Modulating the phototoxicity and selectivity of a porphyrazine towards epidermal tumor cells by coordination with metal ions.

Porphyrazines (Pzs) are porphyrin derivatives that show potential application as photosensitizers for photodynamic therapy (PDT), but are still far less explored in the literature. In this work, we evaluate how the photophysics and phototoxicity of the octakis(trifluoromethylphenyl)porphyrazine (H2Pz) against tumor cells can be modulated by coordination with Mg(II), Zn(II), Cu(II) and Co(II) ions. Fluorescence and singlet oxygen quantum yields for the Pzs were measured in organic solvents and in soy phosphatidylcholine (PC) liposomes suspended in water. While H2Pz and the respective complexes with Cu(II) and Co(II) showed very low efficiency to fluoresce and to produce 1O2, the Mg(II) and Zn(II) complexes showed significantly higher quantum yields in organic solvents. The fluorescence of these two Pzs in the liposomes was sensitive to the fluidity of the membrane, showing potential use as viscosity markers. The cytotoxicity of the compounds was tested in HaCaT (normal) and A431 (tumor) cells using soy PC liposomes as drug carriers. Despite the low 1O2 quantum yields in water, the Mg(II) and Zn(II) complexes showed IC50 values against A431 cells in the nanomolar range when activated with low doses of red LED light. Their phototoxicity was ca. three times higher for the tumor cells compared to the normal ones, showing promising application as photosensitizers for PDT protocols. Considering that H2Pz and the respective Co(II) and Cu(II) complexes were practically non-phototoxic to the cells, we demonstrate the importance of the central metal ion in the modulation of the photodynamic activity of porphyrazines.

Photoluminescence and magnetic properties of isostructural europium(III), gadolinium(III) and terbium(III) oxamate-based coordination polymers.

Developing and investigating advanced multifunctional materials with magnetic properties as candidates for assembling spin qubits for quantum computing is imperative. A new polytopic ligand based on oxamate and aniline was used to promote the synthesis of three neutral homometallic lanthanide-coordinated polymers. New complexes with the formula {Ln(phox)3(DMSO)2(H2O)}n, where Ln = Eu3+ (1), Gd3+ (2), and Tb3+ (3) [phox = N-(phenyl)oxamate and DMSO = dimethylsulfoxide], were synthesized and well characterized by spectroscopic methods as well as X-ray crystallographic analysis. All crystalline structures comprise neutral zigzag chains. The lanthanide ions are linked by three phox ligands, in which two oxygen atoms from two different ligands are responsible for connecting the trivalent lanthanide ions, and one phox ligand completes the coordination sphere in a bis-bidentate mode, together with two DMSO molecules and one water coordination molecule. The coordination sphere of lanthanide ions consisted of spherical capped square antiprism (CSAPR-9) symmetry. The magnetic properties of 1-3 were investigated in the 2-300 K temperature range. The dynamic (ac) magnetic properties of 2 reveal a frequency dependence involving the phonon bottleneck mechanism below 33 K under nonzero applied dc magnetic fields, resulting in an example of a field-induced single-molecule magnet. Solid-state photophysical measurements for Eu3+ (1) and Tb3+ (3) complexes indicate that the N-(phenyl)oxamate ligands are very efficient in sensitizing the lanthanide(III) ions in the visible region of the electromagnetic spectrum. Compounds 1 and 3 exhibited an emission in the red and green regions, respectively. Experimental results and theoretical calculations using the Sparkle/RM1 method support a quantum efficiency of ∼72% for 1, suggesting its potential as a candidate for light conversion molecular devices (LCMDs).

Multivariate Analysis of Solubility Parameters for Drug-Polymer Miscibility Assessment in Preparing Raloxifene Hydrochloride Amorphous Solid Dispersions.

