Structure Elucidation

Macrocyclic complexes of Cu ( II ), Ni ( II ), Co ( II ), and Zn ( II ) of a tetradentate Schiff base ligand derived from 3benzalideneacetoacetanilide and N -(2aminoethyl )-1,3propanediamine were synthesized . The nature of the complexes and the geometry have been inferred from their microanalytical data , magnetic susceptibility measurements , IR , UV -Vis , 1 H NMR , ESR , and mass spectral techniques . The low electrical conductance of the complexes supports the neutral nature . Monomeric nature of the complexes is assessed from their magnetic susceptibility values . The in vitro biological screening effects of the investigated compounds were tested against the bacteria E . coli , S . aureus , S . typhi , and K . pneumoniae by the well diffusion method using agar nutrient as the medium. A comparative study of minimum inhibitory concentration (MIC) values of the Schiff base and its complexes indicate that the metal complexes exhibit higher antibacterial activity than the free ligand and the control (streptomycin). The cyclic voltammetry method was used to probe the interaction of a Cu(II) complex with pUC18 DNA. Information of the binding ratio and intercalation mode can be obtained from its electrochemical data. Cyclic voltammetric measurements showed that the Cu(II) complex undergoes a reversible reduction at biologically accessible potentials. From the study, it is understood that the copper complex prefers to bind with DNA in Cu(II) rather than Cu(I) oxidation state. The DNA cleavage ability of the complexes was monitored by gel electrophoresis using supercoiled pUC18 DNA in tris-HCl buffer.

An application of the radiolysis method using X-ray synchrotron beam is developed as a novel approach to the synthesis of metal-organic films with controlled shapes and thickness. We demonstrate that a Langmuir monolayer deposited onto a silver ion-containing subphase, irradiated by an incident beam impinging below the critical angle for total reflection, induces the synthesis of a stable nanostructured silver-organic ultrathin film at the air-water interface. The X-ray scattering is also used to monitor in situ the structure of the silver layer during the synthesis process. The layer is observed by AFM after its transfer onto a silicon substrate. One observes a film thickness of 4.6 nm, in good agreement with the X-ray penetration depth, about 4.5 nm. The silver structure is oriented by the initial organic film phase. This experiment demonstrates the considerable potential of this approach to produce various controlled metal-organic films with a surfactant self-assembly as a template.

An application of the radiolysis method using X-ray synchrotron beam is developed as a novel approach to the synthesis of metal-organic films with controlled shapes and thickness. We demonstrate that a Langmuir monolayer deposited onto a silver ion-containing subphase, irradiated by an incident beam impinging below the critical angle for total reflection, induces the synthesis of a stable nanostructured silver-organic

An application of the radiolysis method using an X-ray synchrotron beam is developed as a novel approach to the synthesis of metal-organic films with controlled shapes and thickness. We demonstrate that a Langmuir monolayer deposited onto a silver ion containing subphase, irradiated by an incident beam impinging below the critical angle for total reflection, induces the synthesis of a stable nanostructured silver-organic ultrathin film at the air-water interface. The X-ray scattering is also used to monitor in situ the structure of the silver layer during the synthesis process. The layer is observed by atomic force microscopy after its transfer onto a silicon substrate. One observes a film thickness of 4.6 nm, in good agreement with the X-ray penetration depth, about 4.5 nm. The silver structure is oriented by the initial organic film phase. This experiment demonstrates the considerable potential of this approach to produce various controlled metal-organic films with a surfactant self-assembly as a template.

