Asymmetric Synthesis of Chiral 2-Cyclohexenones with Quaternary Stereocenters via Ene-Reductase Catalyzed Desymmetrization of 2,5-Cyclohexadienones.

Stereoselective synthesis of quaternary stereocenters represents a significant challenge in organic chemistry. Herein, we describe the use of ene-reductases OPR3 and YqjM for the efficient asymmetric synthesis of chiral 4,4-disubstituted 2-cyclohexenones via desymmetrizing hydrogenation of prochiral 4,4-disubstituted 2,5-cyclohexadienones. This transformation breaks the symmetry of the cyclohexadienone substrates, generating valuable quaternary stereocenters with high enantioselectivities (ee, up to >99%). The mechanistic causes for the observed high enantioselectivities were investigated both experimentally (stopped-flow kinetics) as well as theoretically (quantum mechanics/molecular mechanics calculations). The synthetic potential of the resulting chiral enones was demonstrated in several diversification reactions in which the stereochemical integrity of the quaternary stereocenter could be preserved.

Characterization of Germanium Nanoparticles from Arylgermanium Trihydrides.

Germanium is a promising basis for nanomaterials due to its low toxicity and valuable optical and electronic properties. However, germanium nanomaterials have seen little research compared to other group 14 elements due to unpredictable chemical behavior and high costs. Here, we report the dehydrocoupling of o-tolylgermanium trihydride to amorphous nanoparticles. The reaction is facilitated through reflux at 162 °C and can be accelerated with an amine base catalyst. Through cleavage of both H2 and toluene, new Ge-Ge bonds form. This results in nanoparticles consisting of crosslinked germanium with o-tolyl termination. The particles are 2-6 nm in size and have masses above approximately 3500 Da. The organic substituents are promising for further functionalization. Combined with strong absorption up to 600 nm and moderate solubility and air stability, there are numerous possibilities for future applications.

Highly functionalized diaminocyclopentanes: A new route to potent and selective inhibitors of human O-GlcNAcase.

A new class of compounds inhibiting de-O-glycosylation of proteins has been identified. Highly substituted diaminocyclopentanes are impressively selective reversible non-transition state O-ß-N-acetyl-d-glucosaminidase (O-GlcNAcase) inhibitors. The ease of preparative access and remarkable biological activities provide highly viable leads for the development of anti-tau-phosphorylation agents with a view to eventually ameliorating Alzheimer's disease.

Surface-Initiated Polymerizations Mediated by Novel Germanium-Based Photoinitiators.

Since surface-initiated photopolymerization techniques have gained increasing interest within the last decades, the coupling of photoinitiators to surfaces and particles has become an important research topic in material and surface sciences. In terms of surface modification and functionalization, covalently coupled photoinitiators and subsequent photopolymerizations are employed to provide a huge variety of surface properties, such as wettability, stimulus responsive features, antifouling behavior, protein binding, friction control, drug delivery, and many more. For this purpose, numerous type I and type II photoinitiators or other photosensitive moieties have been attached to different substrates so far. In our studies, a convenient and straightforward synthetic protocol to prepare a novel germanium-based photoinitiator (bromo-tris(2,4,6-trimethylbenzoyl)germane) in good yields was developed. The immobilization of this photoinitiator at the surface of silicon wafers and quartz plates was evidenced by X-ray photoelectron spectroscopy (XPS). Employing visible-light-triggered surface-initiated polymerization of different functional monomers, including acrylamide, perfluorodecyl acrylate, and fluorescein-o-acrylate, surfaces with various features such as hydrophilic/hydrophobic and fluorescent properties were prepared. This was also achieved in a spatially resolved manner. The polymer layers were characterized by contact angle measurements, UV-vis/fluorescence spectroscopy, spectroscopic ellipsometry, and XPS. The thicknesses of the surface grafted polymer layers ranged between 10 and 126 nm.