The success of obtaining solid dispersions for solubility improvement invariably depends on the miscibility of the drug and polymeric carriers. This study aimed to categorize and select polymeric carriers via the classical group contribution method using the multivariate analysis of the calculated solubility parameter of RX-HCl. The total, partial, and derivate parameters for RX-HCl were calculated. The data were compared with the results of excipients (N = 36), and a hierarchical clustering analysis was further performed. Solid dispersions of selected polymers in different drug loads were produced using solvent casting and characterized via X-ray diffraction, infrared spectroscopy and scanning electron microscopy. RX-HCl presented a Hansen solubility parameter (HSP) of 23.52 MPa1/2. The exploratory analysis of HSP and relative energy difference (RED) elicited a classification for miscible (n = 11), partially miscible (n = 15), and immiscible (n = 10) combinations. The experimental validation followed by a principal component regression exhibited a significant correlation between the crystallinity reduction and calculated parameters, whereas the spectroscopic evaluation highlighted the hydrogen-bonding contribution towards amorphization. The systematic approach presented a high discrimination ability, contributing to optimal excipient selection for the obtention of solid solutions of RX-HCl.

Electrochemical Diselenation of BODIPY Fluorophores for Bioimaging Applications and Sensitization of 1 O2.

Invited for the cover of this issue are the groups of Holger Braunschweig at the Julius-Maximilians-Universität Würzburg, Germany and Eufrânio N. da Silva Júnior at the Universidade Federal de Minas Gerais, UFMG, Brazil. The image depicts the electrochemical synthesis of selenium-containing BODIPY molecules with lightning symbolizing the electrifying synthetic process, while the surrounding elemental chaos hints at the red-shifted absorption and emission and the transformative photophysical properties of these new compounds. Read the full text of the article at 10.1002/chem.202303883.

Intensity and lifetime ratiometric luminescent thermometer based on a Tb(III) coordination polymer.

A three-dimensional terbium(III) coordination polymer of formula [Tb(bttb)0.5(2,5-pzdc)0.5]n (1) [H4bttb = 1,2,4,5-tetrakis(4'-carboxyphenyl)benzene and H2-2,5-pzdc = 2,5-pyrazinedicarboxylic acid] was obtained under hydrothermal conditions. The bttb4- tetraanion in 1 adopts the bridging and chelating-bridging pseudo-oxo coordination modes while the 2,5-pzdc2- dianion exhibits a rather unusual bis-bidentate bridging pseudo-oxo coordination mode, both ligands being responsible for the stiffness of the resulting 3D structure. Solid-state photoluminescent measurements illustrate that 1 exhibits remarkable green luminescence emission, the most intense band occurring in the region of 550 nm (5D4 → 7F5) with lifetimes at the millisecond scale. Thermometric performances of 1 reveal a maximum relative sensitivity (Sm) of 0.76% K-1 at 295 K (δT = 0.05 K), constituting a TbIII ratiometric solid luminescent thermometer over the physiological temperature range. Variable-temperature static (dc) magnetic susceptibility measurements for 1 in the temperature range 2.0-300 K show the expected behavior for the depopulation of the splitted mJ levels of the 7F7 ground state of the magnetically anisotropic terbium(III) ion plus a weak antiferromagnetic interaction through the carboxylate bridges. No significant out-of-phase magnetic susceptibility signals were observed for 1 in the temperature range 2.0-10.0 K, either in the absence or presence of a static dc magnetic field.

Electrochemical Diselenation of BODIPY Fluorophores for Bioimaging Applications and Sensitization of 1 O2.

We report a rapid, efficient, and scope-extensive approach for the late-stage electrochemical diselenation of BODIPYs. Photophysical analyses reveal red-shifted absorption - corroborated by TD-DFT and DLPNO-STEOM-CCSD computations - and color-tunable emission with large Stokes shifts in the selenium-containing derivatives compared to their precursors. In addition, due to the presence of the heavy Se atoms, competitive ISC generates triplet states which sensitize 1 O2 and display phosphorescence in PMMA films at RT and in a frozen glass matrix at 77 K. Importantly, the selenium-containing BODIPYs demonstrate the ability to selectively stain lipid droplets, exhibiting distinct fluorescence in both green and red channels. This work highlights the potential of electrochemistry as an efficient method for synthesizing unique emission-tunable fluorophores with broad-ranging applications in bioimaging and related fields.

Study of the Counter Cation Effects on the Supramolecular Structure and Electronic Properties of a Dianionic Oxamate-Based {NiII2} Helicate.

