Stable Derivatives Research Articles

Mechanical trapping and in situ derivatization of the porphodimethene intermediate

Manipulation of the energy profile of a chemical reaction plays a crucial role in modulating its progress and selectivities. Porphodimethene and phlorin are two key isoelectronic intermediates during the stepwise oxidation process leading to the formation of porphyrin from calix[4]pyrrole. We report here the mechanical capture of porphodimethene instead of phlorin as well as its simultaneous derivatization by means of molecular-strain engineering (MSE). By tuning the linker between its 5- and 15-meso-positions, a constrained porphodimethene has been trapped which can be oxidized with 4,5-dichloro-3,6-dioxo-1,2-benzenedinitrile in the presence of a range of nucleophiles to afford a novel class of stable disubstituted porphodimethene derivatives. Their structures were characterized by NMR spectroscopies, mass spectrometry, and single-crystal X-ray crystallography. Theoretical calculations indicate that the enhanced strain energy resulted from the elongation of the bow-limb in the proposed porphyrin bow favors the formation of the configuration of the porphodimethene intermediate containing two sp3-hybridized meso-carbons rather than that of the phlorin consisting of one sp3-meso-carbon atom. This work demonstrates that MSE can steer the reaction trajectory through specific intermediates, providing the ability to control precisely the reaction progress and selectivity of desired products.

Environment-Friendly Catalytic Mineralization of Phenol and Chlorophenols with Cu- and Fe- Tetrakis(4-aminophenyl)-porphyrin—Silica Hybrid Aerogels

Fenton reactions with metal complexes of substituted porphyrins and hydrogen peroxide are useful tools for the mineralization of environmentally dangerous substances. In the homogeneous phase, autooxidation of the prophyrin ring may also occur. Covalent binding of porphyrins to a solid support may increase the lifetime of the catalysts and might change its activity. In this study, highly water-insoluble copper and iron complexes of 5,10,15,20-tetrakis(4-aminophenyl)porphyrin were synthesized and bonded covalently to a very hydrophilic silica aerogel matrix prepared by co-gelation of the propyl triethoxysilyl-functionalized porphyrin complex precursors with tetramethoxysilane, followed by a supercritical carbon dioxide drying. In contrast to the insoluble nature of the porphyrin complexes, the as-prepared aerogel catalysts were highly compatible with the aqueous phase. Their catalytic activities were tested in the mineralization reaction of phenol, 3-chlorophenol, and 2,4-dichlorophenol with hydrogen peroxide. The results show that both aerogels catalyzed the oxidation of phenol and chlorophenols to harmless short-chained carboxylic acids under neutral conditions. In batch experiments, and also in a miniature continuous-flow tubular reactor, the aerogel catalysts gradually reduced their activity, due to the slow oxidation of the porphyrin ring. However, the rate and extent of the degradation was moderate and did not exclude the possibility that the as-prepared catalysts, as well as their more stable derivatives, might find practical applications in environment protection.

Analytical covariance estimation for iterative CT reconstruction methods

Covariance of reconstruction images are useful to analyze the magnitude and correlation of noise in the evaluation of systems and reconstruction algorithms. The covariance estimation requires a big number of image samples that are hard to acquire in reality. A covariance propagation method from projection by a few noisy realizations is studied in this work. Based on the property of convergent points of cost funtions, the proposed method is composed of three steps, (1) construct a relationship between the covariance of projection and corresponding reconstruction from cost functions at its convergent point, (2) simplify the covariance relationship constructed in (1) by introducing an approximate gradient of penalties, and (3) obtain an analytical covariance estimation according to the simplified relationship in (2). Three approximation methods for step (2) are studied: the linear approximation of the gradient of penalties (LAM), the Taylor apprximation (TAM), and the mixture of LAM and TAM (MAM). TV and qGGMRF penalized weighted least square methods are experimented on. Results from statistical methods are used as reference. Under the condition of unstable 2nd derivative of penalties such as TV, the covariance image estimated by LAM accords to reference well but of smaller values, while the covarianc estimation by TAM is quite off. Under the conditon of relatively stable 2nd derivative of penalties such as qGGMRF, TAM performs well and LAM is again with a negative bias in magnitude. MAM gives a best performance under both conditions by combining LAM and TAM. Results also show that only one noise realization is enough to obtain reasonable covariance estimation analytically, which is important for practical usage. This work suggests the necessity and a new way to estimate the covariance for non-quadratically penalized reconstructions. Currently, the proposed method is computationally expensive for large size reconstructions.Computational efficiency is our future work to focus.

