solvates, and solvate polymorphs of olanzapine to improve the physicochemical properties and study novel structural motifs. Olanzapinium dimaleate monofumaric acid is the first case of a ternary cocrystal of an active pharmaceutical ingredients (API) in the CSD database with maleate ion and fumaric acid coformers. The olanzapine disalts, olanzapinium dipicrate, dimaleate, and dimaleate monofumaric acid, contain a novel structural motif, different from the dimer motif characteristic of the four structural categories reported in the literature.

Thermolysis of copper(II) salts of maleic acid. Synthesis of metal-polymer composites

The thermal decomposition of neutral ([Cu(H2O)(C4H2O4)]) and acidic ([Cu(H2O)4](C4H3O4)2) maleates can conventionally be divided into four stages: (1) dehydration, (2) polymerization, (3) isomerization of the maleate ion to the trans form with the simultaneous reduction Cu(II) → Cu(I), and (4) decarboxylation of copper(I) fumarate. The third and fourth stages of the decomposition of these salts coincide. The residue after the thermolysis of copper(II) maleates in a He flow is a composite consisting of aggregates from 50 nm to several microns in size. Spherical conglomerates (50–200 nm) containing many spherical Cu particles (5–10 nm) are incorporated into the organic polymer matrix of these aggregates.

On the Intramolecular Hydrogen Bond in Solution: Car-Parrinello and Path Integral Molecular Dynamics Perspective.

The issue of the symmetry of short, low-barrier hydrogen bonds in solution is addressed here with advanced ab initio simulations of a hydrogen maleate anion in different environments, starting with the isolated anion, going through two crystal structures (sodium and potassium salts), then to an aqueous solution, and finally in the presence of counterions. By Car-Parrinello and path integral molecular dynamics simulations, it is demonstrated that the position of the proton in the intramolecular hydrogen bond of an aqueous hydrogen maleate anion is entirely related to the solvation pattern around the oxygen atoms of the intramolecular hydrogen bond. In particular, this anion has an asymmetric hydrogen bond, with the proton always located on the oxygen atom that is less solvated, owing to the instantaneous solvation environment. Simulations of water solutions of hydrogen maleate ion with two different counterions, K(+) and Na(+), surprisingly show that the intramolecular hydrogen-bond potential in the case of the Na(+) salt is always asymmetric, regardless of the hydrogen bonds to water, whereas for the K(+) salt, the potential for H motion depends on the location of the K(+). It is proposed that repulsion by the larger and more hydrated K(+) is weaker than that by Na(+) and competitive with solvation by water.

Investigation of hydrogen bond effects on the hyperpolarizability of 2-Aminopyridinium maleate (2APM) complex and determining the non-linear optical susceptibility of the molecular crystal of 2APM

2-Aminopyridinium maleate (2APM) is a recently discovered organic acid-base complex that crystallizes in a non-centrosymmetric space group Pc and hence has a nonzero second-order optical susceptibility. In 2APM the cation (aminopyridinium ion) is connected to the anion (maleate ion) through hydrogen bonds (N1-H10–O2 and N2-H12–O1), we have calculated the molecular properties of 2APM for varying strength of these hydrogen bonds. It is observed that the molecular hyperpolarizabilty varies for varying strength of these hydrogen bonds. These observations are interpreted in terms of the change in nature of the hydrogen bond interaction as its strength is varied. Macropscopic second-order optical susceptibility (d 0) of 2APM is obtained using the calculated value of molecular hyperpolarizability and the reported crystal structure of 2APM. In order to study the influence of molecular packing on the macroscopic non-linear optical property of the crystal, susceptibility calculations are repeated for 2-methyl-4nitroaniline (MNA) crystal, which is a very well known non-linear optical organic crystal with an exceptionally high value of second-order optical susceptibility. A comparison between the non-linear optical property of 2APM and MNA crystals is given. Comparing the values of d 0 of 2APM crystals with that of urea shows that the nonlinear optical response of 2APM crystals will be nearly 10 times that of a urea crystal.