Magnetostructural Properties of Some Doubly-Bridged Phenoxido Copper(II) Complexes.

Three new tripod tetradentate phenolate-amines (H2L1, H2L4 and H2L9), together with seven more already related published ligands, were synthesized, and characterized. With these ligands, two new dinuclear doubly-bridged-phenoxido copper(II) complexes (3, 4), and six more complexes (1, 2, 5-8), a new trinuclear complex (9) with an alternative doubly-bridged-phenoxido and -methoxido, as well as the 1D polymer (10) were synthesized, and their molecular structures were characterized by spectroscopic methods and X-ray single crystal crystallography. The Cu(II) centers in these complexes exhibit distorted square-pyramidal arrangement in 1-4, mixed square pyramidal and square planar in 5, 6, and 9, and distorted octahedral (5+1) arrangements in 7 and 8. The temperature dependence magnetic susceptibility study over the temperature range 2-300 K revealed moderate-relatively strong antiferromagnetic coupling (AF) (|J| = 289-145 cm-1) in complexes 1-6, weak-moderate AF (|J| = 59 cm-1) in the trinuclear complex 9, but weak AF interactions (|J| = 3.6 & 4.6 cm-1) were obtained in 7 and 8. No correlation was found between the exchange coupling J and the geometrical structural parameters of the four-membered Cu2O2 rings.

Dinuclear doubly bridged phenoxido copper(II) complexes as efficient anticancer agents.

Two cationic [Cu2(L1-2)2](ClO4)2 (1, 2), and four neutral doubly bridged-phenoxido-copper(II) complexes [Cu2(L3-4)2] (3, 4) and [Cu2(L5-6)2(H2O)]‧2H2O (5, 6) as well as 1D polymeric catena-[Cu(L7)] (7), where HL1-2 and H2L3-7 represent tripodal tetradentate pyridyl or aliphatic-amino groups based 2,4-disubstituted phenolates, were synthesized and thoroughly characterized by various spectroscopic methods and single crystal X-ray analysis. The molecular structures of the complexes exhibited diverse geometrical environments around the central Cu(II) atoms. The in vitro antiproliferative activity of the isolated complexes and selected parent free ligands were screened against some human cancer cell lines (A2780, A2780R, PC-3, 22Rv1, MCF-7). The most promising cytotoxicity against cancer cells were obtained for 1-6, while complex 6 was found as the best performing as compared to the reference drug cisplatin. The cytotoxicity study of complex 6 was therefore extended to wider variety of cancer cell lines (HOS, A549, PANC-1, CaCo2, HeLa) and results revealed its significant cytotoxicity on all investigated human cancer cells. The cell uptake study showed that cytotoxicity of 6 (3 µM concentration and 24 h of incubation) against A2780 cells was almost independent from the intracellular levels of copper. The effect of complexes 4, 6 and 7 on cell cycle of A2780 cells indicates that the mechanism of action in these complexes is not only different from that of cisplatin but also different among them. Complex 7 was able to induce apoptosis in A2780 cells, while complexes 4 and 6 did not and on the other hand, they showed considerable effect on autophagy induction and there are some clues that these complexes were able to induce cuproptosis in A2780 cells.

Synthesis and Unusual Reactivity of Acyl-Substituted 1,4-Disilacyclohexa-2,5-dienes.