A New PEDOT Derivative for Efficient Organic Solar Cell with a Fill Factor of 0.80

AbstractAlthough PEDOT:PSS is the most prominently used conducting polymer as hole transporting layer (HTL) material in organic solar cells (OSCs), the strong acidity of PEDOT:PSS has been proved to cause corrosion on electrodes, which is largely responsible for device instability. At present, the development of a non‐corrosive and stable PEDOT with comparable performance to PEDOT:PSS remains a great challenge in the field. Herein, a solid n‐PEDOT:POM powder with neutral pH is synthesized by utilizing polyoxometalate (POM) as an oxidizing reagent, which exhibits excellent water solubility, high chemical stability, and superior hole collection ability. Impressively, an amazing fill factor of 0.80 along with a photovoltaic efficiency of 17.62% is obtained in the OSC by using n‐PEDOT:POM as the HTL, suggesting an exceptional hole collection ability for n‐PEDOT:POM. In addition, the neutral pH of PEDOT:PSS effectively improves the long‐term stability of OSCs. X‐ray photoelectron spectroscopy results reveal that, compared to the electrode/PEDOT:PSS interface, the permeation of dissociative indium from the electrode to n‐PEDOT:POM can be greatly retarded, which proves the non‐corrosive effect of n‐PEDOT:POM and its improvement of device stability. The successful preparation of a non‐corrosive and stable PEDOT derivative without sacrificing its hole collection ability provides the most fruitful new insight into developing high‐performance HTL materials.

Nitrites as precursors of N-nitrosation in pharmaceutical samples – A trace level analysis

The ultra-performance liquid chromatography (UPLC) method, which involves pre-column derivatization of nitrite with 2,3-diaminonaphthalene (DAN) to form 2,3-naphthotriazole (NAT), offers the advantages of easy sample preparation, simple derivatization, stable derivatives, rapid analysis, high sensitivity and specificity and lack of interferences for determining nitrite in pharmaceutical samples. Determination of NAT was performed on a an Acquity UPLC HSS T3 column using a gradient elution of 0.1% formic acid with acetonitrile at flow rate of 0.4 mL/min and temperature at 45 °C. The single-quadrupole mass detector was operated in the positive ion mode. Quadrupole mass analyser was employed in selected ion monitoring mode using a target ion at m/z = 170 as [M+H]+. The UPLC-MS method was validated as per International Council on Harmonization (ICH) guidelines in terms of linearity, limit of detection, limit of quantification, selectivity, accuracy, precision, intermediate precision and stability. The UPLC-MS method was demonstrated to be applicable for the determination of nitrite in various pharmaceutical samples. The proposed UPLC-MS method was used to study the effect of nitrite content in pharmaceutical products on the formation of N-nitrosamines. The high importance of nitrites in relation to the N-nitrosation reaction was discussed. As deduced from theory and justified by the presented results, reducing the nitrite concentration could definitely solve the N-nitrosamine contamination. Nitrites, unlike secondary and tertiary amines, are universal precursors to any N-nitrosamine, so this solution is easily transferable to any relevant pharmaceutical product.

Immobilization of Eversa Lipases on Hydrophobic Supports for Ethanolysis of Sunflower Oil Solvent-Free

Lipases are an important group of biocatalysts for many industrial applications. Two new commercial low-cost lipases Eversa® Transform and Eversa® Transform 2.0 was immobilized on four different hydrophobic supports: Lewatit-DVB, Purolite-DVB, Sepabeads-C18, and Purolite-C18. The performance of immobilized lipases was investigated in the transesterification of sunflower oil solvent-free in an anhydrous medium. Interesting results were obtained for both lipases and the four supports, but with Sepabeads support the lipases Eversa showed high catalytic activity. However, the more stable and efficient derivative was Eversa® Transform immobilized on Sepabeads C-18. A 98 wt% of ethyl ester of fatty acid (FAEE) was obtained, in 3 h at 40ºC, ethanol/sunflower oil molar ratio of 3:1 and a 10 wt% of the immobilized biocatalyst. After 6 reaction cycles, the immobilized biocatalyst preserved 70 wt% of activity. Both lipases immobilized in Sepabeads C-18 were highly active and stable in the presence of ethanol. The immobilization of Eversa Transform and Eversa Transform 2.0 in hydrophobic supports described in this study appears to be a promising alternative to the immobilization and application of these news lipases still unexplored.