ZandEisomers of butenedioic acid with 2-amino-1,3-thiazole: 2-amino-1,3-thiazolium hydrogen maleate and 2-amino-1,3-thiazolium hydrogen fumarate

Maleic acid and fumaric acid, the Z and E isomers of butenedioic acid, form 1:1 adducts with 2-amino-1,3-thiazole, namely 2-amino-1,3-thiazolium hydrogen maleate (2ATHM), C(3)H(5)N(2)S(+) x C(4)H(3)O(4)(-), and 2-amino-1,3-thiazolium hydrogen fumarate (2ATHF), C(3)H(5)N(2)S(+) x C(4)H(3)O(4)(-), respectively. In both compounds, protonation of the ring N atom of the 2-amino-1,3-thiazole and deprotonation of one of the carboxyl groups are observed. The asymmetric unit of 2ATHF contains three independent ion pairs. The hydrogen maleate ion of 2ATHM shows a short intramolecular O-H...O hydrogen bond with an O...O distance of 2.4663 (19) A. An extensive hydrogen-bonded network is observed in both compounds, involving N-H...O and O-H...O hydrogen bonds. 2ATHM forms two-dimensional sheets parallel to the ab plane, extending as independent parallel sheets along the c axis, whereas 2ATHF forms two-dimensional zigzag layers parallel to the bc plane, extending as independent parallel layers along the a axis.

DFT Study of Proton Dynamics in the Potassium Hydrogen Maleate Crystal: the Infrared Versus the Inelastic Neutron Scattering Spectra

Abstract The structure, harmonic frequencies and infrared (IR) intensities of the fundamental transitions in potassium hydrogen maleate (KHM) crystal have been computed using the BLYP/6-31G** method with periodic boundary conditions. The inelastic neutron scattering (INS) intensities of the fundamental transitions were evaluated and compared with the experimental INS spectra of hydrogenated sample and isotopic analogues of the KHM crystal; the agreement is reasonable good. Spectroscopic manifestations of the proton dynamics in the strong intramolecular H-bond were clarified by comparison of the computed frequencies of the IR and INS-active fundamental transitions. Due to several reasons, the number of the bands and their relative intensity were found to differ between the INS and IR spectra of the KHM crystal. Reduced masses for the asymmetric O…H…O stretching vibrations of the hydrogen maleate ion appear to be larger 1 a.m.u. because of the strong coupling between the bridging proton motion and the various intramolecular vibrations.

Anharmonic interactions and infrared bandshape of the hydrogen bond vibration of potassium hydrogen (deuterium) maleate crystals

The spectral profiles of the hydrogen bond vibrations in the potassium hydrogen maleate (KHM) crystal and its deuterated analogue (KDM) were studied theoretically taking into account the Fermi resonance (FR) effect and strong coupling between the hydrogen bond vibration and lattice phonons. In addition, ab initio calculations of the frequencies and intensities of the H(D)-maleate ion for both C 2v and C s symmetry were made. It was found that C s symmetry has to be used and that practically all intense bands have a contribution from the OH vibration. It was shown that, taking into account all the factors: ab initio results, FR and anharmonicity of vibrations, the experimental spectra for both KHM and KDM crystals can be explained adequately. Anharmonic constants were obtained as a result of fitting theoretical spectra to the experimental ones.

Anionic clays as hosts for anchored synthesis: Interlayer bromination of maleate and fumarate ions in nickel–zinc layered hydroxy double salt

Anionic clay-like nickel zinc hydroxyacetate, Ni 3Zn 2(OH) 8(OAc) 2·2H 2O was ion exchanged with maleate and fumarate ions. While the maleate enters as monoanion, fumarate enters as dianion. Also these anions take up different orientations in the interlayer region. The intercalated organic species could be reacted with bromine water in such a way that the brominated product remains intercalated making the reaction a true intracrystalline reaction. The stereochemistry of the reaction of the intercalated fumarate was identical to that of the free fumarate ion – both yielding only the anti addition product. While free maleate ion yielded only the anti addition product, the intercalated maleate ion yielded a small percentage of the syn addition product along with the anti addition product. The organic products could be quantitatively recovered by anion exchange with oxalate ions.

Synthesis and magneto-structural correlation of a new maleato bridged copper(II) coordination polymer

A one-dimensional (1-D) copper(II) coordination polymer [Cu(maleate)(2,2′-bipyridyl)]n·2H2O has been synthesised. Single crystal X-ray diffraction study reveals that maleate ion bridges two adjacent copper(II) centres along the chain in a syn–anti fashion. A complete cryomagnetic investigation of the title complex correlates well with the distorted square pyramidal geometry of the central copper(II) ion and bridging nature of the maleate. A τ value of 0.26 indicates the distortion towards tbp coordination allowing the \({\rm d}_{x^2 - y^2 }\) magnetic orbital to acquire some\({\rm d}_{z^2 }\) character leading to a weak antiferromagnetic interaction having J = −0.26 cm−1. The complex has also been firmly established from several other instrumental techniques like Fourier transform infrared (FT-IR) and EPR spectroscopies.