In continuation of our recent studies on group 14 rings with exocyclic silicon-carbon double bonds, we report here on the synthesis and reactivity of previously unknown acyl-substituted 1,4-disilacyclohexa-2,5-dienes. 1,1,4,4-Tetrakistrimethylsilyl-1,4-disilacyclohexa-2,5-diene 1 cleanly afforded the silyl anion 1-K after addition of 1 equiv of KO t Bu. 1-K subsequently could be reacted with various electrophiles to the expected substitution products including compounds 4 and 5. When photolyzed with λ > 300 nm radiation, 4 and 5 undergo Brook-type 1,3-Si → O migration reactions to generate the corresponding 1,4-disilacyclohexadienes with exocyclic Si=C bonds as the primary products. These metastable silenes only could be characterized in form of appropriate quenching products. The reaction of compound 4 with KO t Bu followed by the addition of 1 equiv of PhMe2SiCl surprisingly gave the silylated 1,4-disilanorbornadiene cages 8 and 9 instead of the expected exocyclic silene. The responsible sila-Peterson-type mechanism could be elucidated by density functional theory calculations at the conductor-like polarizable continuum model (THF) B3LYP-GD3/6-31 + G(d) level and by the isolation and characterization of unstable intermediate products after proper derivatization.

Synthesis and Characterization of a Variety of α,ω-Bisacylpolysilanes-A Study on Reactivity and Accessibility.

In this study, a variety of α,ω-bisacylpolysilanes were synthesized via two synthetic protocols. The first method for obtaining these compounds is based on the substitution reaction of bromine either on silica gel or by the use of silver salts. Surprisingly, instead of the expected bromine substitution product PhC(O)(SiMe2)2C(O)Ph 4a, we found the formation of the diastereomer PhC(O)(SiMe2)2CBrPhOCBrPh(SiMe2)2C(O)Ph 4b indicating a more complex reaction cascade. On the other hand, the phenylated compound 3b yielded the expected bromine substitution product PhC(O)(SiPh2)2C(O)Ph 4c. For the second protocol, we utilized the Corey-Seebach approach to isolate other representatives of this compound class. We found that the substituents at the α-silicon atoms influence the selectivity of the dethioketalization. While the ethylated and phenylated disilanes 5b,c yield the expected bisacyldisilanes 6a,b, the methylated disilane 4a undergoes a BF3-induced Si-Si bond breakage followed by an intermolecular sila-aldol reaction. This hitherto unknown sila-aldol reaction results in the formation of the enantiomer PhC(O)SiMe2C(OMe)PhSiMe2F 6c in excellent yields. All isolated compounds were analyzed by a combination of NMR spectroscopy, ultraviolet-visible (UV-vis) spectroscopy, single-crystal X-ray crystallography, and mass spectrometry. Furthermore, the photochemical pathways of two representative examples (4b,c) were examined.

Correction: Synthesis and characterization of diacylgermanes: persistent derivatives with superior photoreactivity.

Correction for 'Synthesis and characterization of diacylgermanes: persistent derivatives with superior photoreactivity' by Sabrina D. Püschmann et al., Dalton Trans., 2021, 50, 11965-11974, DOI: 10.1039/D1DT02091A.

Synthesis and characterization of diacylgermanes: persistent derivatives with superior photoreactivity.

Acylgermanes are known as highly efficient photoinitiators. In this contribution, we present the synthesis of new diacylgermanes 4a-evia a multiple silyl abstraction methodology. The method outperforms the state-of-the-art approach (Corey-Seebach reaction) towards diacylgermanes in terms of group tolerance and toxicity of reagents. Moreover, these compounds are decorated with bulky mesityl groups in order to improve their storage stability. The isolated diacylgermanes were characterized by multinuclear NMR-, UV-Vis spectroscopy and X-ray crystallography, as well as photolysis experiments (photobleaching) and photo-DSC measurements (photopolymerization behavior). Upon irradiation with an LED emitting at 385 nm, all compounds except for 4a and 4c bleach efficiently with quantum yields above 0.6. Due to their broad absorption bands, the compounds can be also bleached with blue light (470 nm), where especially 4e bleaches more efficiently than Ivocerin®.

Isolable Geminal Bisgermenolates: A New Synthon in Organometallic Chemistry.

