Fluorination and hydrolytic stability of water-soluble platinum complexes with a borane-bridged diphosphoramidite ligand.

The high fluorophilicity of borane-containing ligands offers promise for accessing new metallodrug candidates capable of bifunctional [18F]-positron emission tomography (PET) imaging, but this requires water soluble and hydrolytically stable ligands that can be fluorinated under mild conditions. Toward this goal, here we report the synthesis and characterization of water-soluble Pt(II) complexes containing a triaminoborane-bridged diphosphoramidite ligand called MeOTBDPhos that can be fluorinated using simple fluoride salts. NMR and XRD studies show that (MeOTBDPhos)PtCl2 (1) dissolves in water with cooperative H-OH addition across the bridgehead N-B bond to form 1-H2O. The B-OH bond in 1-H2O undergoes rapid displacement with fluoride (<10 min) when treated with CsF in MeCN to form 1-HF. 1-HF can also be prepared in <10 min by addition of KF to 1 in the presence Kryptofix® 222 and (HNEt3)Cl in MeCN. In addition to using fluoride salts, we show how mononuclear 1 can be fluorinated with HBF4·Et2O to form dinuclear [(MeOTBDPhos-HF)Pt(µ-Cl)]2(BF4)2 (4-HF). Comparative studies show that the B-F bond in 1-HF undergoes hydrolysis as soon as it is dissolved in water or saline, but the B-F bond persists for hours when the pH of the solution is lowered to pH ≤ 2. In contrast to 1-HF, the B-F bond in dinuclear 4-HF persists for days when dissolved in water, which may be attributed to slow, sacrificial release of fluoride from the BF4- anion. The results show how cooperative N-B reactivity on the ligand can be leveraged to rapidly fluorinate water-soluble MeOTBDPhos complexes under mild conditions and afford suggestions for how to enhance hydrolytic B-F stability, as required for use in biomedical applications.

Programming Rapid Functional Group Diversification into a Solid-State Reaction: Aryl Nitriles for Self-Assembly, Click Reactivity, and Discovery of Coexisting Supramolecular Synthons.

A method to rapidly diversify the molecules formed in organic crystals is introduced, with aryl nitriles playing a novel dual role as both hydrogen-bond acceptors and modifiable organic groups. The discovery of coexisting supramolecular synthons in the same crystal is also described. The general concept is demonstrated by using a bis(aryl nitrile) alkene that undergoes a hydrogen-bond-directed intermolecular [2+2] photodimerization to form a tetra(aryl nitrile)cyclobutane. The product is readily converted by click reactivity to a tetra(aryl tetrazole) and by hydrolysis to a tetra(aryl carboxylic acid). The integration of aryl nitriles into solid-state reactions opens broad avenues to post-modify products formed in crystalline solids for rapid diversification.

Structures and Reactivities of Cocrystals Involving Diboronic Acids and Bipyridines: In Situ Linker Reaction and 1D-to-2D Dimensionality Change via Crystal-to-Crystal Photodimerization.

Cocrystallizations of diboronic acids [1,3-benzenediboronic acid (1,3-bdba), 1,4-benzenediboronic acid (1,4-bdba) and 4,4'-biphenyldiboronic acid (4,4'-bphdba)] and bipyridines [1,2-bis(4-pyridyl)ethylene (bpe) and 1,2-bis(4-pyridyl)ethane (bpeta)] generated the hydrogen-bonded 1 : 2 cocrystals [(1,4-bdba)(bpe)2 ] (1), [(1,4-bdba)(bpeta)2 ] (2), [(1,3-bdba)(bpe)2 (H2 O)2 ] (3) and [(1,3-bdba)(bpeta)2 (H2 O)] (4), wherein 1,3-bdba involved hydrated assemblies. The linear extended 4,4'-bphdba exhibited the formation of 1 : 1 cocrystals [(4,4'-bphdba)(bpe)] (5) and [(4,4'-bphdba-me)(bpeta)] (6). For 6, a hemiester was generated by an in-situ linker transformation. Single-crystal X-ray diffraction revealed all structures to be sustained by B(O)-H⋅⋅⋅N, B(O)-H⋅⋅⋅O, Ow -H⋅⋅⋅O, Ow -H⋅⋅⋅N, C-H⋅⋅⋅O, C-H⋅⋅⋅N, π⋅⋅⋅π, and C-H⋅⋅⋅π interactions. The cocrystals comprise 1D, 2D, and 3D hydrogen-bonded frameworks with components that display reactivities upon cocrystal formation and within the solids. In 1 and 3, the C=C bonds of the bpe molecules undergo a [2+2] photodimerization. UV radiation of each compound resulted in quantitative conversion of bpe into cyclobutane tpcb. The reactivity involving 1 occurred via 1D-to-2D single-crystal-to-single-crystal (SCSC) transformation. Our work supports the feasibility of the diboronic acids as formidable structural and reactivity building blocks for cocrystal construction.

