Novel naphthalimide–indomethacin hybrids as potential antitumor agents: effects of linkers on hypoxic/oxic cytotoxicity and apoptosis-inducing activity

Abstract  

A series of novel naphthalimide–indomethacin hybrids with different linkers were designed and synthesized. Their antitumor activity was evaluated against HeLa, A549, P388, HL-60, MCF-7, HCT-8, and A375 cancer cell lines in vitro. Preliminary results showed that the hybrids had moderate cytotoxic activity with 50% inhibition concentration (IC ₅₀) values of ~10⁻⁵ M, and could effectively induce apoptosis in HeLa cells. More importantly, the amide derivatives had better cytotoxic and proapoptotic activity than their ester counterparts, whereas the ester derivatives had hypoxic preferred cytotoxicity and might be used as promising candidates of prodrug in hypoxic tumor cells. This work provides a novel class of naphthalimide–indomethacin hybrids with unique antitumor activity for further optimization.     

Synthesis and anticancer activity of some 1,5-diaryl-3-(3,4,5-trihydroxyphenyl)-1H-pyrazolo[4,3-e][1,2,4]triazines

Abstract  

The deregulation of cell cycle components in cancer cells has provided a rationale for the development of small molecule inhibitors of cyclin-dependent kinases as novel anticancer drugs. A series of 1,5-diaryl-3-(3,4,5-trihydroxyphenyl)-1H-pyrazolo[4,3-e][1,2,4]triazines was synthesized and their kinase inhibitory activity and cytotoxicity against several cancer cell lines has been evaluated. Some of the compounds of the series exhibited induction of caspase-dependent cell death and inhibition of cyclin-dependent kinase 2 (CDK2).     

Spectrophotometric determination of uranium with arsenazo-III in the presence of N-cetyl-N,N,N-tri-methylammonium bromide as surfactant

A simple, sensitive and efficient spectrophotometric method is proposed for rapid determination of uranium using arsenazo-III in perchloric acid. The reaction between arsenazo-III and U(VI) was instantaneous in 3 mol L⁻¹ HClO_4. N-cetyl-N,N,N-trimethylammonium bromide was used for increasing the sensitivity and selectivity of the complex. The absorbance remains stable for over 48 h in the presence of surfactant. The method allows the determination of uranium in the range of 1–20 μg g⁻¹ with a molar absorptivity of 3.9 × 10⁵ dm³ mol⁻¹ cm⁻¹ at 681 nm. Sandell’s sensitivity of the complex was calculated to be 6.4 ng cm⁻² at λ_max 681 nm. A significant enhancement was achieved in the sensitivity of the proposed method whereas, Relative Standard Deviation was reduced from 4.5 to 1.7% in the presence of surfactant. Among various diverse ions studied, fluoride, cyanide, citrate, sulfate and phosphate interfere beyond the tolerance limit. Among cations only Cr³⁺ and Co²⁺ decreased the normal absorbance. The validity of the reported method was tested by determining uranium in the environmental water samples and Standard Reference Material. The results agreed closely with the reported values. The proposed method is new, easy in operation and better in sensitivity than many of the existing methods.     

Novel acenaphthopyrazine derivatives as antitumor agents against MCF-7 cells: molecular synthesis, optical properties, and DNA-binding studies

Abstract  

A series of novel acenaphthopyrazine derivatives was synthesized from acenaphthylene-1,2-dione via three steps, including bromination, cyclization, and S_NAr^H reaction. These new compounds exhibited potential antiproliferative activity against MCF-7 cells in vitro, and 3-[2-(dimethylamino)ethylamino]acenaphtho[1,2-b]pyrazine-8,9-dicarbonitrile exhibited the highest activity (IC ₅₀ = 4.60 μM). DNA-binding experiments suggested that these derivatives bind to DNA through intercalation with intrinsic binding constants K all above 10⁵ M⁻¹. Optical property studies indicated that these compounds have long emission wavelength (λ _em > 560 nm), high quantum yields in toluene (Φ_f = 0.59 for 3-(morpholin-4-yl)acenaphtho[1,2-b]pyrazine-8,9-dicarbonitrile), and large Stokes shift (ΔS > 130 nm).     