Herein, we describe the synthesis, crystal structure, and electronic properties of {[K2(dmso)(H2O)5][Ni2(H2mpba)3]·dmso·2H2O}n (1) and [Ni(H2O)6][Ni2(H2mpba)3]·3CH3OH·4H2O (2) [dmso = dimethyl sulfoxide; CH3OH = methanol; and H4mpba = 1,3-phenylenebis(oxamic acid)] bearing the [Ni2(H2mpba)3]2- helicate, hereafter referred to as {NiII2}. SHAPE software calculations indicate that the coordination geometry of all the NiII atoms in 1 and 2 is a distorted octahedron (Oh) whereas the coordination environments for K1 and K2 atoms in 1 are Snub disphenoid J84 (D2d) and distorted octahedron (Oh), respectively. The {NiII2} helicate in 1 is connected by K+ counter cations yielding a 2D coordination network with sql topology. In contrast to 1, the electroneutrality of the triple-stranded [Ni2(H2mpba)3] 2- dinuclear motif in 2 is achieved by a [Ni(H2O)6]2+ complex cation, where the three neighboring {NiII2} units interact in a supramolecular fashion through four R22(10) homosynthons yielding a 2D array. Voltammetric measurements reveal that both compounds are redox active (with the NiII/NiI pair being mediated by OH- ions) but with differences in formal potentials that reflect changes in the energy levels of molecular orbitals. The NiII ions from the helicate and the counter-ion (complex cation) in 2 can be reversibly reduced, resulting in the highest faradaic current intensities. The redox reactions in 1 also occur in an alkaline medium but at higher formal potentials. The connection of the helicate with the K+ counter cation has an impact on the energy levels of the molecular orbitals; this experimental behavior was further supported by X-ray absorption near-edge spectroscopy (XANES) experiments and computational calculations.

It Takes Two to Tango, Part II: Synthesis of A-Ring Functionalised Quinones Containing Two Redox-Active Centres with Antitumour Activities.

In 2021, our research group published the prominent anticancer activity achieved through the successful combination of two redox centres (ortho-quinone/para-quinone or quinone/selenium-containing triazole) through a copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. The combination of two naphthoquinoidal substrates towards a synergetic product was indicated, but not fully explored. Herein, we report the synthesis of 15 new quinone-based derivatives prepared from click chemistry reactions and their subsequent evaluation against nine cancer cell lines and the murine fibroblast line L929. Our strategy was based on the modification of the A-ring of para-naphthoquinones and subsequent conjugation with different ortho-quinoidal moieties. As anticipated, our study identified several compounds with IC50 values below 0.5 µM in tumour cell lines. Some of the compounds described here also exhibited an excellent selectivity index and low cytotoxicity on L929, the control cell line. The antitumour evaluation of the compounds separately and in their conjugated form proved that the activity is strongly enhanced in the derivatives containing two redox centres. Thus, our study confirms the efficiency of using A-ring functionalized para-quinones coupled with ortho-quinones to obtain a diverse range of two redox centre compounds with potential applications against cancer cell lines. Here as well, it literally takes two for an efficient tango!

3-phenacylideneoxindoles as a new class of antifungal compounds against Paracoccidioides spp.

Aims: Considering the need to identify new compounds with antifungal action, the activity of five 3-phenacylideneoxindoles compounds was evaluated. Materials & methods: The compounds were synthesized, and their antifungal activity was elucidated through minimum inhibitory concentration tests and interaction assay with other antifungals. Potential targets of compounds were predicted in silico. Results: 3-phenacylideneoxindoles compounds inhibited fungal growth with minimum inhibitory concentration and minimum fungicidal concentration ranging from 3.05 to 12.26 µM. The compounds demonstrated high selectivity index and presented a synergistic effect with itraconazole. In silico prediction revealed the pentafunctional AROM polypeptide, enolase, superoxide dismutase, catalase and kinases as proteins targets of the compound 4a. Conclusion: The results demonstrate that 3-phenacylideneoxindoles is a potential new class of antifungal compounds for paracoccidioidomycosis treatment.