Broomeanamides: Cyclic Octapeptides from an Isolate of the Fungicolous Ascomycete Sphaerostilbella broomeana from India.

The genus Sphaerostilbella comprises fungi that colonize basidiomata of wood-inhabiting fungi, including important forest pathogens. Studies of fermentation cultures of an isolate (TFC201724) collected on the foothills of Himalayas, and closely related to S. broomeana isolates from Europe, led to the identification of a new cyclic octapeptide along with two closely related analogues (1-3) and four dioxopiperazines (4-7). The structure of the lead compound, broomeanamide A (1), was assigned mainly by analysis of 2D NMR and HRESIMS data. The structure consisted of one unit each of N-MeVal, Ala, N-MePhe, Pro, Val, and Ile and two N-MeLeu units. The amino acid sequence was determined on the basis of 2D NMR and HRESIMSMS data. NMR and HRMS data revealed that the other two new peptides have the same amino acid composition except that the Ile unit was replaced with Val in one instance (2) and the N-MeVal unit was replaced with Val in the other (3). The absolute configuration of 1 was assigned by analysis of the acid hydrolysate by application of Marfey's method using both C18 and C3 bonded-phase columns. Broomeanamide A (1) showed antifungal activity against Cryptococcus neoformans and Candida albicans, with MIC values of 8.0 and 64 µg/mL, respectively.

Cubane-forming cyclic dienes that exhibit orthogonal reactivities in the solid state.

Photoirradiation of a binary cocrystal composed of two different cyclic dienes generates a highly-symmetric cubane-like tetraacid cage regioselectively and in quantitative yield. The cage forms by a double [2+2] photodimerization of one of the diene cocrystal components. The second diene while photostable in the cocrystal reacts in a double [2+2] photodimerization as a pure form quantitatively to form a tetramethyl cubane-like cage. The stereochemistry of the cage is structurally authenticated.

Correction: Mechanical rigidity of a shape-memory metal-organic framework increases by crystal downsizing.

Correction for 'Mechanical rigidity of a shape-memory metal-organic framework increases by crystal downsizing' by Al A. Tiba et al., Chem. Commun., 2021, 57, 89-92, DOI: 10.1039/D0CC05684G.

Mechanical rigidity of a shape-memory metal-organic framework increases by crystal downsizing.

Soft porous nanocrystals with a pronounced shape-memory effect exhibit two- to three-fold increase in elastic modulus compared to the microcrystalline counterpart as determined by atomic force microscopy nanoindentation. The increase in rigidity is consistent with the known shape-memory effect displayed by the framework solid at the nanoscale. Crystal downsizing can offer new avenues for tailoring the mechanical properties of metal-organic frameworks.

Supramolecular Sandwiches: Halogen-Bonded Coformers Direct [2+2] Photoreactivity in Two-Component Cocrystals.

The halogen-bond (X-bond) donors 1,3- and 1,4-diiodotetrafluorobenzene (1,3-di-I-tFb and 1,4-di-I-tFb, respectively) form cocrystals with trans-1,2-bis(2-pyridyl)ethylene (2,2'-bpe) assembled by N···I X-bonds. In each cocrystal, 2(1,3-di-I-tFb)·2(2,2'-bpe) and (1,4-di-I-tFb)·(2,2'-bpe), the donor molecules support the C=C bonds of 2,2'-bpe to undergo an intermolecular [2+2] photodimerization. UV irradiation of each cocrystal resulted in stereospecific and quantitative conversion of 2,2'-bpe to rctt-tetrakis(2-pyridyl)cyclobutane (2,2'-tpcb). In each case, the reactivity occurs via face-to-face π-stacked columns wherein nearest-neighbor pairs of 2,2'-bpe molecules lie sandwiched between X-bond donor molecules. Nearest-neighbor C=C bonds are stacked criss-crossed in both cocrystals. The reactivity was ascribed to the olefins undergoing pedal-like motion in the solid state. The stereochemistry of 2,2'-tpcb is confirmed in cocrystals 2(1,3-di-I-tFb)·(2,2'-tpcb) and (1,4-di-I-tFb)·(2,2'-tpcb).