Virtual screening and molecular dynamic simulations of the antimalarial derivatives of 2-anilino 4-amino substituted quinazolines docked against a Pf-DHODH protein target

BackgroundThe processes of drug development and validation are too expensive to be subjected to experimental trial and errors. Hence, the use of the insilico approach becomes imperative. To this effect, the drug-likeness and pharmacokinetic properties of the ten (10) previously designed derivatives of 2-anilino 4-amino substituted quinazolines were carried out. Their predicted ligand binding interactions were also carried out by docking them against the Plasmodium falciparum dihydroorotate dehydrogenase (Pf-DHODH) protein target, and the stability of the complex was determined through dynamic simulations. The drug-likeness and pharmacokinetic characteristics were estimated using the online SwissADME software, while the Molegro Virtual Docker (MVD) software was used for molecular docking. And the dynamic simulation was performed for the duration of 100 ns to verify the stability of the docked complex, with the aid of a Schrödinger program, Desmond.ResultsThe designed derivatives were all found to pass the Lipinski test of drug likeness, while the pharmacokinetic studies result that the skin permeability and molar refractivity values of the derivatives are both within the limits. In addition, except for derivative C-01, most of the derivatives have strong gastrointestinal absorptions and lack Pgp substrate. Furthermore, no derivative inhibited CYP1A2, CYP2C9, or CYP2C19. The docking studies show the better binding affinities between the ligands and Pf-DHODH than those between the atovaquone or chloroquine standards. The derivative C-02, {5-((6,7-dimethoxy-4-((3-nitrobenzyl)amino)quinazolin-2-yl)amino)-2-fluorobenzaldehyde} was found to be the most stable derivative, with a re-rank docking score of − 173.528 kcal/mol and interaction energy of − 225.112 kcal/mol. The dynamic simulation analysis shows that the derivative C-02 forms a stable complex with the protein target over the simulation time.ConclusionsThe ability of these ligands to form hydrogen bonds, as well as various other interactions, was cited as a factor responsible for their better binding affinity. These findings could aid further the development of enhanced antimalarial drugs.

2‐Quinolyl Benzodiazaborine: A Tunable Platform for Aggregation‐Induced Emission Luminogens via Formation of Dimeric Borate Crystals with Acid Additives

Abstract2‐Quinolyl benzodiazaborine (DAB) was synthesized and its conversion to a borate species was investigated. Addition of carboxylic acids and hydrogen fluoride led to facile formation of a stable borate derivative, whose structure was unambiguously characterized by single crystal X‐ray diffraction analysis. The borates show intense aggregation‐induced emission (AIE) in crystals, which is thought to be derived from a rigid dimeric structure with intermolecular hydrogen bonding.

Biocidal properties investigation of the new guanidine-containing alkoxysilanes and siloxanes and epoxy materials modified by them

This article presents a synthesis of stable guanidine-containing alkoxysilyl derivatives based on the synthesis procedure through amino derivatives and ylide of thiourea suggested previously. Amino- and mercapto-containing siloxane oligomers were synthesized by hydrolytic co-condensation based on the silanes thus obtained, and the biocidal activity of their aqueous solutions in comparison with the starting monomers was studied. The prospects of using the resulting compounds as biocidal additives to epoxy compositions and a high biocidal activity at their small concentrations in the cured material against S. aureus, E. coli, and C. albicans strains were demonstrated.

The Fischer-Tropsch synthesis: A few enduring mechanistic conundrums revisited

Owing to their extra-large pores compared to traditional aluminosilicate zeolites, silicogermanates could be attractive for the catalytic transformation of bulky molecules, provided the frameworks can be modified to incorporate acid sites and can be stabilized to survive calcination. Post-synthetic isomorphic substitution of Ge by Si and Al would present a route to achieve this goal. This report describes the transformation and characterization of the non-stable IM-12 silicogermanate into a new stable IZM-7 aluminosilicogermanate by partially substituting Ge by Si in gaseous form to stabilize the material, followed by an aqueous alumination step. IZM-7-based catalyst presents promising performance in the hydroconversion of n-decane compared to conventional zeolites, opening perspectives for the catalytic use of stable derivatives of silicogermanate zeolites.

