Iminopyrrole-Based Self-Assembly: A Route to Intrinsically Flexible Molecular Links and Knots.

The use of 2,5-diformylpyrrole in self-assembly reactions with diamines and Zn(II)/Cd(II) salts allowed the preparation of [2]catenane, trefoil knot, and Borromean rings. The intrinsically dynamic nature of the diiminopyrrole motif rendered all of the formed assemblies intramolecularly flexible. The presence of diiminopyrrole revealed new coordination motifs and influenced the host-guest chemistry of the systems, as illustrated by hexafluorophosphate encapsulation by Borromean rings.

21-Carba-23-selenaporphyrinoid Dyads-An Azepine Unit as a Merging Motif.

The oxidation of 10,15-diaryl-21-carba-23-selenaporphyrinoids resulted in the creation of dyads. The dimerization process follows a [5+2] cycloaddition path with the formation of an azepine unit. The arrays display two direct bonds between the peripheral carbocyclic carbon atoms of one carbaselenaporphyrinic subunit and the central carbon and nitrogen atoms of the second subunit. This results in a unique canted arrangement of two carbaporphyrinoid planes resembling an open seashell-like motif.

Bromine versus chlorine substituent in breathing crystals of a copper(I) coordination compound with a triazolamine Schiff base.

It is known that N-[4-(chlorobenzylidene)-4H-1,2,4-triazol-4-amine in reaction with copper(I) perchlorate(VII) forms metastable breathing crystals built up of X-shaped binuclear units containing copper(I) ions in a trigonal coordination sphere. Using trifluoromethanesulfonate instead of perchlorate(VII) affects the self-assembly of the X-shaped units and the breathing function of the resulting crystals. The latter are not breathing crystals. Copper(I) trifluoromethanesulfonate with N-[4-(bromobenzylidene)-4H-1,2,4-triazol-4-amine crystallizes in two forms: open (with the presence of 1D channels) and closed (without 1D channels). Both are characterized by the presence of X-shaped binuclear cationic units and the trigonal coordination sphere of copper(I) ions. The open form has the ability to engage in reversible sorption. The desorption process is associated with the large reorientation of the binuclear units and the reorganization of the intermolecular interactions leading to the closure of the channels. The post-synthetically obtained channel-less form differs from the channel-less form obtained by direct crystallization, the latter being incapable of sorption. The mechanism of the desorption process of the open form is governed by the general principle of dense packing, and the main reason for the sorption process is the formation of directional halogen-halogen interactions. The halogen atom in the para position of the ligands influences the formation of different crystalline forms and also a different mechanism for the desorption process.

The Intracavity Extension of 28-Hetero-2,7-naphthiporphyrins in Reactions with Alkylamines.

The 28-hetero-2,7-naphthiporphyrins reacted with triethylamine and diethylamine to form nonaromatic intracavity-extended macrocycles incorporating naphthodihydro-2H-pyran, naphthotetrahydropyridine, and naphthopyrrolotetrahydro-1H-azepine moieties. The new macrocycles were characterized in solution by means of NMR and UV-vis spectroscopy and in the solid state by XRD.

POSSaxanes: active-template synthesis of organic-inorganic rotaxanes incorporating cubic silsesquioxane stoppers.

The CuAAC active-template approach was exploited to construct rotaxanes incorporating cage-like silsesquioxane stoppers, namely, POSSaxanes. The compounds were characterized in the solution and solid state, providing the unprecedented molecular structures of POSS-incorporating rotaxanes.

Chalcone-Derived Lactones: Synthesis, Whole-Cell Biotransformation, and Evaluation of Their Antibacterial and Antifungal Activity.