Investigation on the thermal decomposition some heterodinuclear NiII-MII complexes prepared from ONNO type reduced Schiff base compounds ( M II=ZnII, CdII)

N,N′-bis(salicylidene)-1,3-propanediamine (LH₂), N,N′-bis(salicylidene)-2,2′-dimethyl-1,3-propanediamine (LDMH₂), N,N′-bis(salicylidene)-2-hydroxy-1,3-propanediamine (LOH₃), N,N′-bis(2-hydroxyacetophenylidene)-1,3-propanediamine (LACH₂) and N,N′-bis(2-hydroxyacetophenone)-2,2′-dimethyl-1,3-propanediamine (LACDMH₂) were synthesized and reduced to their phenol-amine form in alcoholic media using NaBH₄ (L^HH₂, LDM^HH₂, LOH^HH₂, LAC^HH₂ and LACDM^HH₂). Heterodinuclear complexes were synthesized using Ni(II), Zn(II) and Cd(II) salts, according to the template method in DMF media. The complex structures were analyzed using elemental analysis, IR spectroscopy, and thermogravimetry. Suitable crystals of only one complex were obtained and its structure determined using X-ray diffraction, NiLAC^H·CdBr₂·DMF₂, space group orthorhombic, Pbca, a=20.249, b=14.881, c=20.565 ? and Z=8. The heterodinuclear complexes were seen to be of [Ni·ligand·MX₂·DMF₂] structure (ligand=L^H2−, LDM^H2−, LOH^H2−, LAC^H2−, LACDM^H2−, M=Zn^II, Cd^II, X=Br⁻, I⁻). Thermogravimetric analysis showed irreversible bond breakage of the coordinatively bonded DMF molecules followed by decomposition at this temperature.     

Design and synthesis of 3-acyl-2(3H)-benzoxazolone and 3-acyl-2(3H)-benzothiazolone derivatives

Abstract  

A simpler and efficient “green” method using solid sodium hydroxide in a solvent mixture of acetone/water was found to catalyze N-acylation of 2(3H)-benzoxazolones and 2(3H)-benzothiazolones for facile and rapid synthesis of N-acyl derivatives in excellent yields. This method was applied to the synthesis of a series of 132 compounds employing a variety of acyl chlorides.     

Synthesis, structure, and properties of a binuclear Fe(III) complex with N-(1-propanol)-N,N-bis(3-tert-butyl-5-methyl-2-hydroxybenxyl)amine

Mannich reaction of 2-Amino propanol, 2-tert-butyl-4-methylphenol, and formaldehyde in the ratio of 1:2:2 provides a new compound, N-(1-propanol)-N,N-bis(3-tert-butyl-5-methyl-2-hydroxybenxyl)amine (H₃L), which has been characterized by X-ray crystallography and elemental analysis. In the presence of Et₃N, the reaction of H₃L and FeCl₃·6H₂O gives a dinuclear Fe(III) complex [Fe₂L₂] 1, which has been characterized by X-ray crystallography, magnetic measurement, and cyclic voltammetry. The value of μ_eff at room temperature (5.97 μ_B) is much less than the expected spin-only value (8.37 μ_B) of two high spin (hs) Fe³⁺ (S = 5/2) ions [μ = g[∑ZS(S + 1)]^1/2], indicating there are strong coupling interactions between Fe³⁺ ions. The magnetic behavior of 1 denotes the occurrence of intramolecular antiferromagnetic interactions (J = −13.35 cm⁻¹ ). CV of 1 reveals two reversible waves at 0.433 and 1.227 V versus AgCl/Ag, which can be ascribed to the successive redox coupling of Fe^IIFe^II/Fe^IIIFe^II and Fe^IIIFe^II/Fe^IIIFe^III, respectively.     

Synthesis,cytotoxicity and apoptosis-inducing activity of novel 1H-benzo[d]imidazole derivatives of dehydroabietic acid

With the expectation of finding new and effective antitumor drugs, a series of novel N-(1H-benzo[d]imidazole-2-yl)-benzamide/benzenesulfonamide derivatives of dehydroabietic acid were synthesized and evaluated for cytotoxic activity against three human cancer cell lines (MCF-7, HeLa, and HepG2 cells) and one human normal hepatocyte cell line (LO2). As a result, a number of derivatives showed moderate to good antitumor activities. Among them, compound 8h exhibited the most potent activities against three cancer cell lines with IC₅₀ values of 0.87 ± 0.18, 9.39 ± 0.72, and 8.31 ± 0.64 μM, respectively, and was less active to normal hepatocyte LO2 cells. Further mechanism studies revealed that compound 8h could arrest the cell cycle of MCF-7 cells at S phase and induce the apoptosis of MCF-7 cells in ROS-mediated mitochondrial pathway.     