High Pressure Liquid Chromatography Identification and Quantification of Morpholine Residual Content in Cobicistat After Derivatization

A derivatization HPLC procedure has been developed to identify and enumerate morpholine (MPE) in cobicistat (CCT) pharmaceutical active substances. MPE react with acetonitrile solution of 1-Naphthyl isothiocyanate to produce stable MPE derivative. The MPE derivative produced was identified and enumerated by HPLC based procedure. The linearity range of MPE was 0.3002675–1.201070 μg/mL with good squared correlation (0.9995), and limits of detection and quantification were 0.1000 μg/mL and 0.3001 μg/mL, respectively. Low (50% of specification quantity), medium (100% of specification quantity), and high (150% of specification quantity) concentrations of MPE were added in CCT samples to evaluate recovery rate. The added recovery rate ranged from 97.9% to 100.4%. The precision value was 0.79% relative standard deviation. The developed procedure also has good selectivity and robustness. This quantitative procedure for MPE can successfully be implemented to analyse the MPE residual quantities in CCT pharmaceutical active substances.

Theoretical investigation of substituent effects on the relative stabilities and electronic structure of [BnXn]2- clusters.

In this study, we provide a theoretical evaluation of relative stabilities and electronic structure for [BnXn]2- clusters (n = 10, 12, 13, 14, 15, 16). Structural and electronic characteristics of [BnXn]2- clusters are examined by comparison with the [B12X12]2- counterparts with a focus on the substituent effects (X = H, F, Cl, Br, CN, BO, OH, NH2) on the electronic structure, electron detachment energies, formation enthalpies, and charge distributions. For the electronic structure and electron detachment energies, substituent effects on boron clusters are shown to follow a very similar trend to the mesomeric and inductive effects (± M and ± I) of π-conjugated systems, and the most stable derivatives in terms of HOMO/LUMO and electron detachment energies are calculated for CN and BO substituents due to strong -M effects. In the case of formation enthalpies for larger boron clusters (n ≥ 13), the icosahedral barrier is shown to increase with the halogen and CN substitution, whereas it is possible to reduce the icosahedral barrier for the cases of X = OH and NH2. It is shown that this reduction results from destabilizing the [B12X12]2- cluster with electronic (+ M) and symmetry effects induced by OH and NH2 ligands.

Radionuclide-labeled boron delivery agents

<p indent="0mm">Boron neutron capture therapy (BNCT), as a duality radiotherapy method that combines neutron irradiation and boron-containing targeted drugs, has attracted much attention. The successful BNCT mainly depends on three aspects: (1) Ideal boron delivery agents, (2) reasonable neutron source, and (3) accurate dose measurement system. Therefore, it is very important to realize the rapid and accurate measurement of the boron concentration in the patient. There are a variety of methods that have been used to measure the boron concentration. The indirect measurement method often requires the blood/tissue sample, so it can only give an estimate of the boron concentration at a single time point and sampling point, but cannot accurately describe the biodistribution of ¹⁰B concentration and the boron concentration ratio between target and non-target tissues. The sensitivity of magnetic resonance imaging (MRI) is poor, while radionuclide imaging is a non-invasive method and can provide the distribution of boron delivery agents <italic>in vivo</italic>. This article briefly describes the existing methods of measuring the boron concentration in BNCT, and the progress of radionuclide (¹⁸F, ¹²⁵I/¹³¹I, and ^99mTc) labeling methods of boron delivery agents (such as 4-borono-<italic>L</italic>-phenylalanine (BPA) and disodium mercaptoundecahydrododecaborate (BSH)) for radionuclide imaging. The common methods for labeling boron delivery agents with ¹⁸F are [¹⁸F]F₂ electrophilic substitution with a carrier, [¹⁸F]F⁻ nucleophilic substitution without a carrier, and isotope exchange. ¹⁸F-labeled BPA ([¹⁸F]-FBPA) was first prepared by the electrophilic substitution method. Research has shown that BPA and [¹⁸F]-FBPA had similar pharmacokinetics and biodistribution results. Although electrophilic fluorination can yield [¹⁸F]-FBPA with high radiochemical purity, the overall yield of the reaction is low, and the [¹⁸F]F₂ used in this process is relatively active and highly corrosive. The effect of stable F₂ gas carrier on the reaction cannot be ignored, which makes the specific activity of the product lower and the imaging quality worse. [¹⁸F]-FBPA can also be obtained from the high-value iodine-ylide precursors by nucleophilic fluoridation reaction. This method has a short labeling time and high specific activity. Fluoroboronotyrosine (FBY), a metabolically stable boron-tyrosine derivative, can also be used as a boron delivery agent, and [¹⁸F]-FBY has been prepared easily and quickly with a high radiochemical yield and radiochemical purity by isotope exchange as a tumor-targeting PET imaging agent. [¹⁸F]-FBY was stable <italic>in vitro</italic>, and it had the highest uptake in tumor and low uptake in normal tissue in mice with cutaneous melanoma grafts. The boron delivery agents of nested and closed carboranes can be radioiodine-labeled using N-chlorosuccinimide (NCS) as oxidant by electrophile iodization reaction at room temperature for <sc>10−30 min,</sc> the radiochemical yield was basically above 70%. Radioiodine-labeled carborane derivatives can also be achieved using isotope exchange reactions under catalytic conditions, but they had a lower specific activity. Unfortunately, as for the radioiodine-labeled carborane compounds, most studies only described the labeling method without further <italic>in vivo</italic> experimental data. [^99mTc(CO)₃]⁺-labeled carboranes have been prepared in aqueous solution in the presence of potassium fluoride under mild conditions, but no further biological experiments were conducted. ^99mTc-labeled BPA (^99mTc-DMG-BPA) was also obtained. Biodistribution result showed that the complex was selectively enriched in the tumor and cleared faster in non-target tissues, but unfortunately, its uptake in liver and kidney was relatively high, which may affect tumor imaging. In conclusion, radionuclide-labeled boron delivery agents are still in their infancy, and there are many aspects that need to be considered, such as radionuclide (half-life and decay type), radionuclide labeling position (influence on the biological activity of the boron delivery agent), labeling method (nucleophilic substitution, electrophilic substitution, isotope exchange, and coordination chemistry), the stability of the labeled compound and its influencing factors, and the administration method and time, etc.