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A series of 1H-1,2,3-triazole analogs (7a-7d and 9a-9s) were synthesized via "click" chemistry and evaluated for in vitro carbonic anhydrase-II (bovine and human) inhibitory activity. The synthesis of intermediates, 7a and 7c, was achieved by using (S)-(-)ethyl lactate as a starting material. These compounds (7a and 7c) underwent Suzuki-Miyaura cross-coupling reaction with different arylboronic acids in 1,4-dioxane, reflux at 90-120 °C for 8 h using Pd(PPh 3 ) 4 as a catalyst (5 mol%), and K 2 CO 3 (3.0 equiv)/K 2 PO 4 (3.0 equiv) as a base to produce target 1H-1,2,3-triazole molecules (9a-9s) for a good yield of 67-86%. All the synthesized compounds were characterized through NMR spectroscopic techniques. Furthermore, all those compounds have shown significant inhibitory potential for both sources of carbonic anhydrase-II (CA-II). In the case of bCA-II, compounds 9i, 7d, 9h, 9o, 9g, and 9e showed potent activity with IC50 values in the range of 11.1-17.8 µM. Whereas for hCA-II, compounds 9i, 9c, 9o, and 9j showed great potential with IC50 values in the range of 10.9-18.5 µM. The preliminary structure-activity relationship indicates that the presence of the 1H-1,2,3-triazole moiety in those synthesized 1H-1,2,3triazole analogs (7a-7d and 9a-9s) significantly contributes to the overall activity. However, several substitutions on this scaffold affect the activity to several folds. The selectivity index showed that compounds 9c, 9k, and 9p are selective inhibitors of hCA-II. Kinetics studies showed that these compounds inhibited both enzymes (bCA-II and hCA-II) in a competitive manner. Molecular docking indicates that all the active compounds fit well in the active site of CA-II. This study has explored the role of 1H-1,2,3-triazole-containing compounds in the inhibition of CA-II to combat CA-II-related disorders.

A series of 1H-1,2,3-triazole analogs (7a-7d and 9a-9s) were synthesized via "click" chemistry and evaluated for in vitro carbonic anhydrase-II (bovine and human) inhibitory activity. The synthesis of intermediates, 7a and 7c, was achieved by using (S)-(-)ethyl lactate as a starting material. These compounds (7a and 7c) underwent Suzuki-Miyaura cross-coupling reaction with different arylboronic acids in 1,4-dioxane, reflux at 90-120 °C for 8 h using Pd(PPh 3 ) 4 as a catalyst (5 mol%), and K 2 CO 3 (3.0 equiv)/K 2 PO 4 (3.0 equiv) as a base to produce target 1H-1,2,3-triazole molecules (9a-9s) for a good yield of 67-86%. All the synthesized compounds were characterized through NMR spectroscopic techniques. Furthermore, all those compounds have shown significant inhibitory potential for both sources of carbonic anhydrase-II (CA-II). In the case of bCA-II, compounds 9i, 7d, 9h, 9o, 9g, and 9e showed potent activity with IC50 values in the range of 11.1-17.8 µM. Whereas for hCA-II, compounds 9i, 9c, 9o, and 9j showed great potential with IC50 values in the range of 10.9-18.5 µM. The preliminary structure-activity relationship indicates that the presence of the 1H-1,2,3-triazole moiety in those synthesized 1H-1,2,3triazole analogs (7a-7d and 9a-9s) significantly contributes to the overall activity. However, several substitutions on this scaffold affect the activity to several folds. The selectivity index showed that compounds 9c, 9k, and 9p are selective inhibitors of hCA-II. Kinetics studies showed that these compounds inhibited both enzymes (bCA-II and hCA-II) in a competitive manner. Molecular docking indicates that all the active compounds fit well in the active site of CA-II. This study has explored the role of 1H-1,2,3-triazole-containing compounds in the inhibition of CA-II to combat CA-II-related disorders.