Synthesis,spectroscopic, thermal and biological aspect of mixed ligand copper(II) complexes

Derivative of 8-hydroxyquinoline i.e. Clioquinol is well known for its antibiotic properties, drug design and coordinating ability towards metal ion such as Copper(II). The structure of mixed ligand complexes has been investigated using spectral, elemental and thermal analysis. In vitro anti microbial activity against four bacterial species were performed i.e. Escherichia coli, Pseudomonas aeruginosa, Serratia marcescens, Bacillus substilis and found that synthesized complexes (15–37 mm) were found to be significant potent compared to standard drugs (clioquinol i.e. 10–26 mm), parental ligands and metal salts employed for complexation. The kinetic parameters such as order of reaction (n = 0.96–1.49), and the energy of activation (E _a = 3.065–142.9 kJ mol⁻¹), have been calculated using Freeman–Carroll method. The range found for the pre-exponential factor (A), the activation entropy (S* = −91.03 to−102.6 JK⁻¹ mol⁻¹), the activation enthalpy (H* = 0.380–135.15 kJ mol⁻¹), and the free energy (G* = 33.52–222.4 kJ mol⁻¹) of activation reveals that the complexes are more stable. Order of stability of complexes were found to be [Cu(A⁴)(CQ)OH] · 4H₂O > [Cu(A³)(CQ)OH] · 5H₂O > [Cu(A¹)(CQ)OH] · H₂O > [Cu(A²)(CQ)OH] · 3H₂O     

Antimycobacterial 3-phenyl-4-thioxo-2H-1,3-benzoxazine-2(3H)-ones and 3-phenyl-2H-1,3-benzoxazine-2,4(3H)-dithiones substituted on phenyl and benzoxazine moiety in position 6

A series of forty-five derivatives of 3-phenyl-4-thioxo-2H-1,3-benzoxazine-2(3H)-ones and forty-five derivatives of 3-phenyl-2H-1,3-benzoxazine-2,4(3H)-dithiones was synthesised. The compounds exhibited in-vitro activity against Mycobacterium tuberculosis, M. kansasii (two strains), and M. avium. The most active derivatives were more active than isonicotinhydrazide (INH). The quantitative relationships between the structure and antimycobacterial activity were calculated. The activity against M. tuberculosis increased with the lipophilicity of the substituents.     

Accumulation of Exopolysaccharides in Liquid Suspension Culture of Nostoc flagelliforme Cells

The liquid suspension culture of dissociated Nostoc flagelliforme cells was investigated. It was found that the growth rate of N. flagelliforme cells and the accumulation of exopolysaccharides (EPS) increased prominently when NaNO₃ and KH₂PO₄ were added in the liquid BG-11culture medium though phosphate had little effect on EPS yield for specific mass of cells. N. flagelliforme cells grew well at 25 °C and neutral pH, however, a lower or higher temperature and weak alkaline can promote EPS accumulation. With the increase of the light intensity, the growth rate of N. flagelliforme cells and the EPS accumulation increase accordingly. When N. flagelliforme cells was cultured in BG-11 medium added with 2.5 g L⁻¹ of NaNO₃ and 0.956 g L⁻¹ of KH₂PO₄ at 25 °C with 60 μmol photon m⁻² s⁻¹ of light intensity, 1.05 g L⁻¹ cell density and 89.9 mg L⁻¹ EPS yield were achieved respectively. Adopting the optimal conditions established in flask culture, the liquid culture of N. flagelliforme cells in 20-L photobioreactor for 16 days was conducted and a maximum biomass of 1.32 g L⁻¹ was achieved, which was about 17.6-fold of that in the initial inoculation. The yield of EPS was 228.56 mg L⁻¹and about 2.23-fold of that in flask culture. Moreover, the polysaccharides’ material was released into the culture medium during cell growth. These released polysaccharides (RPSs), which can be easily recovered from the medium, are favorable for industrial applications.     