Patients affected by paracoccidioidomycosis (PCM) require long-term treatment, which commonly influences their adherence. In addition, only three drugs are in clinical use, which indicates the relevance of research in identifying new drugs for treating PCM. Thus, five drugs were tested in the laboratory to verify whether they could prevent the growth of the fungus without being toxic to humans. In addition, whether these compounds in combination with drugs used to treat PCM could be even more potent was evaluated. All compounds tested efficiently inhibited the growth of Paracoccidioides, the fungus that causes PCM. One drug was identified that, combined with itraconazole, decreased the required dose of both the discovered compound and itraconazole needed to inhibit fungal growth. Using computational tools, this work suggests how the new drug could act against the fungus. The results demonstrate a potential new treatment option, but more studies are needed to confirm the safety of these drugs.

Trinuclear Cobalt(II) Triple Helicate with a Multidentate Bithiazolebis(oxamate) Ligand as a Supramolecular Nanomagnet.

The cobalt(II)-mediated self-assembly of the potentially tris(chelating) N,N'-2,2'-(4,4'-bithiazole)bis(oxamate) (dabtzox) ligand gives a new metal-organic supramolecular nanomagnet of formula K6Co3(dabtzox)3·8H2O·MeOH (1) featuring a unique linear triple-stranded trinuclear structure of the helicate type.

2,5-Diketopiperazines via Intramolecular N-Alkylation of Ugi Adducts: A Contribution to the Synthesis, Density Functional Theory Study, X-ray Characterization, and Potential Herbicide Application.

To investigate the herbicidal potential of 2,5-diketopiperazines (2,5-DKPs), we applied a known protocol to produce a series of 2,5-DKPs through intramolecular N-alkylation of Ugi adducts. However, the method was not successful for the cyclization of adducts presenting aromatic rings with some substituents at the ortho position. Results from DFT calculations showed that the presence of voluminous groups at the ortho position of a benzene ring results in destabilization of the transition structure. Lower activation enthalpies for the SN2-type cyclization of Ugi adducts were obtained when bromine, instead of a chlorine anion, is the leaving group, indicating that the activation enthalpy for the cyclization step controls the formation of the 2,5-DKP. Some Ugi adducts and 2,5-DKPs formed crystals with suitable qualities for single-crystal X-ray diffraction data collection. Phytotoxic damage of some 2,5-DKPs on leaves of the weed Euphorbia heterophylla did not differ from those caused by the commercial herbicide diquat.

Building-up host-guest helicate motifs and chains: a magneto-structural study of new field-induced cobalt-based single-ion magnets.

In this work, we present the synthetic pathway, a refined structural description, complete solid-state characterization and the magnetic properties of four new cobalt(ii) compounds of formulas [Co(H2O)6][Co2(H2mpba)3]·2H2O·0.5dmso (1), [Co(H2O)6][Co2(H2mpba)3]·3H2O·0.5dpss (2), [Co2(H2mpba)2(H2O)4]n·4nH2O (3), and [Co2(H2mpba)2(CH3OH)2(H2O)2]n·0.5nH2O·2ndpss (4) [dpss = 2,2'-dipyridyldisulfide and H4mpba = 1,3-phenylenebis(oxamic) acid], where 2 and 4 were obtained from [Co(dpss)Cl2] (Pre-I) as the source of cobalt(ii). All four compounds are air-stable and were prepared under ambient conditions. 1 and 2 were obtained from a slow diffusion method [cobalt(ii) : H2mpba2- molar ratio used 1 : 1] and their structures are made up of [Co2(H2mpba)3]2- anionic helicate units and [Co(H2O)6]2+ cations, exhibiting supramolecular three-dimensional structures. Interestingly, a supramolecular honeycomb network between the helicate units interacting with each other through R22(10) type hydrogen bonds occurs in 2 hosting one co-crystallized dpss molecule. On the other hand, for the first time, linear (3) and zigzag (4) cobalt(ii) chains were isolated by slow evaporation of stirred solutions of mixed solvents with cobalt(ii) : H2mpba2- in 1 : 2 molar ratio at room temperature. Magnetic measurements of Pre-I revealed a quasi magnetically isolated S = 3/2 spin state with a significant second-order spin-orbit contribution as expected for tetrahedrally coordinated cobalt(ii) ions. The analysis of the variable temperature static (dc) magnetic susceptibility data through first- (1 and 3) and second-order spin-orbit coupling models (2 and 4) reveals the presence of magnetically non-interacting high-spin cobalt(ii) ions with easy-axis (1 and 4)/easy-plane magnetic anisotropies (2 and 4) with low rhombic distortions. Dynamic (ac) magnetic measurements for Pre-I and 1-4 below 8.0 K show that they are examples of field-induced Single-Ion Magnets (SIMs).