A series of 1H-1,2,3-triazole analogs (7a-7d and 9a-9s) were synthesized via "click" chemistry and evaluated for in vitro carbonic anhydrase-II (bovine and human) inhibitory activity. The synthesis of intermediates, 7a and 7c, was achieved by using (S)-(-)ethyl lactate as a starting material. These compounds (7a and 7c) underwent Suzuki-Miyaura cross-coupling reaction with different arylboronic acids in 1,4-dioxane, reflux at 90-120 °C for 8 h using Pd(PPh 3 ) 4 as a catalyst (5 mol%), and K 2 CO 3 (3.0 equiv)/K 2 PO 4 (3.0 equiv) as a base to produce target 1H-1,2,3-triazole molecules (9a-9s) for a good yield of 67-86%. All the synthesized compounds were characterized through NMR spectroscopic techniques. Furthermore, all those compounds have shown significant inhibitory potential for both sources of carbonic anhydrase-II (CA-II). In the case of bCA-II, compounds 9i, 7d, 9h, 9o, 9g, and 9e showed potent activity with IC50 values in the range of 11.1-17.8 µM. Whereas for hCA-II, compounds 9i, 9c, 9o, and 9j showed great potential with IC50 values in the range of 10.9-18.5 µM. The preliminary structure-activity relationship indicates that the presence of the 1H-1,2,3-triazole moiety in those synthesized 1H-1,2,3triazole analogs (7a-7d and 9a-9s) significantly contributes to the overall activity. However, several substitutions on this scaffold affect the activity to several folds. The selectivity index showed that compounds 9c, 9k, and 9p are selective inhibitors of hCA-II. Kinetics studies showed that these compounds inhibited both enzymes (bCA-II and hCA-II) in a competitive manner. Molecular docking indicates that all the active compounds fit well in the active site of CA-II. This study has explored the role of 1H-1,2,3-triazole-containing compounds in the inhibition of CA-II to combat CA-II-related disorders.

A series of 1H-1,2,3-triazole analogs (7a-7d and 9a-9s) were synthesized via "click" chemistry and evaluated for in vitro carbonic anhydrase-II (bovine and human) inhibitory activity. The synthesis of intermediates, 7a and 7c, was achieved by using (S)-(-)ethyl lactate as a starting material. These compounds (7a and 7c) underwent Suzuki-Miyaura cross-coupling reaction with different arylboronic acids in 1,4-dioxane, reflux at 90-120 °C for 8 h using Pd(PPh 3 ) 4 as a catalyst (5 mol%), and K 2 CO 3 (3.0 equiv)/K 2 PO 4 (3.0 equiv) as a base to produce target 1H-1,2,3-triazole molecules (9a-9s) for a good yield of 67-86%. All the synthesized compounds were characterized through NMR spectroscopic techniques. Furthermore, all those compounds have shown significant inhibitory potential for both sources of carbonic anhydrase-II (CA-II). In the case of bCA-II, compounds 9i, 7d, 9h, 9o, 9g, and 9e showed potent activity with IC50 values in the range of 11.1-17.8 µM. Whereas for hCA-II, compounds 9i, 9c, 9o, and 9j showed great potential with IC50 values in the range of 10.9-18.5 µM. The preliminary structure-activity relationship indicates that the presence of the 1H-1,2,3-triazole moiety in those synthesized 1H-1,2,3triazole analogs (7a-7d and 9a-9s) significantly contributes to the overall activity. However, several substitutions on this scaffold affect the activity to several folds. The selectivity index showed that compounds 9c, 9k, and 9p are selective inhibitors of hCA-II. Kinetics studies showed that these compounds inhibited both enzymes (bCA-II and hCA-II) in a competitive manner. Molecular docking indicates that all the active compounds fit well in the active site of CA-II. This study has explored the role of 1H-1,2,3-triazole-containing compounds in the inhibition of CA-II to combat CA-II-related disorders.