A new octahedral cobalt(III) complex of (1,8)- bis (2-hydroxybenzamido)-3,6-diazaoctane incorporating phenolate-amide-amine coordination: synthesis, X-ray crystal structure, ligand substitution and redox activity with sulfur(IV) and l -ascorbic acid

The octahedral complex, [Co^III(HL)]·9H₂O (H₄L = (1,8)-bis(2-hydroxybenzamido)-3,6-diazaoctane) incorporating bis carboxamido-N-, bis sec-NH, phenolate, and phenol coordination has been synthesized and characterized by analytical, NMR (¹H, ¹³C), e.s.i.-Mass, UV–vis, i.r., and Raman spectroscopy. The formation of the complex has also been confirmed by its single crystal X-ray structure. The cyclic voltammetry of the sample in DMF ([TEAP] = 0.1 mol dm⁻³, TEAP = tetraethylammonium perchlorate) displayed irreversible redox processes, [Co^III(HL)] → [Co^IV(HL)]⁺ and [Co^III(HL)] → [Co^II(HL)]⁻ at 0.41 and −1.09 V (versus SCE), respectively. A slow and H⁺ mediated isomerisation was observed for the protonated complex, [Co^III(H₂L)]⁺ (pK = 3.5, 25 °C, I = 0.5 mol dm⁻³). H₂Asc was an efficient reductant for the complex and the reaction involved outer sphere mechanism; the propensity of different species for intra molecular reduction followed the sequence: [{[Co^III(HL)],(H₂Asc)}–H]⁻ <<< {[Co^III(H₂L)],(H₂Asc)}⁺ < {[Co^III(HL)],(H₂Asc)}. A low value (ca. 3.7 × 10⁻¹⁰ dm³ mol⁻¹ s⁻¹, 25 °C, I = 0.5 mol dm⁻³) for the self exchange rate constant of the couple [Co^III(HL)]/[Co^II(HL)]⁻ indicated that the ligand HL³⁻ with amido (N-) donor offers substantial stability to the Co^III state. HSO₃⁻ and [Co^III(HL)] formed an outer sphere complex {[Co^III(HL)],(HSO₃⁻)}, which was slowly transformed to an inner sphere S-bonded sulfito complex, [Co^III(H₂L)(HSO₃)] and the latter was inert to reduction by external sulfite but underwent intramolecular S^IV → Co^III electron transfer very slowly. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Solubility and Ionic Processes in the Cu X 2? MX ?H2O ( X ?=Cl?, Br?; M +=Li+, Na+, K+, NH4+, Cs+) Systems

 Solubility isotherms in the CuBr₂−MBr−H₂O (M ⁺ = Li⁺, Na⁺, Cs⁺) systems at 298.15 K were measured. The results together with other available literature data for copper chloride and bromide systems were treated by hydration analysis, and comparative discussion of ionic processes taking place in the respective saturated solutions was performed.     

Synthesis and Antimicrobial Evaluation of Some Chalcones and Their Derived Pyrazoles, Pyrazolines, Isoxazolines, and 5,6-Dihydropyrimidine-2-(1 H )-thiones

Chalcones were synthesized by a base catalyzed Claisen-Schmidt condensation reaction. Bromination of chalcones afforded the dibromo derivatives. Monobromo derivatives could be obtained by treating the corresponding dibromochalcones with dry benzene in the presence of triethylamine. Pyrazole derivatives were obtained by refluxing of dibromochalcones with phenylhydrazine or 2,4-dinitrophenylhydrazine in dry pyridine. Chalcones were treated with hydrazine hydrate or phenyl hydrazine in ethanol to afford Δ ²-pyrazolines and N-phenyl-Δ ²-pyrazolines. Condensation of chalcones with hydroxylamine hydrochloride or thiourea in ethanolic sodium hydroxide solution gave 4,5-dihydroisoxazoles and 5,6-dihydropyrimidine-2-(1H)-thiones. The prepared compounds were tested for antimicrobial activity against four different bacterial species displaying different degrees of antibacterial activities or inhibitory actions.     

Five-membered 2,3-dioxo heterocycles: LXXVI. Reaction of methyl 1-aryl-3-benzoyl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates with 6-amino-1,3-dimethylpyrimidine-2,4(1H,3H)-dione

Methyl 1-aryl-3-benzoyl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates reacted with 6-amino-1,3-dimethylpyrimidine-2,4(1H,3H)-dione to give methyl 11-aryl-12-benzoyl-9-hydroxy-4,6-dimethyl-3,5,10-trioxo-4,6,8,11-tetraazatricyclo[7.2.1.0^2,7]dodec-2(7)-ene-1-carboxylates which underwent thermal recyclization to 1-aryl-3-benzoyl-4-hydroxy-1′,3′-dimethylspiro[pyrrole-2,5′-pyrrolo[2,3-d]pyrimidine]-2′,4′,5,6′(1H,1′H,3′H,7′H)-tetraones.     