We have synthesized the first isolable geminal bisenolates L2 K2 Ge[(CO)R]2 (R=2,4,6-trimethylphenyl (2 a,b), L=THF for (2 a) or [18]-crown-6 for (2 b)), a new synthon for the synthesis of organometallic reagents. The formation of these derivatives was confirmed by NMR spectroscopy and X-ray crystallographic analysis. The UV/Vis spectra of these anions show three distinct bands, which were assigned by DFT calculations. The efficiency of 2 a,b to serve as new building block in macromolecular chemistry is demonstrated by the reactions with two different types of electrophiles (acid chlorides and alkyl halides). In all cases the salt metathesis reaction gave rise to novel Ge-based photoinitiators in good yields.

Synthesis of d-Galactose-Substituted Acylsilanes and Acylgermanes. Model Compounds for Visible Light Photoinitiators with Intriguing High Solubility.

A convenient synthetic method to obtain d-galactose-substituted acylsilanes and acylgermanes is described. These acyl group 14 compounds are easily accessible in good yields. Their structural properties were analyzed by a combination of NMR, single crystal X-ray crystallography, and UV/vis spectroscopy. A d-galactose-substituted tetraacylgermane represents a new interesting visible light photoinitiator based on its absorption properties as well as its high solubility.

Synthesis of Mixed-Functionalized Tetraacylgermanes.

Tetraacylgermanes are known as highly efficient photoinitiators. Herein, the synthesis of mixed tetraacylgermanes 4 a-c and 6 a-e with a nonsymmetric substitution pattern is presented. Germenolates are crucial intermediates of these new synthetic protocols. The synthesized compounds show increased solubility compared with symmetrically substituted tetraacylgermanes 1 a-d. Moreover, these mixed derivatives reveal broadened n-π* absorption bands, which enhance their photoactivity. Higher absorption of these new compounds at wavelengths above 450 nm causes efficient photobleaching when using an LED emitting at 470 nm. The quantum yields are in the range of 0.15-0.57, depending on the nature of the aroyl substituents. On the basis of these properties, mixed-functionalized tetraacylgermanes serve as ideal photoinitiators in various applications, especially in those requiring high penetration depth. The synthesized compounds were characterized by elemental analysis, IR spectroscopy, NMR and CIDNP spectroscopy, UV/Vis spectroscopy, photolysis experiments, and X-ray crystallography. The CIDNP data suggest that the germyl radicals generated from the new tetraacylgermanes preferentially add to the tail of the monomer butyl acrylate. In the case of 6 a-e only the mesitoyl groups are cleaved off, whereas for 4 a-c both the mesitoyl and the aroyl group are subject to α-cleavage.

Synthesis, structure and in vitro antiproliferative effects of alkyne-linked 1,2,4-thiadiazole hybrids including erlotinib- and ferrocene-containing derivatives.

Chemotherapy is an indispensable tool to treat cancer, therefore, the development of new drugs that can treat cancer with minimal side effects and lead to more favorable prognoses is of crucial importance. A series of eleven novel 1,2,4-thiadiazoles bearing erlotinib (a known anticancer agent), phenylethynyl, ferrocenyl, and/or ferrocenethynyl moieties were synthesized in this work and characterized by NMR, IR and mass spectroscopies. The solid-phase structures were determined by single-crystal X-ray diffraction. Partial isomerisation of bis(erlotinib)-1,2,4-thiadiazole into its 1,3,4-thiadiazole isomer, leading to the isolation of a 3 : 2 isomer mixture, was observed and a plausible mechanism for isomerisation is suggested. The in vitro cytostatic effect and the long-term cytotoxicity of these thiadiazole-hybrids, as well as that of erlotinib, 3,5-dichloro-1,2,4-thiadiazole and 3,5-diiodo-1,2,4-thiadiazole were investigated against A2058 human melanoma, HepG2 human hepatocellular carcinoma, U87 human glioma, A431 human epidermoid carcinoma, and PC-3 human prostatic adenocarcinoma cell lines. Interestingly, erlotinib did not exhibit a significant cytostatic effect against these cancer cell lines. 1,2,4-Thiadiazole hybrids bearing one erlotinib moiety or both an iodine and a ferrocenethynyl group, as well as 3,5-diiodo-1,2,4-thiadiazole demonstrated good to moderate cytostatic effects. Among the synthesized 1,2,4-thiadiazole hybrids, the isomer mixture of bis-erlotinib substituted 1,2,4- and 1,3,4-thiadiazoles showed the most potent activity. This isomer mixture was proven to be the most effective in long-term cytotoxicity, too. 3,5-Diiodo-1,2,4-thiadiazole and its hybrid with one erlotinib fragment were also highly active against A431 and PC-3 proliferation. These novel compounds may serve as new leads for further study of their antiproliferative properties.