A bicyclic unsaturated 1,2-diol framework was found to undergo an interesting set of domino reactions on treatment with oxidants. One-pot syntheses of seven-membered-ringcontaining frameworks were achieved by a Pb(OAc) 4 -mediated domino process, while with other oxidants investigated, such as Mn(OAc) 3 , Dess-Martin periodinane, PhI(OAc) 2 , Ph 3 Bi(CO) 3 , NaIO 4 , and NaBiO 3 , the domino process was interrupted halfway through. Finally, tetrapropylammonium perruthenate (TPAP-NMO), Pd(OAc) 2 , pyridinium dichromate (PDC), and pyridinium chlorochromate (PCC) gave only allylic oxidation and further diketone formation without any of the bond cleavage that is necessary to initiate the domino [a]

A bicyclic unsaturated 1,2-diol framework was found to undergo an interesting set of domino reactions on treatment with oxidants. One-pot syntheses of seven-membered-ringcontaining frameworks were achieved by a Pb(OAc) 4 -mediated domino process, while with other oxidants investigated, such as Mn(OAc) 3 , Dess-Martin periodinane, PhI(OAc) 2 , Ph 3 Bi(CO) 3 , NaIO 4 , and NaBiO 3 , the domino process was interrupted halfway through. Finally, tetrapropylammonium perruthenate (TPAP-NMO), Pd(OAc) 2 , pyridinium dichromate (PDC), and pyridinium chlorochromate (PCC) gave only allylic oxidation and further diketone formation without any of the bond cleavage that is necessary to initiate the domino [a]

The aroma composition of autoxidized arachidonic acid was characterized by aroma extract dilution analysis. The most potent odorant was trans-4,5-epoxy-(E)-2-decenal followed by 1-octen-3-one, (E,Z)-2,4-decadienal, (E,Z,Z)-2,4,7-tridecatrienal, (E,E)-2,4-decadienal, and hexanal. (E,Z,Z)-2,4,7-Tridecatrienal was unequivocally identified by mass spectrometry and nuclear magnetic resonance (NMR) data. The stereochemistry of its extended double-bond system was elucidated on the basis of NMR measurements. The target compound was synthesized in four steps starting with bromination of 2-octyn-1-ol, followed by copper-catalyzed coupling of the bromide with ethylmagnesium bromide and (E)-2-penten-4-yn-1-ol. Partial hydrogenation of the resulting C 13 -compound with triple bonds in the positions C-4 and C-7 gave rise to (E,Z,Z)-2,4,7-tridecatrien-1-ol, which was finally oxidized to the target compound. It exhibits a typical egg-white-like, marine-like odor at low concentrations, and an intense orange-citrus, animal-like odor at higher concentrations. Its odor threshold was estimated by gas chromatography-olfactometry to be 0.07 ng/L air, which is of the same order of magnitude as that reported for 1-octen-3-one and (E,E)-2,4-decadienal.

Centaurea asutro-anatolica Hub.-Mor. and C. kizildaghensis Uzunh., E. Doğan & H. Duman, two indigenous perennial herbs from the Turkish flora, belong to the medicinally important genus Centaurea L. (fam: Asteraceae), which comprises ca. 600 species worldwide. While various Centaurea species are well-known for producing alkaloids, flavonoids, lignans and terpenoids, there is no report on any thorough phytochemical work on any of these two species available to date. In continuation of our phytochemical and bioactivity studies on the Turkish Centaurea species, four flavonoids apigenin (1), apigenin 7,4'-dimethyl ether (2), genkwanin (3) and quercetin (4) were isolated from the methanol extracts of the aerial parts of C. austro-anatolica and C. kizildaghensis, for the very first time. The structures of the flavonoids were elucidated conclusively by spectroscopic means, i.e., UV, MS and 1D and 2D NMR data analyses. The distribution of these flavonoids (1-4) within the genus Centaurea and their possible chemotaxonomic implications within the genus Centaurea or the family Asteraceae have been discussed.