Mass spectra of new heterocycles: VIII. Fragmentation of 6-alkoxy- and 6-aryl(hetaryl)-3H-azepines under electron impact

The electron impact mass spectra of previously unknown 2-alkyl-6-alkoxy-, 2,3-trimethylene-6-alkoxy- and 2-alkyl-6-aryl(hetaryl)-3H-azepines were studied. All compounds give rise to stable molecular ions (I _rel = 44–100%) whose fragmentation pattern is determined mainly by the substituent on C⁶. Decomposition of the molecular ions derived from 6-alkoxy derivatives (R¹ = MeO, EtO, i-PrO) follows general relations typical of alkyl ethers. The main characteristic peaks in the mass spectra of 2-methyl-6-aryl- and 2-methyl-6-hetaryl-3H-azepines (R¹ = Ph, 1H-pyrrol-1-yl, 5-methylthiophen-2-yl) belong to even-electron rearrangement ions [M − H]⁺ and [M − Me]⁺, which have conjugated bi- and tricyclic structures, and products of their subsequent decomposition. Substituents in positions 2 (R²) and 3 (R⁴) [R⁴ = H, R² = Me, Et; R²R⁴ = (CH₂)₃] bring some specificity to the fragmentation pattern, but their contribution is not crucial. Original Russian Text ? L.V. Klyba, N.A. Nedolya, O.A. Tarasova, E.R. Zhanchipova, O.G. Volostnykh, 2009, published in Zhurnal Organicheskoi Khimii, 2009, Vol. 45, No. 4, pp. 610–621. For communication VII, see [1].     

New ionic liquid for inorganic cations analysis by capillary electrophoresis: 2-hydroxy- N , N , N -trimethyl-1-phenylethanaminium bis(trifluoromethylsulfonyl)imide (phenylcholine NTf2)

The potentialities of new ionic liquids (ILs) based on choline were evaluated as an electrophoretic medium in capillary electrophoresis for the analysis of alkaline and alkaline earth cations (Li⁺, K⁺, Na⁺, Cs⁺, Mg²⁺, Ba²⁺, Ca²⁺, and Sr²⁺) with indirect UV detection. Two types of capillaries were tested: an untreated fused silica and fused silica coated with a film of polyvinylalcohol. The coated capillary proved to be the best adapted for the metal ions studied. Moreover, it appeared that the nature of the ionic liquid anion influenced the baseline stability, and the bis(trifluoromethylsulfonyl) imide (NTf₂ ⁻) anion seemed to be the most efficient. These preliminary studies led us to synthesize a new ionic liquid, 2-hydroxy-N,N,N-trimethyl-1-phenylethanaminium NTf₂ (phenylcholine NTf₂). This liquid was able to act as the running electrolyte and probe, generating the background signal in indirect UV light and consequently simplifying the electrophoretic medium. Excellent baseline stability, good reproducibility, as well as good sensitivity of detection were obtained with this new ionic liquid. Thus, 510,000 plates/meter for Li⁺ with 40 mM IL were successfully obtained. The optimal concentration of IL was 20 mM with a detection limit ranging from 28 μg L⁻¹ for Li⁺ to 1,000 μg L⁻¹ for Cs⁺. This method (phenylcholine NTf₂ with polyvinylalcohol capillary) was applied to analyze different commercial source and mineral waters. Finally, the potentiality of this ionic liquid in nonaqueous capillary electrophoresis was explored. The use of phenylcholine NTf₂ with a fused silica capillary, in pure methanol medium and in the presence of acetic acid, made it possible to obtain separation selectivity different from that obtained in aqueous medium.     

2-(5-Benzoacridine)ethyl-p-toluenesulfonate as sensitive reagent for the determination of bile acids by HPLC with fluorescence detection and online atmospheric chemical ionization-mass spectrometric identification