Supramolecular chemistry under mechanochemical conditions: a small molecule template generated and integrated into a molecular-to-supramolecular and back-to-molecular cascade reaction.

We describe the integration of a small-molecule hydrogen-bond-donor template into a cascade reaction that is comprised of a combination of molecular and supramolecular events. The cascade is performed mechanochemically and in the presence of µL amounts of water. The small-molecule template is generated (molecular) using water-assisted vortex grinding and is then used to assemble an alkene (supramolecular) to undergo an intermolecular [2 + 2] photodimerization reaction (molecular). The chemical cascade results in a cyclobutane photoproduct that we show serves as a building block of a hydrogen-bonded network with a topology that conforms to T-silica. Remarkably, the molecular-supramolecular-molecular chemical cascade occurs stepwise and entirely regioselectively within the continuous mechanochemical conditions employed.

Molecular Interpretation of the Compaction Performance and Mechanical Properties of Caffeine Cocrystals: A Polymorphic Study.

The 1:1 caffeine (CAF) and 3-nitrobenzoic acid (NBA) cocrystal (CAF:NBA) displays polymorphism. Each polymorph shares the same docking synthon that connects individual CAF and NBA molecules within the asymmetric unit; however, the extended intermolecular interactions are significantly different between the two polymorphic modifications. These alternative interaction topologies translate to distinct structural motifs, mechanical properties, and compaction performance. To assist our molecular interpretation of the structure-mechanics-performance relationships for these cocrystal polymorphs, we combine powder Brillouin light scattering (p-BLS) to determine the mechanical properties with energy frameworks calculations to identify potentially available slip systems that may facilitate plastic deformation. The previously reported Form 1 for CAF:NBA adopts a 2D-layered crystal structure with a conventional 3.4 Å layer-to-layer separation distance. For Form 2, a columnar structure of 1D-tapes is displayed with CAF:NBA dimers running parallel to the (110) crystallographic direction. Consistent with the layered crystal structure, the shear modulus for Form 1 is significantly reduced relative to Form 2, and moreover, our p-BLS spectra for Form 1 clearly display the presence of low-velocity shear modes, which support the expectation of a low-energy slip system available for facile plastic deformation. Our energy frameworks calculations confirm that Form 1 displays a favorable slip system for plastic deformation. Combining our experimental and computational data indicates that the structural organization in Form 1 of CAF:NBA improves the compressibility and plasticity of the material, and from our tabletability studies, each of these contributions confers superior tableting performance to that of Form 1. Overall, mechanical and energy framework data permit a clear interpretation of the functional performance of polymorphic solids. This could serve as a robust screening approach for early pharmaceutical solid form selection and development.

Cobalt(II) "Scorpionate" complexes as electronic ground state models for cobalt-substituted zinc enzymes: Structure investigation by magnetic circular dichroism.