Metal-Cocatalyst Interaction Governs the Catalytic Activity of MII-Porphyrazines for Chemical Fixation of CO2.

Chemical fixation of CO2 to produce cyclic carbonates can be a green and atomic efficient process. In this work, a series of porphyrazines (Pzs) containing electron-withdrawing groups and central MII ions (where M = Mg, Zn, Cu, and Co) were synthesized and investigated as catalysts for the cycloaddition of CO2 to epoxides. Then, the efficiency of the Pzs was tested by varying cocatalyst type and concentration, epoxide, temperature, and pressure. MgIIPz bearing trifluoromethyl groups (1) showed the best conversion, producing, selectively, 78% of propylene cyclic carbonate (PCC), indicating that a harder and stronger Lewis acid is more effective for epoxide activation. Moreover, cocatalyst variation showed a notable effect on the reaction yields. Spectrophotometric titrations, MALDI-TOF mass spectra, and theoretical calculations suggest poisoning of the catalyst when tetrabutylammonium chloride (TBAC) and large amounts of tetrabutylammonium bromide (TBAB) were used in the system. The same was not observed for tetrabutylammonium iodide (TBAI), indicating that the metal-cocatalyst interaction may govern the reaction rate. In addition, two rare examples of crystalline structures were obtained, proving the distorted square pyramidal geometry with water molecule as axial ligand. This is one of the first studies reporting Pzs as catalysts for the chemical fixation of CO2, and we believe that the intricate balance between cocatalyst concentration and conversion efficiency shown here may aid future studies in the area.

Mononuclear lanthanide(III)-oxamate complexes as new photoluminescent field-induced single-molecule magnets: solid-state photophysical and magnetic properties.

Implementing additional optical (luminescent) properties into the well-known class of single-molecule magnets (SMMs) is considered as a promising route toward obtaining the next generation of optomagnetic materials for quantum information storage and computing. Herein, we report a joint optical and magneto-structural study for the two novel series of lanthanide(iii) complexes of general formula Bu4N[LnIII(HL)4(dmso)]·nH2O where H2L = N-(4-Xphenyl)oxamic acid with X = Cl and n = 2 [Ln = Eu (1_Cl), Gd (2_Cl), Dy (3_Cl), and Tb (4_Cl)] and X = F and n = 3 [Ln = Eu (1_F), Gd (2_F), Dy (3_F), and Tb (4_F)]. All these compounds are mononuclear species with each lanthanide(iii) cation in a low-symmetry nine-coordinate environment (LnO9) which is constituted by four didentate monoprotonated oxamate groups and one dmso molecule. Magnetic measurements show the occurrence of field-induced SMM behavior for the Gd3+ (2_Cl and 2_F), Dy3+ (3_Cl and 3_F), and Tb3+ complexes (4_Cl and 4_F). Solid-state photophysical measurements for the Eu3+ (1_Cl and 1_F) and Tb3+ complexes (4_Cl and 4_F) reveal that both monoprotonated chloro- and fluoro-substituted phenyl(oxamate) ligands are able to sensitize the lanthanide(iii)-based luminescence in the visible region, through an energy transfer process ("antenna effect"), as supported by theoretical calculations for Eu3+ compounds. In particular, 1_Cl and 1_F present a quantum efficiency of approximately 50%, being potentially suitable as efficient light conversion molecular devices (LCMDs).

Synthesis, anti-proliferative activity, theoretical and 1H NMR experimental studies of Morita-Baylis-Hillman adducts from isatin derivatives.

Quaternary or spirocyclic 3-substituted-3-hydroxy-2-oxindole is considered a privileged scaffold. In other words, it is a molecular core present on several compounds with a wide spectrum of biological activities. Among its precursors, activated ketones (isatin nucleus) can be used as interesting starting points to Morita-Baylis-Hillman adducts derivatives, a class of compounds with good cytotoxic potential. In this paper, we present the synthesis, anti-proliferative activity against lung cancer cell line and a theoretical conformational study of 21 of Morita-Baylis-Hillman adducts from isatin derivatives, by DFT quantum chemical calculations, followed by a SAR and QSAR analysis. Besides, an efficient synthetic protocol and good biological activity profile were highlighted interesting observations about 1H NMR experimental spectra, molecular modeling results and crystallographic data available.