Four compounds with lactone moiety were synthesized from chalcone 1 in three- or four-step synthesis. γ-Bromo-δ-lactone 5 was the only product of bromolactonization of acid 4 whereas bromolactonization of ester 3, apart from lactone 5 also afforded its isomer 6 and two diastereoisomeric δ-hydroxy-γ-lactones 7 and 8. Lactone 8 was also obtained in 88% yield as a product of simultaneous dehalogenation and translactonization of γ-bromo-δ-lactone 5 by Penicillum frequentans AM 359. Chalcone-derived lactones 5-8 were subjected to the tests on antimicrobial activity and the results compared with activity of starting chalcone 1. Obtained lactones 5-8 in most cases limited the growth of tested bacterial and fungal strains. The highest activity was found for δ-hydroxy-γ-lactone 8 which completely inhibited the growth of Staphylococcus aureus, Fusarium graminearum, Aspergillus niger, and Alternaria sp. The introduction of lactone moiety into chalcone scaffold significantly improved antimicrobial activity of the compound: γ-bromo-δ-lactone 6 and δ-hydroxy-γ-lactone 8 were significantly stronger growth inhibitors of S. aureus and F. graminearum. In the case of the latter, a clear positive effect of the lactone function on the antifungal activity was also observed for γ-bromo-δ-lactone 5.

Heterobimetallic 21,23-dimetallaporphyrin: activation of metal-metal interactions within the porphyrinoid macrocycle.

Two core-modified porphyrins containing metal atoms, namely platinum(II) or platinum(IV) and rhodium(III), in place of two NH units, have been obtained by a post-synthetic modification of the 21,23-ditelluraporphyrin. The products of the tellurium-to-metal exchange, 21-platina-23-rhodaporphyrins, incorporate rhodacyclopentadiene and platinacyclopentadiene units with the metal atoms facing each other. The two molecules exhibit different degrees of metal-metal interaction depending on the oxidation state of platinum, with the NBO bond order being 0.04 for platinum(IV) and 0.15 for platinum(II). Consistently, the Quantum Theory of Atoms in Molecules analysis revealed the presence of the bond determinant, the bond critical point, in the platinum(II) species, in contrast to the platinum(IV) congener. The two porphyrinoids are interconvertible in redox reactions. They both exhibit fluxional behaviour in solution, studied by 1H NMR, involving alteration in the metal ion coordination sphere accompanied by the macrocyclic skeleton conformation change.

Progressive Structural Complexity in Ferroelectric 1,2,4-Triazolium Hexabromoantimonate(III): Interplay of "Order-Disorder" and "Displacive" Contributions to the Structural Phase Transitions.

Halobismuthates(III) and haloantimonates(III) with the R3MX6 chemical composition create a new and broadly unexplored class of ferroelectric compounds. In this paper, we report the haloantimonate(III) ferroelectric comprising an aromatic (1,2,4-triazolium) cation, i.e., (C2N3H4)3[SbBr6] (TBA). Temperature-resolved structural and spectroscopic studies indicate that TBA undergoes two solid-solid phase transitions between tetragonal [P42/m (I)] and monoclinic [P21/n (II) and P21 (III)] phases. TBA experiences a paraelectric-ferroelectric phase transition at 271/268 K (II-III) driven by "order-disorder" and "displacive" molecular mechanisms. The ferroelectric properties of phase III have been confirmed by hysteresis loop measurement, and additionally, the acentric order has been further supported by second-harmonic generation measurements. Insight into the molecular origins of the ferroelectric polarization was provided by periodic ab initio calculations using the Berry phase approach at the density functional theory (DFT-D3) method level employed for calculations of spontaneous polarization.

Plenates: Anion-Dependent Self-Assembly of the Pyrrole Cage Encapsulating Silver(I) Clusters.

The self-assembly of 2,5-diformylpyrrole, tris(2-aminoethyl)amine, and silver(I) yielded, depending on the size and basicity of the anion, new cascade complexes or plenates, that is, cryptates incorporating Agn n+ clusters. The nature of the product was counterion-dependent, and its formation was either driven by cascade anion binding or by argentophilic interactions stabilizing the cluster within the cavity. The reaction of plenates with tetrabutylammonium halides resulted in the protonation-coupled replacement of the Ag3 3+ with anion(s), yielding cascade cryptates.

Metalation of Tellurophene: Reactivity of 21,23-Ditelluraporphodimethene toward Palladium(II), Platinum(II), and Rhodium(I).