Joseph R. Bertino: In Memoriam (1930–2021)

Joseph R. Bertino: In Memoriam (1930–2021)

IZM-7: A new stable aluminosilicogermanate with a promising catalytic activity

Owing to their extra-large pores compared to traditional aluminosilicate zeolites, silicogermanates could be attractive for the catalytic transformation of bulky molecules, provided the frameworks can be modified to incorporate acid sites and can be stabilized to survive calcination. Post-synthetic isomorphic substitution of Ge by Si and Al would present a route to achieve this goal. This report describes the transformation and characterization of the non-stable IM-12 silicogermanate into a new stable IZM-7 aluminosilicogermanate by partially substituting Ge by Si in gaseous form to stabilize the material, followed by an aqueous alumination step. IZM-7-based catalyst presents promising performance in the hydroconversion of n-decane compared to conventional zeolites, opening perspectives for the catalytic use of stable derivatives of silicogermanate zeolites.

Corroles: The Hitherto Elusive Parent Macrocycle and its Metal Complexes.

Corroles, macrocycles that owe their name to the cobalt-chelating prosthetic group of vitamin B12 and share numerous features with the iron-chelating porphyrin present in heme proteins/enzymes, constantly cross new boundaries ever since stable derivatives became easily accessible. Particularly important is the increasing utilization of corroles and the corresponding metal complexes for the benefit of mankind, in terms of new drug candidates for treating various diseases and as catalysts for sustainable energy relevant processes. One challenge is to gain access to the plain macrocycle, as to allow for full elucidation of the most fundamental properties of corroles. We have obtained the substituent-free corrole by several surprising and conceptually different pathways. Selected features of the corresponding metal complexes are illuminated, for pointing towards unique phenomena that are anticipated to largely expand the horizon regarding their utilization for contemporary catalysis.

Corroles: The Hitherto Elusive Parent Macrocycle and its Metal Complexes

AbstractCorroles, macrocycles that owe their name to the cobalt‐chelating prosthetic group of vitamin B12 and share numerous features with the iron‐chelating porphyrin present in heme proteins/enzymes, constantly cross new boundaries ever since stable derivatives became easily accessible. Particularly important is the increasing utilization of corroles and the corresponding metal complexes for the benefit of mankind, in terms of new drug candidates for treating various diseases and as catalysts for sustainable energy relevant processes. One challenge is to gain access to the plain macrocycle, as to allow for full elucidation of the most fundamental properties of corroles. We have obtained the substituent‐free corrole by several surprising and conceptually different pathways. Selected features of the corresponding metal complexes are illuminated, for pointing towards unique phenomena that are anticipated to largely expand the horizon regarding their utilization for contemporary catalysis.