Carbamoyl-N-aryl-imine-urea: a new framework to obtain a putative leishmanicidal drug-candidate.

Leishmaniasis is a neglected parasitic disease, and current treatment includes limitations of toxicity, variable efficacy, high costs and inconvenient doses and treatment schedules. Therefore, new leishmanicidal drugs are still an unquestionable medical need. In this paper we described the design conception of a new framework, the carbamoyl-N-aryl-imine-urea, to obtain putative leishmanicidal drug-candidates. Compounds 9a-e and 10a-e were designed and synthesized and their leishmanicidal activity was studied in comparison to pentamidine, miltefosine and meglumine antimoniate. The conformational profile of the new carbamoyl-N-aryl-imine-urea framework was investigated by X-ray diffraction studies, using compound 9a as a model. The plasma stability of this putative peptide mimetic subunit was studied for compound 10e (LASSBio-1736). Among the congeneric series, LASSBio-1736 was identified as a new antileishmanial drug-candidate, displaying plasma stability, cytotoxicity against amastigote forms of L. amazonensis and L. braziliensis, and leishmanicidal activity in a cutaneous leishmaniasis murine model, without preliminary evidence of hepatic or renal toxicity.

Exploring the structural landscape of 2-(thiophen-2-yl)-1,3-benzothiazole: high-Z' packing polymorphism and cocrystallization with calix[4]tube.

We report here for the first time a cocrystal of the so-called neutral calix[4]tube, which is two tail-to-tail-arranged and partially deprotonated tetrakis(carboxymethoxy)calix[4]arenes, including three sodium ions, with 2-(thiophen-2-yl)-1,3-benzothiazole, namely trisodium bis(carboxymethoxy)bis(carboxylatomethoxy)calix[4]arene tris(carboxymethoxy)(carboxylatomethoxy)calix[4]arene-2-(thiophen-2-yl)-1,3-benzothiazole-dimethyl sulfoxide-water (1/1/2/2), 3Na+·C36H30O122-·C36H31O12-·C11H7NS2·2C2H6OS·2H2O, which provides a new approach into the host-guest chemistry of inclusion complexes. Three packing polymorphs of the same benzothiazole with high Z' (one with Z' = 8 and two with Z' = 4) were also discovered in the course of our desired cocrystallization. The inspection of these polymorphs and a previously known polymorph with Z' = 2 revealed that Z' increases as the strength of intermolecular contacts decreases. Also, these results expand the frontier of invoking calixarenes as a host for nonsolvent small molecules, besides providing knowledge on the rare formation of high-Z' packing polymorphs of simple molecules, such as the target benzothiazole.

ss-NMR and single-crystal X-ray diffraction in the elucidation of a new polymorph of bischalcone (1E,4E)-1,5-bis(4-fluorophenyl)penta-1,4-dien-3-one.

We report a new polymorph of (1E,4E)-1,5-bis(4-fluorophenyl)penta-1,4-dien-3-one, C17H12F2O. Contrary to the precedent literature polymorph with Z' = 3, our polymorph has one half molecule in the asymmetric unit disordered over two 50% occupancy sites. Each site corresponds to one conformation around the single bond vicinal to the carbonyl group (so-called anti or syn). The other half of the bischalcone is generated by twofold rotation symmetry, giving rise to two half-occupied and overlapping molecules presenting both anti and syn conformations in their open chain. Such a disorder allows for distinct patterns of intermolecular C-H...O contacts involving the carbonyl and anti-oriented ß-C-H groups, which is reflected in three 13C NMR chemical shifts for the carbonyl C atom. Here, we have also assessed the cytotoxicity of three symmetric bischalcones through their in vitro antitumour potential against three cancer cell lines. Cytotoxicity assays revealed that this biological property increases as halogen electronegativity increases.

2D and 3D mixed MII/CuII metal-organic frameworks (M = Ca and Sr) with N,N'-2,6-pyridinebis(oxamate) and oxalate: preparation and magneto-structural study.