Ditelluraporphodimethene, a nonaromatic porphyrinoid containing two tellurophene rings, reacted with palladium(II), platinum(II), and rhodium(I) following two different paths. Palladium(II) formed bonds to two tellurium donors of the macrocycle, yielding a side-on coordination compound, with a square planar (Te2Cl2) metal ion environment. An alternative reaction path has been observed for ditelluraporphodimethene with platinum(II) or rhodium(I) in high boiling solvents. These conditions led to the profound transformation, that is, one tellurium atom to a metal atom exchange, resulting in the formation of organometallic species containing metallacyclopentadiene rings, that is, 21-platina-23-telluraporphodimethene and 21-rhoda-23-telluraporphodimethene. The substitution reaction proceeded selectively at the tellurophene ring within the conjugated part of the molecule, that is, the tellurophene ring bound to two sp2 meso-carbon atoms. In the case of platinum, the exchange was accompanied by one meso-aryl ring fusion with the formed platinacyclopentadiene ring, and the platinum(II) macrocycle underwent reversible oxidation with chlorine. The products are stable and represent first nonaromatic examples of metalloporphyrinoids, with a metallacyclopentadiene ring incorporated into a porphodimethene skeleton.

Crownphyrins: Metal-Mediated Transformations of the Porphyrin-Crown Ether Hybrids.

Crownphyrins are hybrid macrocycles combining structural features of porphyrin and crown ethers. The molecular architecture renders them an intriguing class of hosts capable of binding neutral, and ionic guests. The presence of dynamic covalent imine linkages connecting the dipyrrin segment with the ether chain enables unusual coordination behavior of crownphyrins, as demonstrated by the formation of two classes of strikingly different complexes. The remarkable metal-mediated expansion to the helical [2+2] macrocyclic complex is reversible. The reaction of the figure-eight mercury(II) assembly with [2.2.2]cryptand results in ring contraction providing the metal-free crownphyrin macrocycle.

Two Rhodium(III) Ions Confined in a [18]Porphyrin Frame: 5,10,15,20-Tetraaryl-21,23-dirhodaporphyrin.

Invited for the cover of this issue is the group of Ewa Pacholska-Dudziak at the University of Wroclaw. The image depicts two rhodium atoms being fixed into the skeleton of 21,23-dirhodaporphyrin in place of two core nitrogen donors. Read the full text of the article at 10.1002/chem.202201513.

Two Rhodium(III) Ions Confined in a [18]Porphyrin Frame: 5,10,15,20-Tetraaryl-21,23-Dirhodaporphyrin.

Tetraaryl-21,23-dirhodaporphyrin and a series of related monorhodaporphyrins have been obtained by tellurium-to-rhodium exchange in a reaction of tetraaryl-21,23-ditelluraporphyrin with [RhCl(CO)2 ]2 . These organometallic metallaporphyrins contain rhodium(III) centers embedded in rhodacyclopentadiene rings, incorporated within the porphyrin frames. The skeletons of 21,23-dirhodaporphyrin and 21-rhoda-23-telluraporphyrin are strongly deformed in-plane from the rectangular shape typical for porphyrins, due to rhodium(III) coordination preferences, the large size of the two core atoms, and the porphyrin skeleton constrains. These two metallaporphyrins exhibit fluxional behavior, as studied by 1 H NMR and DFT, involving the in-plane motion and the switch of the rhodium center(s) between two nitrogen donors. A side product detected in the reaction mixture, 21-oxa-23-rhodaporphyrin, results from tellurium-to-oxygen exchange, occurring in parallel to the tellurium-to-rhodium exchange. The reaction paths and mechanisms have been analyzed. The title 21,23-dirhodaporphyrin contains a bridged bimetallic unit, Rh2 Cl2 , in the center of the macrocycle, with two rhodium(III) ions lying approximately in the plane of the porphyrinoid skeleton. The geometry of the implanted Rh2 Cl2 unit is affected by macrocyclic constrains.

Chemistry inside a Porphyrin Skeleton: Platinacyclopentadiene from Tellurophene.