Zinc centers in pseudo-tetrahedral geometry are widely found in biology, often with three histidine ligands from protein. The trispyrazolylborate "scorpionate" ligand is used as a model for this tris(histidine) motif, and spectroscopically active CoII is often used as a substitute for spectroscopically silent ZnII. In this work, four pseudo-tetrahedral scorpionate complexes with the formula (Tpt-Bu,Tn)CoL, where Tpt-Bu,Tn = hydrotris(3-tert-butyl, 5-2'-thienyl-pyrazol-1-yl)borate anion and L = Cl-, N3-, NCO-, or NCS-, were studied using variable-temperature, variable-field magnetic circular dichroism (VTVH MCD) spectroscopy. The major goal was to determine the axial and rhombic zero field splitting (ZFS) parameters (D and E, respectively) of these S = 3/2 systems and compare these ZFS parameters to those determined previously by high-frequency and -field electron paramagnetic resonance (HFEPR) spectroscopy on the same (L = Cl- and NCS-) or closely related complexes. Additionally, HFEPR studies were undertaken here on the complexes with L = N3-, NCO-. Crystal structures for these two complexes are also first reported here. The values of D determined by VTVH MCD were + 12.8 and + 3.6 cm-1 for the L = Cl- and NCS- complexes, respectively. These values are in close agreement with those for the same complexes as previously determined by HFEPR. The values of D determined by VTVH MCD were + 3.0 and + 6.6 cm-1 for the L = N3- and NCO- complexes, respectively. These values were not as close to those determined by HFEPR in the present study, which are 4.2 cm-1 ≤ |D| ≤ 5.6 cm-1 in Tpt-Bu,TnCoN3, and 8.3 cm-1 ≤ |D| ≤ 11.0 cm-1 in Tpt-Bu,TnCoNCO. The bands in MCD spectra of these complexes were assigned in C3v symmetry and a complete ligand-field analysis of the MCD data was made using the Angular Overlap Model (AOM), which is compared to previous results.

Exploiting Aurophilic Interactions in a [2 + 2] Photocycloaddition: Single-Crystal Reactivity with Changes to Surface Morphology.

A single-crystal-to-single-crystal (SCSC) photodimerization is achieved using Au(I) coordination and aurophilic interactions. The rigid Au2(dppbz)(CF3COO)2 precursor (dppbz = 1,2-bis(diphenylphosphino)benzene) self-assembles with 1,2-trans-bis(4-pyridyl)ethylene (bpe) to afford a discrete [Au4(dppbz)2(bpe)2]4+ macrocycle in the solid state. The alkene undergoes a [2 + 2] photocycloaddition reaction. The photoreaction proceeds via a rare SCSC transformation in quantitative yield that generates [Au4(dppbz)2(4,4'-tpcb)]4+ (4,4'-tpcb = rctt-tetrakis(4-pyridyl)cyclobutane) stereoselectively. Mechanical strain induced by the photoreaction is evidenced by the formation of ramp features on single-crystal surfaces using scanning electron microscopy.

Bioactive Rearrangement Products from Aqueous Photolysis of Pharmaceutical Steroids.

In an ongoing effort to study the environmental fate of endocrine-active steroid hormones, we report the formation of phenolic rearrangement products (3 and 4) with a novel 6,5,8,5-ring system following aqueous photolysis of dienogest (1) and methyldienolone (2). The structures were established by analysis of 2D NMR and HRMS data, and that of 3 was confirmed by X-ray diffraction analysis. These photoproducts exhibit progestogenic and androgenic activity, albeit with less potency than their parent compounds.

Exploiting Boron Coordination: B←N Bond Supports a [2+2] Photodimerization in the Solid State and Generation of a Diboron Bis-Tweezer for Benzene/Thiophene Separation.

B←N coordination supports a [2+2] photodimerization in the solid state. The bond is defined by an orthogonal interaction between stilbazole and a phenylboronic ester to enable a stereocontrolled and rapid photoreaction. The cyclobutane photoproduct affords a novel diboron bis-tweezer adduct that is used to separate a mixture of benzene and thiophene upon crystallization.

Exploiting the Hydrogen-Bonding Capacity of Organoboronic Acids to Direct Covalent Bond Formation in the Solid State: Templation and Catalysis of the [2 + 2] Photodimerization.

The ability of organoboronic acids to direct intermolecular [2 + 2] photodimerizations in the solid state is identified. The reactivity of 1,2-bis(4-pyridyl)ethylene (bpe) within cocrystals of discrete hydrogen-bonded molecular assemblies generates rctt-tetrakis(4-pyridyl)cyclobutane (tpcb) stereoselectively and in up to quantitative yield. Dry grinding of the boronic acids and excess bpe reveal the acids to function as supramolecular catalysts.

Anti-Cryptococcus Phenalenones and Cyclic Tetrapeptides from Auxarthron pseudauxarthron.