Three heterobimetallic complexes of formula [Ca2Cu3(mpyba)2(2-apyma)(H2O)7]·8.3H2O (1), [Sr2Cu3(mpyba)2(2-apyma)(H2O)8]·11.6H2O (2) and [Sr4.5Cu4(mpyba)4(ox)(H2O)20]·8.5H2O (3) [H4mpyba = N,N'-2,6-pyridinebis(oxamic acid), 2-apyma = 2-(6-aminopyridinyl)oxamate and ox = oxalate] have been synthesized and structurally characterized. Complexes 1 and 2 are isostructural compounds, with tricopper(ii) units having mpyba and its hydrolytic product (2-apyma) as ligands. They are interlinked through strontium(ii) (1) and calcium(ii) (2) ions to afford neutral two-dimensional networks. Two of the copper(ii) ions are five-coordinate in distorted square pyramidal (Cu3) and trigonal bipyramidal (Cu1) surroundings, whereas the other (Cu2) is six-coordinate in an elongated octahedral environment. The main difference between their structures, apart from the number of water molecules, resides in the nature of the alkaline earth cation coordinated to the oxamate fragments, Sr2+ (1)/Ca2+ (2), which exhibit eight and seven coordination, respectively. The π-π interactions and an extensive network of hydrogen bonds in 1 and 2 lead to supramolecular 3D structures. The relatively small size of their cavities, in the micropore domain, hinders the inclusion of N2 but allows CO2 adsorption (0.45 and 0.52 mmol g-1 for 1 and 2, respectively). The structure of 3 is made up of [3,3] metallacyclophane-type motifs, having the formula [Cu2(mpyba)2(H2O)2]4-. These act as tetrakis(bidentate) ligands towards the strontium(ii) ions (Sr1, Sr2 and Sr3), leading to a sheet-like polymer growing in the bc plane, which extends further along the crystallographic a axis by a bis(chelating) oxalate between the Sr1 atoms. The investigation of the magnetic properties of 1-3 in the temperature range 1.9-300 K shows the occurrence of an overall antiferromagnetic behaviour for 1 and 2 [J12 = J23 = -9.71(2) (1) and -10.81(5) cm-1 (2), with the Hamiltonian being defined as H = -J12S1·S2 - J23S2·S3 + gßH[S1 + S2 + S3], and a ferromagnetic coupling within the dicopper(ii) metallacylophane unit of 3 [J = +1.86(1) cm-1 through the Hamiltonian H = -JS1·S2 + gßH(S1 + S2)]. Simple orbital symmetry considerations (1-3) and the spin polarization mechanism (3) account for the observed magnetic properties.

Semisynthesis and absolute configuration of a novel rearranged 19,20-δ-lactone (9ßH)-pimarane diterpene.

Annonalide (3ß,20-epoxy-3α,16-dihydroxy-15-oxo-7-pimaren-19,6ß-olide, C20H26O6, 1) is the major (9ßH)-pimarane diterpene isolated from tubers of Cassimirella ampla, and it exhibits cytotoxic properties upon interaction with ctDNA. We have prepared new derivatives of 1 by modification of the (9ßH)-pimarane backbone and report here the semisynthesis and absolute configuration of a novel rearranged 19,20-δ-lactone (9ßH)-pimarane. Our approach was the reduction of the carbonyl groups of 1 with sodium borohydride, at positions C15 (no stereoselectivity) and C3 (stereoselective reduction), followed by rearrangement of the 6,19-γ-lactone ring into the six-membered 19,20-δ-lactone ring in 4a (3ß,6ß,16-trihydroxy-7-pimaren-19,20ß-olide monohydrate, C20H30O6·H2O). The absolute structure of the new compound, 4a, was determined unambiguously with a Flack parameter x of -0.01 (11), supporting the stereochemistry assignment of 1 redetermined here. Besides the changes in the pattern of covalent bonds caused by reduction and lactone rearrangement, the conformation of one of the three fused cyclohexane rings is profoundly different in 4a, adopting a chair conformation instead of the boat shape found in 1. Furthermore, the intramolecular hydrogen bond present in 1 is lost in new compound 4a, due to hydrogen bonding between the 3-OH group and the solvent water molecule.