Platinum(II) binds to 21,23-ditelluraporphyrin forming a side-on complex, which can be easily transformed into an aromatic metallaporphyrin, that is, 21-platina-23-telluraporphyrin, with a platinacyclopentadiene unit built in the porphyrin skeleton in place of one pyrrole ring. The central platinum(II) ion with a CCNTe square-planar coordination sphere can be oxidized to platinum(IV) by chlorine, bromine, methyl iodide or allyl chloride to yield octahedral complexes. All platinatelluraporphyrins show dynamic behavior involving the platinum ion coordination sphere fluxionality and the porphyrin skeleton deformation, both in-plane and out-of-plane, as demonstrated by 1 H NMR spectroscopy.

New anticandidal Cu(i) complexes with neocuproine and ketoconazole derived diphenyl(aminomethyl)phosphane: luminescence properties for detection in fungal cells.

The search for new antifungals is very important because the large genetic variation of pathogenic organisms has resulted in the development of increasingly effective defense mechanisms by microorganisms. Metal complexes as potential drugs are nowadays gaining interest, because they are characterized by accessible redox states of metal centers and a plethora of easily modifiable geometries. In this work we present two new copper(i) iodide or thiocyanide complexes with 2,9-dimethyl-1,10-phenanthroline (dmp) and a diphenylphosphane derivative of ketoconazole (KeP), where a ketoconazole acetyl group is replaced by the -CH2PPh2 unit, [CuI(dmp)KeP] (1-KeP) and [CuNCS(dmp)KeP] (2-KeP) - their synthesis and structural characteristics. The analysis of the intrinsic fluorescence of the ketoconazole moiety in the coordinated KeP molecule revealed that the copper(i) central atom does not act as a quencher and the observed decrease of fluorescence intensity is a result of a strong inner filter effect caused by the presence of the CuXdmp unit. Moreover, the complexes exhibit a remarkable MLCT (metal-ligand charge transfer) based phosphorescence with the emission maximum at 600-615 nm in aqueous media, which probably results from the formation of dimers and higher order oligomers in the most polar solutions. Both complexes proved to be promising antifungal agents towards Candida albicans, showing a relatively high efficiency towards the fluconazole resistant strains with -CDR1 and CDR2 or MDR1 efflux pump overexpression, which suggests that they overcome at least partially these defense mechanisms. Simulations of docking to the cytochrome P450 14α-demethylase (the azoles' primary molecular target) suggested that the compounds studied were rather incapable of competitively inhibiting this enzyme, unlike ketoconazole and the KeP ligand. On the other hand, the phosphorescence in aqueous solutions allowed recording the confocal micrographs of the complexes which showed that both of them are situated in spherical structures inside the cells, most likely in the vacuoles.

Conformation-Dependent Response to the Protonation of Diphenanthrioctaphyrin(1.1.1.0.1.1.1.0): A Route to Pseudorotaxane-Like Structures.

Diphenanthrioctaphyrin(1.1.1.0.1.1.1.0), an expanded carbaporphyrinoid incorporating two phenanthrenylene moieties, exists as two separate, yet interconvertible, locked stereoisomers. These species demonstrate complex dynamic behavior upon protonation, consisting in multiple conformational rearrangements and anion-binding events. The formation of one of the final dicationic forms is accompanied by the inclusion of a complex anion(s) within the macrocyclic cavity yielding a pseudorotaxane-like host-guest complex. Protonation with trifluoroacetic or dichloroacetic acids followed by neutralization afforded a conformation-switching cycle, which involves six structurally different species. Analogous acidification with chiral 10-camphorsulfonic acid and subsequent neutralization generated one of the free base stereoisomers with enantiomeric excess. Therefore, it was shown that the simple acid-base chemistry of diphenanthrioctaphyrin can act as stimulus, inducing chirality into the system, allowing for the manipulation of the stereochemical information imprinted into the enantiomers of the macrocycle.

Kinetic versus Thermodynamic Control Over Multiple Conformations of Di-2,7-naphthihexaphyrin(1.1.1.1.1.1).