Centaurea asutro-anatolica Hub.-Mor. and C. kizildaghensis Uzunh., E. Doğan & H. Duman, two indigenous perennial herbs from the Turkish flora, belong to the medicinally important genus Centaurea L. (fam: Asteraceae), which comprises ca. 600 species worldwide. While various Centaurea species are well-known for producing alkaloids, flavonoids, lignans and terpenoids, there is no report on any thorough phytochemical work on any of these two species available to date. In continuation of our phytochemical and bioactivity studies on the Turkish Centaurea species, four flavonoids apigenin (1), apigenin 7,4'-dimethyl ether (2), genkwanin (3) and quercetin (4) were isolated from the methanol extracts of the aerial parts of C. austro-anatolica and C. kizildaghensis, for the very first time. The structures of the flavonoids were elucidated conclusively by spectroscopic means, i.e., UV, MS and 1D and 2D NMR data analyses. The distribution of these flavonoids (1-4) within the genus Centaurea and their possible chemotaxonomic implications within the genus Centaurea or the family Asteraceae have been discussed.

3D molecular structure determination is a challenge for organic compounds or natural products available in minute amounts. Proton/proton and proton/carbon correlations yield the constitution. J couplings and NOEs oftentimes supported by one-bond 1 H, 13 C residual dipolar couplings (RDCs) or by C residual chemical shift anisotropies (RCSAs) provide the relative configuration. However, these RDCs or carbon RCSAs rely on 1% natural abundance of 13 C preventing their use for compounds available only in quantities of a few 10's of µgs. By contrast, 1 H RCSAs provide similar information on spatial orientation of structural moieties within a molecule, while using the abundant 1 H spin. Herein, 1 H RCSAs are accurately measured using constrained aligning gels or liquid crystals and applied to the 3D structural determination of molecules with varying complexities. Even more, deuterated alignment media allow the elucidation of the relative configuration of around 35 µg of a briarane compound isolated from Briareum asbestinum.

Irradiation of a substituted ansa-titanocene(IV) dihydroxido complex with visible light induces Ti-O bond dissociation. In contrast to previous studies on structurally similar unbridged complexes, no side reactions are observed and formation of the Ti(III) species is highly selective. The formation of OH radicals was proved using a biradicaloid species.

Anthocephalusine A (1) and 3β‐isodihydrocadambine 4‐oxide (2) were isolated from the leaves of Anthocephalus chinensis (Rubiaceae), together with five known compounds. The structures were established by spectroscopic methods including 2D‐NMR analyses.

p-Cholorosulfinylaniline was prepared by the reaction of p-chloroaniline and SOCl2. The structural, conformational and configurational properties of the obtained liquid compound were studied by Raman and infrared spectroscopy in the liquid state. The assignment of the vibrational spectra was carried out with the help of data obtained by quantum chemical calculations at the harmonic oscillator approximation and using anharmonic vibrational self-consistent field (VSCF) method as well. The 1H and 13C NMR chemical shifts of the molecule were calculated by Gauge including orbital (GIAO) method (DFT/B3LYP approximation using 6-311 + G (df), 6-311++G (df,pd) and cc-pVTZ basis sets) and compared to the experimental values. Natural Bond Orbital analysis provides an explanation of the stability of the molecule and its electronic properties upon charge delocalization.

The enzyme type 5 17β-hydroxysteroid dehydrogenase 5 (17β-HSD5) catalyzes the transformation of androstenedione (4-dione) to testosterone (T) in the prostate. This metabolic pathway remains active in cancer patients receiving androgen deprivation therapy. Since physicians seek to develop advantageous and better new treatments to increase the average survival of these patients, we synthesized several different dehydroepiandrosterone derivatives. These compounds have a pyrazole or imidazole function at C-17 and an ester moiety at C-3 and were studied as inhibitors of 17β-HSD5. The kinetic parameters of this enzyme were determined for use in inhibition assays. Their pharmacological effect was also determined on gonadectomized hamsters treated with Δ4-androstenedione (4-dione) or testosterone (T) and/or the novel compounds. The results indicated that the incorporation of a heterocycle at C-17 induced strong 17β-HSD5 inhibition. These derivatives decreased flank organ diameter and prosta...