Benzoylmethyltriphenylphosphonium hydrogen maleate: supramolecular layer formation due to C—H...O interactions

The molecule of the title salt, C26H22OP+.C4H3O4−, consists of a benzoyl­methyl­tri­phenyl­phospho­nium cation (HBPPY) and a hydrogen maleate anion. Owing to a strong O—H⋯O intraionic hydrogen bond, each hydrogen maleate ion forms a ring, described by the graph-set notation S11(7). Several C—H⋯O interactions are present between the cations and anions and contribute to the stabilization of the crystal structure.

Bis(2-aminopyridinium) maleate.

Two cyclic eight-membered hydrogen-bonded rings exist in the title compound, 2C(5)H(7)N(2)(+) x C(4)H(2)O(4)(2-), involving the 2-aminopyridinium and maleate ions. The dihedral angle between the two pyridinium rings hydrogen bonded to the maleate ion is 74.80 (4) degrees. The maleate anion lies on a twofold axis and is linked to the pyridinium cations by intermolecular N-H.O hydrogen bonds. The heterocycle is fully protonated, which enables amino-imino tautomerization.

Aminopyrimidine-carboxyl(ate) interactions in trimethoprim maleate, an antifolate drug.

In the title cocrystal, trimethoprim maleate [2,4-diamino-5-(3,4,5-trimethoxybenzyl)pyrimidin-1-ium maleate], C(14)H(19)N(4)O(3)(+).C(4)H(3)O(4)(-), the trimethoprim molecule is protonated at N1. The carboxyl group of the maleate ion makes a specific double hydrogen bond of type N-H.O with the 2-amino group and the protonated N1 atom of the trimethoprim cation which is similar to the carboxylate-trimethoprim cation interaction observed in the complex of dihydrofolate reductase with trimethoprim. The pyrimidine moieties of trimethoprim cations are centrosymmetrically paired through a pair of N-H.N hydrogen bonds involving the 4-amino group and the pyridinium N3 atom of a symmetry-related molecule. One of the O atoms at the maleate carboxylate group bridges the 2-amino and 4-amino groups on either side of the paired trimethoprim cations. The other O atom of the carboxylate group forms an intramolecular O-H.O hydrogen bond with the carboxyl group. These characteristic hydrogen bonds result in infinite two-dimensional aggregation of rings into a supramolecular ladder, which is further crosslinked through weak C-H.O interactions with methoxy groups of neighbouring trimethoprim molecules to form a layered structure.

Structure and dynamics of the symmetric hydrogen bond in potassium hydrogen maleate: a neutron scattering study

The crystal structure of potassium hydrogen maleate KH(OOC–CHCH–COO) has been studied at 300, 14 and 5 K using three-dimensional single-crystal neutron diffraction data. There is no evidence for any phase transition. The crystal structure is orthorhombic, P bcm (D 2h ll), with four entities in the unit cell ( Z=4), in accord with previous X-ray diffraction work. The ion is nearly planar and deviation from C 2v symmetry is negligible. The short internal hydrogen bond parallel to the c axis, R O⋯O=2.427(1) Å at 5 K, is symmetrical with the proton located at the center. Inelastic neutron scattering (INS) spectra, from 16 to 4000 cm −1, of the fully hydrogenated sample and partially deuterated analogues, KH(OOC–CDCD–COO) and KD(OOC–CHCH–COO), have been recorded for powdered samples and aligned single crystals at 20 K. Complex spectral profiles are observed for the stretching mode of the hydrogen bond, ν a OHO, and for the totally symmetric out-of-plane deformation of the maleate ion. An isotopic mixture of KH(OOC–CDCD–COO), 20%, and KD(OOC–CDCD–COO), 80%, reveals that intermolecular coupling is negligible. Frequencies and intensities are amenable to symmetrical potential functions with a central minimum between secondary minima at higher energy. The INS and infrared band profiles suggest that the planar conformation with C 2v symmetry of the maleate ring is unstable in excited vibrational states. The quantum nature of the hydrogen bond is emphasised with the concept of `hydrogen bonding/anti-bonding' states.

Methylamine and Dimethylamine Salts of the Hydrogen Maleate Ion

Methylammonium hydrogen maleate, CH6N+.C4H3O4−, crystallizes in space group Pnam with two independent anions in the asymmetric unit having crystallographic mirror planes bisecting the C=C bonds. Dimethylammonium hydrogen maleate, C2H8N+.C4H3O4−, crystallizes in space group P21/n without crystallographic symmetry constraints on the hydrogen maleate ion and this anion possesses also almost perfect mirror-plane symmetry. One of the anions in the methylammonium salt displays significant deviation from planarity [−12.00 (9)°]. The symmetry of the three anions and the difference in their conformations are rationalized from the hydrogen-bond interactions in the two salts.