Auxarthrones A-E (1-5), five new phenalenones, and two new naturally occurring cyclic tetrapeptides, auxarthrides A (7) and B (8), were obtained from three different solvent extracts of cultures of the coprophilous fungus Auxarthron pseudauxarthron. Auxarthrones C (3) and E (5) possess an unusual 7a,8-dihydrocyclopenta[a]phenalene-7,9-dione ring system that has not been previously observed in natural products. Formation of 1-5 was found to be dependent on the solvent used for culture extraction. The structures of these new compounds were elucidated primarily by analysis of NMR and MS data. Auxarthrone A (1) was obtained as a mixture of chromatographically inseparable racemic diastereomers (1a and 1b) that cocrystallized, enabling confirmation of their structures by X-ray crystallography. The absolute configurations of 7 and 8 were assigned by analysis of their acid hydrolysates using Marfey's method. Compound 1 displayed moderate antifungal activity against Cryptococcus neoformans and Candida albicans, but did not affect human cancer cell lines.

Supramolecular Construction of an Aldehyde-Cyclobutane via the Solid State: Combining Reversible Imine Formation and Metal-Organic Self-Assembly.

A combination of metal-organic self-assembly and reversible imine formation is used to achieve an organic synthesis via the solid state. Imine bond formation is employed to install a pyridyl to the alkene trans-cinnamaldehyde while Ag(I) ions are used in a second step to assemble the pyridyl-functionalized alkene into a geometry in the solid state for an intermolecular [2 + 2] photodimerization. The alkene undergoes the cycloaddition reaction via a 1D coordination polymer to generate a pyridyl-functionalized cyclobutane stereoselectively and in quantitative yield. Removal of the pyridyl group affords the aldehyde-functionalized cyclobutane α-truxilaldehyde.

Haenamindole and fumiquinazoline analogs from a fungicolous isolate of Penicillium lanosum.

Three amino acid-derived compounds, haenamindole (1) and 2'-epi-fumiquinazolines C (2) and D (3), were isolated from cultures of a fungicolous isolate of Penicillium lanosum (MYC-1813=NRRL 66231). Compound 1 was also encountered in cultures of P. corylophilum (MYC-418=NRRL 28126). Structure elucidation of these metabolites was based mainly on high resolution mass spectrometry and NMR data analysis. Haenamindole (1) was found to be a recently reported diketopiperazine-type metabolite that incorporates an unusual ß-Phe unit. Analysis of X-ray crystallographic data and the products of acid hydrolysis of 1 enabled a conclusive, slightly modified stereochemical assignment for haenamindole. Fumiquinazoline analog 2 is a new natural product, while related compound 3 has been previously reported only as a product of an in vitro enzymatic step and of a genetically engineered fungal culture. Compounds 1 and 3 showed antiinsectan activity against the fall armyworm Spodoptera frugiperda.

Talarolutins A-D: Meroterpenoids from an endophytic fungal isolate of Talaromyces minioluteus.

Four meroterpenoids [talarolutins A-D] and one known compound [purpurquinone A] were characterized from an endophytic fungal isolate of Talaromyces minioluteus (G413), which was obtained from the leaves of the medicinal plant milk thistle [Silybum marianum (L.) Gaertn. (Asteraceae)]. The structures of talarolutins A-D were determined by the analysis of various NMR and MS techniques. The relative and absolute configuration of talarolutin A was determined by X-ray diffraction analysis. A combination of NOESY data and comparisons of ECD spectra were employed to assign the relative and absolute configuration of the other analogs. Talarolutins B-D were tested for cytotoxicity against human prostate carcinoma (PC-3) cell line, antimicrobial activity, and induction of quinone reductase; no notable bioactivity was observed in any assay.

Disseminins and Spiciferone Analogues: Polyketide-Derived Metabolites from a Fungicolous Isolate of Pestalotiopsis disseminata.

Seven new polyketide metabolites (disseminins A-E, 1-5, and spiciferones D and E, 7 and 8) were obtained from cultures of a fungicolous isolate of Pestalotiopsis disseminata (NRRL 62562), together with a related compound (6) previously known only as a semisynthetic product. Structures were determined mainly by analysis of HRMS and NMR data. Biogenetically related compounds 1 and 2 possess uncommon bis-tetrahydrofuran and dioxabicyclo[3.2.1]octane ring systems, respectively. X-ray crystallographic analysis of the p-bromobenzoate derivative of 1 confirmed the structure and enabled assignment of its absolute configuration.