2-(5-Benzoacridine)ethyl-p-toluenesulfonate (BAETS), a dual-sensitive probe, was reacted with bile acids in the presence of K₂CO₃ catalyst in dimethyl sulfoxide (DMSO) solvent to give BAETS–bile acid derivatives. Derivatives exhibited intense fluorescence (FL) with an excitation maximum at λ _ex 270 nm and an emission maximum at λ _em 510 nm. MS analysis using APCI-MS indicated that derivatives had excellent APCI-MS ionizability with percentage ionization δ values changing from 0 to 88.83% in aqueous acetonitrile and from 0 to 89.15% in aqueous methanol. The collision induced dissociation spectra of m/z [M + H]⁺ contained specific fragment ions at m/z [M + H−H₂O]⁺, [M + H−2H₂O]⁺, [M + H−3H₂O]⁺, 347.3, and 290.1. Repeatability was good for LC separation of BAETS–bile acid derivatives with aqueous acetonitrile as mobile phase. The relative standard deviations (RSDs) of retention time and peak area at 6.6 nmol mL⁻¹ levels with fluorescence detection (FL) were from 0.045 to 0.072% and from 2.16 to 2.73%, respectively. Excellent linear responses were observed, with regression coefficients >0.9995. The FL detection limits (S/N = 3) were in the range of 18.0–36.1 fmol. The online APCI-MS detection limits are in the range of 500–790 fmol (at a signal-to-noise ratio of 3).     

Solubility and Ionic Processes in the Cu X 2? MX ?H2O ( X ?=Cl?, Br?; M +=Li+, Na+, K+, NH4+, Cs+) Systems

Summary.  Solubility isotherms in the CuBr₂−MBr−H₂O (M ⁺ = Li⁺, Na⁺, Cs⁺) systems at 298.15 K were measured. The results together with other available literature data for copper chloride and bromide systems were treated by hydration analysis, and comparative discussion of ionic processes taking place in the respective saturated solutions was performed. Corresponding author. E-mail: jitka@prfdec.natur.cuni.cz Received August 6, 2002; accepted (revised) November 29, 2002 Published online April 3, 2003     

Thermodynamics of sodium 5-methylisophthalic acid monohydrate and sodium isophthalic acid hemihydrate

Two crystal samples, sodium 5-methylisophthalic acid monohydrate (C₉H₆O₄Na₂·H₂O, s) and sodium isophthalic acid hemihydrate (C₈H₄O₄Na₂·1/2H₂O, s), were prepared from water solution. Low-temperature heat capacities of the solid samples for sodium 5-methylisophthalic acid monohydrate (C₉H₆O₄Na₂·H₂O, s) and sodium isophthalic acid hemihydrate (C₈H₄O₄Na₂·1/2H₂O, s) were measured by a precision automated adiabatic calorimeter over the temperature range from 78 to 379 K. The experimental values of the molar heat capacities in the measured temperature region were fitted to a polynomial equation on molar heat capacities (C _p,m) with the reduced temperatures (X), [X = f(T)], by a least-squares method. Thermodynamic functions of the compounds (C₉H₆O₄Na₂·H₂O, s) and (C₈H₄O₄Na₂·1/2H₂O, s) were calculated based on the fitted polynomial equation. The constant-volume energies of combustion of the compounds at T = 298.15 K were measured by a precise rotating-bomb combustion calorimeter to be Δ_c U(C₉H₆O₄Na₂·H₂O, s) = −15428.49 ± 4.86 J g⁻¹ and Δ_c U(C₈H₄O₄Na₂·1/2H₂O, s) = −13484.25 ± 5.56 J g⁻¹. The standard molar enthalpies of formation of the compounds were calculated to be Δ _f H _m ^θ (C₉H₆O₄Na₂·H₂O, s) = −1458.740 ± 1.668 kJ mol⁻¹ and Δ _f H _m ^θ (C₈H₄O₄Na₂·1/2H₂O, s) = −2078.392 ± 1.605 kJ mol⁻¹ in accordance with Hess’ law. The standard molar enthalpies of solution of the compounds, Δ _sol H _m ^θ (C₉H₆O₄Na₂·H₂O, s) and Δ _sol H _m ^θ (C₈H₄O₄Na₂·1/2H₂O, s), have been determined as being −11.917 ± 0.055 and −29.078 ± 0.069 kJ mol⁻¹ by an RD496-2000 type microcalorimeter. In addition, the standard molar enthalpies of hydrated anion of the compounds were determined as being Δ _f H _m ^θ (C₉H₆O₄ ²⁻, aq) = −704.227 ± 1.674 kJ mol⁻¹ and Δ _f H _m ^θ (C₈H₄O₄Na₂ ²⁻, aq) = −1483.955 ± 1.612 kJ mol⁻¹, from the standard molar enthalpies of solution and other auxiliary thermodynamic data through a thermochemical cycle.