Direct X-ray and electron-beam lithography of halogenated zeolitic imidazolate frameworks.

Metal-organic frameworks (MOFs) offer disruptive potential in micro- and optoelectronics because of the unique properties of these microporous materials. Nanoscale patterning is a fundamental step in the implementation of MOFs in miniaturized solid-state devices. Conventional MOF patterning methods suffer from low resolution and poorly defined pattern edges. Here, we demonstrate the resist-free, direct X-ray and electron-beam lithography of MOFs. This process avoids etching damage and contamination and leaves the porosity and crystallinity of the patterned MOFs intact. The resulting high-quality patterns have excellent sub-50-nm resolution, and approach the mesopore regime. The compatibility of X-ray and electron-beam lithography with existing micro- and nanofabrication processes will facilitate the integration of MOFs in miniaturized devices.

Isolable Geminal Bisgermenolates: A New Synthon in Organometallic Chemistry.

We have synthesized the first isolable geminal bisenolates L2K2Ge[(CO)R]2 (R=2,4,6-trimethylphenyl (2 a,b), L=THF for (2 a) or [18]-crown-6 for (2 b)), a new synthon for the synthesis of organometallic reagents. The formation of these derivatives was confirmed by NMR spectroscopy and X-ray crystallographic analysis. The UV/Vis spectra of these anions show three distinct bands, which were assigned by DFT calculations. The efficiency of 2 a,b to serve as new building block in macromolecular chemistry is demonstrated by the reactions with two different types of electrophiles (acid chlorides and alkyl halides). In all cases the salt metathesis reaction gave rise to novel Ge-based photoinitiators in good yields.

Synthesis and characterization of zinc di(O-2,2-dimethylpentan-3-yl dithiocarbonates) bearing pyridine or tetramethylethylenediamine coligands and investigation of their thermal conversion mechanisms towards nanocrystalline zinc sulfide.

Metal xanthates are versatile single source precursors for the preparation of various metal sulfides. In this study, we present the synthesis of the two novel zinc xanthate complexes bis(O-2,2-dimethylpentan-3-yl-dithiocarbonato)(N,N,N',N'-tetramethylethylenediamine)zinc(ii) and bis(O-2,2-dimethylpentan-3-yl-dithiocarbonato)(pyridine)zinc(ii). A thorough investigation of these compounds revealed distinct differences in their structural and thermal properties. While in the complex containing the chelating tetramethylethylenediamine, the xanthate groups coordinate in a monodentate way, they are bidentally coordinated to the zinc atom in the pyridine containing complex. Both compounds show a two-step thermal decomposition with an onset temperature of 151 °C and 156 °C for the tetramethylethylenediamine and pyridine containing complex, respectively. Moreover, different mechanisms are revealed for the two phases of the decomposition based on high resolution mass spectrometry investigations. By the thermal conversion process nanocrystalline zinc sulfide is produced and the coligand significantly influences its primary crystallite size, which is 4.4 nm using the tetramethylethylenediamine and 11.4 nm using the pyridine containing complex for samples prepared at a temperature of 400 °C.