Production of New Isoflavone Diglucosides from Glycosylation of 8-Hydroxydaidzein by Deinococcus geothermalis Amylosucrase

8-Hydroxydaidzein (8-OHDe) is a non-natural isoflavone polyphenol isolated from fermented soybean foods. 8-OHDe exhibits a wide range of pharmaceutical activities. However, both the poor solubility and instability of 8-OHDe limit its applications. To resolve the limitations of 8-OHDe, Deinococcus geothermalis amylosucrase (DgAS) has previously been used to glycosylate 8-OHDe to produce soluble and stable 8-OHDe-7-O-α-glucopyranoside (8-OHDe-7-G) in a 0.5 h reaction time. In this study, we aimed to use DgAS and an extended reaction time to produce 8-OHDe diglucosides. At least three 8-OHDe derivatives were produced after a 24 h reaction time, and two major products were successfully purified and identified as new compounds: 8-OHDe-7-O-[α-glucopyranosyl-(1→6)-α-glucopyranoside] (8-OHDe-7-G2) and 8-OHDe-7,4′-O-α-diglucopyranoside (8-OHDe-7-G-4′-G). 8-OHDe-7-G-4′-G showed a 4619-fold greater aqueous solubility than 8-OHDe. In addition, over 92% of the 8-OHDe diglucosides were stable after 96 h, while only 10% of the 8-OHDe could be detected after being subjected to the same conditions. The two stable 8-OHDe diglucoside derivatives have the potential for pharmacological usage in the future.

Simple and Reproducible Derivatization with Benzoyl Chloride: Improvement of Sensitivity for Multiple Lipid Classes in RP-UHPLC/MS.

The chemical derivatization of multiple lipid classes was developed using benzoyl chloride as a nonhazardous derivatization agent at ambient conditions. The derivatization procedure was optimized with standards for 4 nonpolar and 8 polar lipid classes and measured by reversed-phase ultrahigh-performance liquid chromatography-tandem mass spectrometry. The derivatization and nonderivatization approaches were compared on the basis of the calibration curves of 22 internal standards from 12 lipid classes. The new method decreased the limit of detection 9-fold for monoacylglycerols (0.9-1.0 nmol/mL), 6.5-fold for sphingoid base (0.2 nmol/mL), and 3-fold for diacylglycerols (0.9 nmol/mL). The sensitivity expressed by the ratio of calibration slopes was increased 2- to 10-fold for almost all investigated lipid classes and even more than 100-fold for monoacylglycerols. Moreover, the benzoylation reaction produces a more stable derivative of cholesterol in comparison to the easily in-source fragmented nonderivatized form and enabled the detection of fatty acids in a positive ion mode, which does not require polarity switching as for the nonderivatized form. The intralaboratory comparison with an additional operator without previous derivatization experiences shows the simplicity, robustness, and reproducibility. The stability of the derivatives was determined by periodical measurements during a one month period and five freeze/thaw cycles. The fully optimized derivatization method was applied to human plasma, which allows the detection of 169 lipid species from 11 lipid classes using the high confidence level of identification in reversed-phase (RP)-ultra high performance liquid chromatography (UHPLC)/mass spectrometry (MS). Generally, we detected more lipid species for monoacylglycerols, diacylglycerols, and sphingoid bases in comparison with previously reported papers without the derivatization.

Probing the Ca2+ mobilizing properties on primary cortical neurons of a new stable cADPR mimic

Cyclic adenosine diphosphate ribose (cADPR) is a second messenger involved in the Ca2+ homeostasis. Its chemical instability prompted researchers to tune point by point its structure, obtaining stable analogues featuring interesting biological properties. One of the most challenging derivatives is the cyclic inosine diphosphate ribose (cIDPR), in which the hypoxanthine isosterically replaces the adenine. As our research focuses on the synthesis of N1 substituted inosines, in the last few years we have produced new flexible cIDPR analogues, where the northern ribose has been replaced by alkyl chains. Interestingly, some of them mobilized Ca2+ ions in PC12 cells. To extend our SAR studies, herein we report on the synthesis of a new stable cIDPR derivative which contains the 2″S,3″R dihydroxypentyl chain instead of the northern ribose. Interestingly, the new cyclic derivative and its open precursor induced an increase in intracellular calcium concentration ([Ca2+]i) with the same efficacy of the endogenous cADPR in rat primary cortical neurons.