Di-2,7-naphthihexaphyrin(1.1.1.1.1.1), a non-aromatic carba-analogue of the hexaphyrin(1.1.1.1.1.1), incorporating two built-in 2,7-naphthylene moieties was synthesized as two separate, conformationally locked stereoisomers. Both conformers followed complex protonation pathways involving structurally different species, which can be targeted under kinetic and thermodynamic control. The neutralization of the ultimate dicationic product, accessible from both stereoisomers of the free base, allowed to realize the complex conformational switching cycle involving six structurally different species.

Mixed-Generation PAMAM G3-G0 Megamer as a Drug Delivery System for Nimesulide: Antitumor Activity of the Conjugate Against Human Squamous Carcinoma and Glioblastoma Cells.

Polyhydroxylated dendrimer was synthesized from poly(amidoamine) (PAMAM) dendrimer generation 3 by addition of glycidol (G3gl). G3gl megamer was further modified by binding PAMAM G0 dendrimers by activation of G3gl with p-nitrophenylchloroformate, followed by the addition of excess PAMAM G0 and purification using dialysis. The maximum G0 binding capacity of G3gl was 12 in the case when G0 was equipped with two covalently attached nimesulide equivalents. Nimesulide (N) was converted into N-(p-nitrophenyl) carbonate derivative and fully characterized using X-ray crystallography and spectral methods. Nimesulide was then attached to G0 via a urea bond to yield G02N. The mixed generation G3gl-G02N megamer was characterized using 1H NMR spectroscopy, and its molecular weight was estimated to be 22.4 kDa. The AFM image of G3gl-G02N deposited on mica demonstrated aggregation of nimesulide-covered megamer. The height of the deposited megamer was 8.5 nm. The megameric conjugate with nimesulide was tested in vitro on three human cell lines: squamous cell carcinoma (SCC-15) and glioblastoma (U-118 MG) overexpressing cyclooxygenase-2 (COX-2), and normal skin fibroblasts (BJ). The conjugate efficiently penetrated into all cells and was more cytotoxic against SCC-15 than against BJ. Moreover, the conjugate produced a strong and selective antiproliferative effect on both cancer cell lines (IC50 < 7.5 µM).

Oxygenation of Phenanthriporphyrin and Copper(III) Phenanthriporphyrin: An Efficient Route to Phenanthribilinones.

Photooxidation of copper(III) 5,6-dimethoxyphenathriporphyrin and copper(III) 5,6-dioxophenanthriporphyrin, which contain phenanthrene or dioxophenathrene moieties built into the macrocyclic frameworks, resulted in the regioselective cleavage that afforded organometallic copper(III) complexes of open-chain phenanthribilinone-type acyclic ligands terminated by carbonyl groups. The copper(III) coordinates two carbon atoms of phenantherene (dioxophenanthrene) and two nitrogen atoms of pyrrole and pyrrolone units, preserving the donor sets of the paternal complexes. The primary dioxygen attack is located at the meso carbon atom adjacent to the phenanthrene moiety. Demetalation of copper(III) 21-benzoyl-phenanthribilin-1-one and copper(III) 21-benzoyl-dioxophenanthribilin-1-one yielded mainly two diastereomers [15Z, 20E] and [15Z, 20Z], which differ in the configurations at two Cα-Cmeso double bonds. The regioselectivity of the cleavage, detected in the course of experimental studies, has been substantiated by DFT investigations. The regioselective cleavage of 5,6-dimethoxyphenanthriporphyrin in reaction with basic iron(III) acetate was detected, providing the synthetically efficient methodology to produce 21-benzoyl-dioxophenanthribilin-1-one.

28-Hetero-2,7-Naphthiporphyrins: Horizontal Expansion of the m-Benziporphyrin Macrocycle.

Replacement of the m-phenylene moiety of m-benziporphyrins with the 2,7-naphthalenyl subunit yielded 28-hetero-2,7-naphthiporphyrins-macrocycles that can be considered as expanded carbaporphyrinoids. This group retains some features of parent m-benziporphyrins, but due to larger size and different shape of the macrocyclic cavity, their coordination properties are different. Upon reduction and conformational rearrangement the 28-thia- and 28-selena-2,7-naphthiporphyrin form organophosphorus(V) complexes.