The tetrapyrrolic chlorophyllc atabolites (or phyllobilins, PBs) were analyzed in yellow fall leaveso ft he grape Chardonnay,acommon Vitis vinifera white wine cultivar.T he major fractionsi nl eaf extractso fV. vinifera,t entatively assigned to PBs, were isolated andt heir structures elucidated. The dominant fractioni sadioxobilin-typen on-fluorescent Chl-cataboliteo fapreviously observedt ype. Twol ess polar fluorescent PBs were characterized as an ovel dioxobilintype fluorescent Chl-catabolite with ab icyclo-1',6'-glycosyl architecture, and its new fluorescent formyloxobilin-type analogue. The discovery of persistenth ypermodified fluorescent PBs with the architectureo fb icyclo-[17.3.1]-PBs (bcPBs), suggestst he activity of an unknown enzyme that forges the 20-memberedm acroring at the tetrapyrrolic core of af luorescent PB. bcPBsm ay play specificp hysiological roles in grapevine plants and represent endogenous anti-infective agents, as found similarly for other organicb icyclo-[n.3.1]-1',6'-glycosyl derivatives.

Synthesis of a series of the substituted [(pyridinyl and pyrimidin-2-ylimino)-ethyl]-4hydroxy-chromen-2-ones and their tetrazole derivates is presented in this study. By catalytic condensation of 4-hydroxy-3-acetylcoumarine 2 and 2-aminopyridines 3(a-d), 3-[(pyridin-2-ylimino)ethyl]-4-hydroxy-chromen-2-ones 4(a-d) are synthesized in high yield. During the condensation reaction of 2 and 4-amino-2,6-dihydroxypyrimidine 3e, 3-[1-(2,6-Dihydroxy-pyrimidin-4-ylimino)ethyl]-4-hydroxy-chromen-2-one 4e as condensation products is synthesized. In following series, by cyclization reactions of compounds 4 (a-e) with sodium azide, analogue 3-substituted pyridin-2-yl and pyrimidin-2-yl-5-methyl-2,5-dihydro-1H-tetrazol-5-yl]-4-hydroxy-chromen-2-one 5(a-e) are synthesized the products. Structural characterization of the synthesized products is done on the basis of spectrometric data. Antibacterial activity of the compounds 4(a-e) and 5(a-e) against S. aureus, E. coli and Klebsiella was examined by measuring the inhibition zones around the disks marked with the corresponding products solution. The impact of substitutions in antimicrobial is also explored. Compounds with polar groups have shown significant antibacterial activity against these microorganisms.

Sea cucumbers produce numerous compounds with a wide range of chemical structural diversity. Among these, saponins are the most diverse and include sulfated, non-sulfated, acetylated and methylated congeners with different aglycone and sugar moieties. In this study, MALDI and ESI tandem mass spectrometry, in the positive ion mode, were used to elucidate the structure of new saponins extracted from the viscera of H. lessoni. Fragmentation of the aglycone provided structural information on the presence of the acetyl group. The presence of the O-acetyl group was confirmed by observing the mass transition of 60 u corresponding to the loss of a molecule of acetic acid. Ion fingerprints from the glycosidic cleavage provided information on the mass of the aglycone (core), and the sequence and type of monosaccharides that constitute the sugar moiety. The tandem mass spectra of the saponin precursor ions [M + Na] + provided a wealth of detailed structural information on the glycosidic bond cleavages. As a result, and in conjunction with existing literature, we characterized the structure of five new acetylated saponins,