Mechanistic Insights into the Chaperoning of Human Lysosomal-Galactosidase Activity: Highly Functionalized Aminocyclopentanes and C-5a-Substituted Derivatives of 4-epi-Isofagomine.

Glycosidase inhibitors have shown great potential as pharmacological chaperones for lysosomal storage diseases. In light of this, a series of new cyclopentanoid ß-galactosidase inhibitors were prepared and their inhibitory and pharmacological chaperoning activities determined and compared with those of lipophilic analogs of the potent ß-d-galactosidase inhibitor 4-epi-isofagomine. Structure-activity relationships were investigated by X-ray crystallography as well as by alterations in the cyclopentane moiety such as deoxygenation and replacement by fluorine of a "strategic" hydroxyl group. New compounds have revealed highly promising activities with a range of ß-galactosidase-compromised human cell lines and may serve as leads towards new pharmacological chaperones for GM1-gangliosidosis and Morquio B disease.

The Chemistry of Acylgermanes: Triacylgermenolates Represent Valuable Building Blocks for the Synthesis of a Variety of Germanium-Based Photoinitiators.

The formation of a stable triacylgermenolate 2 as a decisive intermediate was achieved by using three pathways. The first two methods involve the reaction of KOtBu or alternatively potassium with tetraacylgermane 1 yielding 2 via one electron transfer. The mechanism involves the formation of radical anions (shown by EPR). This reaction is highly efficient and selective. The third method is a classical salt metathesis reaction toward 2 in nearly quantitative yield. The formation of 2 was confirmed by NMR spectroscopy, UV-vis measurements, and X-ray crystallography. Germenolate 2 serves as a starting point for a wide variety of organo-germanium compounds. We demonstrate the potential of this intermediate by introducing new types of Ge-based photoinitiators 4b-4f. The UV-vis absorption spectra of 4b-4f show considerably increased band intensities due to the presence of eight or more chromophores. Moreover, compounds 4d-4f show absorption tailing up to 525 nm. The performance of these photoinitiators is demonstrated by spectroscopy (time-resolved EPR, laser flash photolysis (LFP), photobleaching (UV-vis)) and photopolymerization experiments (photo-DSC measurements).

Synthesis of Stable Dianionic Cyclic Silenolates and Germenolates.

In this contribution a convenient synthetic method to obtain the previously unknown dianionic cyclic silenolates and germenolates is described. These dianions 2a,b and 4a,b are easily accessible via a one-pot synthetic protocol in high yields. Their structural properties were analyzed by a combination of NMR, single-crystal X-ray crystallography, and DFT quantum mechanical calculations. Moreover, the reactivity of 2a,b and 4a,b with selected examples of electrophiles was investigated. 2a and 4a were reacted with ClSiiPr3 to give new examples of polysilanes and polygermanes with exocyclic double bonds. The reaction of 2b with ClSiMe2SiMe2Cl led to the formation of the acyl bicyclo[2.2.2]octasilane 6. Moreover, the reaction of 2a,b and 4a,b with MeI, as an example of a carbon-centered electrophile, led to selective alkylation reactions at the negatively charged silicon and germanium atoms. The corresponding methylated structures 9a,b and 10a,b were formed in nearly quantitative yields. The competitive reactivity of the silyl and silenolate anion toward 1 equiv of ClSiMe3 showed that the outcome of the reaction was strongly influenced by the substituent at the carbonyl moiety. 2a reacted with 1 equiv of ClSiMe3 to give the corresponding cyclic silenolate S 1 a, which demonstrated that the silyl anion is more nucleophilic than the silenolate with attached aromatic groups. 2b, on the other hand, reacted with 1 equiv of ClSiMe3 to give the bicyclic compound 11 via an intramolecular sila-Peterson alkenation reaction. These findings clearly showed that the alkyl-substituted silenolate is more nucleophilic than the silyl anion. This paper demonstrates that 2a,b and 4a,b have the potential to be used as unique building blocks for complex polysilane and polygermane frameworks.