Background The escalating global challenge of antibiotic resistance severely restricts our ability to treat common infectious diseases, necessitating the urgent need for the development of novel antibiotics with distinct mechanisms of action. Actinobacteria, a diverse group of bacteria with medical, industrial, pharmaceutical, and ecological significance, produce approximately two-thirds of clinically used antibiotics. Endophytic actinobacteria (EA), residing within various plant species, represent a promising source for discovering novel antibiotics to combat this raising threat. This study aimed to explore the diversity and antibacterial characteristics of EA isolated from Mentha longifolia and Lonicera nummulariifolia, leveraging the host specificity and adaptation of EA to different plant species. Healthy plant samples were surface-sterilized and cultured on four distinct isolation media. Results Nine EA isolates were identified from the roots, stems, and leaves of the plants based on morphological and molecular characterization. These isolates were taxonomically classified into two different families, Nocardiaceae and Streptomycetaceae, with Streptomyces being the dominant genus. All strains, except KUMS-B13, were reported as endophytes for the first time. Among the isolates, KUMS-B9 showed 98.66% sequence similarity to its closest relative strain, classifying it as a potential rare novel strain. The isolates exhibited diverse spore morphologies, including cylindrical, cubic, biconvex, oval, or ovoid shapes, with smooth or wrinkled surfaces. Six of the nine isolates displayed antibacterial activity against at least one of the tested bacteria: Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus. Isolate KUMS-B11, closely related to Streptomyces flavogriseus, showed broad-spectrum inhibition against all tested bacteria. Notably, a majority of the isolates demonstrated antagonistic activity against P. aeruginosa. Conclusions This study highlights EA isolated from Mentha longifolia and Lonicera nummulariifolia as a valuable source of medically bioactive metabolites with potential applications in human health. The isolation of new EA presents a promising approach to discovering novel therapeutic agents from unexplored ecological niches to battle antibiotic resistance. Furthermore, these findings emphasize the potential of plant-symbiotic bacteria in producing bioactive compounds with significant medicinal, pharmaceutical, and biotechnological applications.

Tetraamminecopper perchlorate (TACP) is one of the most interesting explosive copper perchlorate-ammonia complexes. Despite the fact that this complex has been known for more than 100 years there is very little information in the literature about its detonation parameters. Impact sensitivity of TACP is slightly higher than that for PETN while friction sensitivity is between those for PETN and RDX. Detonation velocity for infinite diameter is 3230 m s À 1 (density 0.9 g cm À 3 ). Critical diameter of TACP is low -less than 2 mm. Based on the heat of combustion measurement the previously published erroneous enthalpy of formation was corrected to À 496 kJ mol À 1 . Detonation heat of TACP is 4322 kJ kg À 1 and Gurney velocity is 1536 m s À 1 . Experimentally measured detonation parameters of TACP were also compared with theoretically calculated values by the EXPLO5 code.

The palatability of various organs (body wall, cuvierian gland, viscera, longitudinal muscle bands and gonads) of sea cucumber Holothuria leucospilota (Brandt) was studied by feeding experiments, performed on a freshwater fish Sarotherodon mossambicus and a marine fish Theraponjarbua. The result shows that the food pellets of the body wall were less toxic and more palatable than the gonads, viscera and cuvierian gland (p<O.OOI).

Forced degradation studies are an essential component of pharmaceutical development, designed to intentionally degrade drug substances and products under conditions more rigorous than standard accelerated conditions. These studies play a pivotal role in validating the specificity of stability-indicating analytical methods. By exposing drug substances to various stress conditions, forced degradation reveals degradation pathways and identifies degradation products, providing critical insights into the molecular stability and chemical behavior of active pharmaceutical ingredients. These insights are instrumental in guiding formulation design, packaging development, and shelf-life determination. However, despite its significance, regulatory guidelines on forced degradation often lack comprehensive instructions, leaving the execution and interpretation of these studies to the discretion of researchers. This review aims to address this gap by providing a systematic examination of forced degradation methodologies, elucidating degradation mechanisms, and summarizing analytical techniques integral to stability-indicating method development. Additionally, it highlights current trends and challenges in forced degradation research, contributing to the advancement of robust and reliable analytical approaches in pharmaceutical science.