Carbonyl Analogues Research Articles

Observation of Aromatic B13(CO)n+ (n = 1-7) as Boron Carbonyl Analogs of Benzene.

CO as a typical σ-donor is one of the most important ligands in chemistry, while planar B13+ is experimentally known as the most prominent magic-number boron cluster analogous to benzene. Joint gas-phase mass spectroscopy, collision-induced dissociation, and first-principles theory investigations performed herein indicate that B13+ reacts with CO successively under ambient conditions to form a series of boron carbonyl complexes B13(CO)n+ up to n = 7, presenting the largest boron carbonyl complexes observed to date with a quasi-planar B13+ core at the center coordinated by nCO ligands around it. Extensive theoretical analyses unveil both the chemisorption pathways and bonding patterns of these aromatic B13(CO)n+ monocations which, with three delocalized π bonds well-retained over the slightly wrinkled B13+ moiety, all prove to be boron carbonyl analogs of benzene tentatively named as boron carbonyl aromatics (BCAs). Their π-isovalent B12(CO)n (n = 1-6) complexes with a quasi-planar B12 coordination center are predicted to be stable neutral BCAs.

A supramolecular approach towards the photorelease of encapsulated caged acids in water: 7-diethylaminothio-4-coumarinyl molecules as triggers.

Herein, we establish the release of aliphatic acids in water upon excitation of 7-diethylaminothio-4-coumarinyl derivatives encapsulated within the organic host octa acid (OA). The 7-diethylaminothio-4-coumarinyl skeleton, employed here as the trigger, photoreleases caged molecules from the excited triplet state, in contrast to its carbonyl analogue, where the same reaction is known to occur from the excited singlet state. Encapsulation in OA solubilizes molecules in water that are otherwise water-insoluble, and retains the used trigger within itself following the release of the aliphatic acid. Such supramolecular characteristics usher in new features to the photorelease methodology. The thiocarbonyl chromophore extends the absorption of coumarinyl trigger to visible range while enhancing the intersystem crossing (ISC) to the triplet state, making it the reactive state. Despite the non-polar environment within the OA capsules the photocleavage occurs in a heterolytic fashion to release the conjugate base and the used trigger as triplet carbocation in an adiabatic process. Interestingly, the triplet carbocation crosses to the ground singlet surface (closed shell singlet carbocation) with the help of water molecules, possibly aided by C = S chromophore. Utilizing the known excited state dynamics of related thiocoumarinyl and coumarinyl systems, we have identified a few of the important mechanistic features of the photorelease process of 7-diethylaminothio-4-coumarinyl derivatives. Ultrafast excited state dynamic studies and quantum chemical calculations planned should help us better understand the photorelease process so as to effectively exploit the proposed system for potential applications.

Microbial transformation of argentatins by Cunninghamella elegans

Microbial biotransformation of argentatin A (1), isoargentatin A (2) and argentatin B (3), the cycloartane- and lanostane-type triterpenoid constituents of guayule (Parthenium argentatum) resin, with Cunninghamella elegans ATCC 9245-A0 afforded eight new metabolites 4–11. These were identified as products formed as a result of: (i) α- and β-hydroxylation at C-7 and C-11; (ii) sequential oxidation of these newly formed alcohols to their corresponding carbonyl analogues; and (iii) rearrangement of the 9(10)-cyclopropane ring. The observed regiospecific hydroxylation reactions are possibly catalyzed by cytochrome P450 enzymes known to be produced by C. elegans. It is interesting that among the biotransformation products 9–11 of argentatin B (3) with a carbonyl group at C-11, only 11 had resulted from the rearrangement of the 9(10)-cyclopropane ring under the conditions used for biotransformation. This constitutes the first report of biotransformation of argentatins by C. elegans.

Strategy to Empower Nontargeted Metabolomics by Triple-Dimensional Combinatorial Derivatization with MS-TDF Software.

Chemical derivatization is a widely employed strategy in metabolomics to enhance metabolite coverage by improving chromatographic behavior and increasing the ionization rates in mass spectroscopy (MS). However, derivatization might complicate MS data, posing challenges for data mining due to the lack of a corresponding benchmark database. To address this issue, we developed a triple-dimensional combinatorial derivatization strategy for nontargeted metabolomics. This strategy utilizes three structurally similar derivatization reagents and is supported by MS-TDF software for accelerated data processing. Notably, simultaneous derivatization of specific metabolite functional groups in biological samples produced compounds with stable but distinct chromatographic retention times and mass numbers, facilitating discrimination by MS-TDF, an in-house MS data processing software. In this study, carbonyl analogues in human plasma were derivatized using a combination of three hydrazide-based derivatization reagents: 2-hydrazinopyridine, 2-hydrazino-5-methylpyridine, and 2-hydrazino-5-cyanopyridine (6-hydrazinonicotinonitrile). This approach was applied to identify potential carbonyl biomarkers in lung cancer. Analysis and validation of human plasma samples demonstrated that our strategy improved the recognition accuracy of metabolites and reduced the risk of false positives, providing a useful method for nontargeted metabolomics studies. The MATLAB code for MS-TDF is available on GitHub at https://github.com/CaixiaYuan/MS-TDF.

Umbrella boronyl cluster B10O: A new candidate for the transition-metal-like bonding model of boron

We report a new candidate B10O with the transition-metal-like boron atom in the boron monoxide clusters family. It adopts an umbrella architecture with a structural configuration of B8-B-BO. Significantly, the central boron atom is coordinated with both arene analog (B8) and carbonyl analog (BO), demonstrating its transition-metal property. Chemical bonding analyses suggest that the upper B9 (B8-B) possesses the double (6σ + 6π) aromaticity, which gives rise to the extraordinary stability of B10O molecular umbrella. As a dynamically stabilized global minimum, the neutral B10O molecular umbrella is promising to be synthesized in the condensed phase.

Boryl Ancillary Ligands: Influencing Stability and Reactivity of Amidinato‐Silanone and Germanone Systems in Ammonia Activation

AbstractWhile the nucleophilic addition of ammonia to ketones is an archetypal reaction in classical organic chemistry, the reactivity of heavier group 14 carbonyl analogues (R2E=O; E=Si, Ge, Sn, or Pb) with NH3 remains sparsely investigated, primarily due to the synthetic difficulties in accessing heavier ketone congeners. Herein, we present a room‐temperature stable boryl‐substituted amidinato‐silanone {(HCDippN)2B}{PhC(tBuN)2}Si=O (Dipp=2,6‐iPr2C6H3) (together with its germanone analogue), formed from the corresponding silylene under a N2O atmosphere. This system reacts cleanly with ammonia in 1,2‐fashion to give an isolable sila‐hemiaminal complex {(HCDippN)2B}{PhC(tBuN)2}Si(OH)(NH2). Quantum chemical calculations reveal that the formation of this sila‐hemiaminal is crucially dependent on the nature of the ancillary ligand scaffold. It is facilitated thermodynamically by the hemi‐lability of the amidinate ligand (which allows for the formation of an energetically critical intramolecular N⋅⋅⋅HO hydrogen bond within the product) and is enabled mech‐anistically by a process in which the silanone initially acts in umpolung fashion as a base (rather than an acid), due to the strongly electron‐releasing and sterically bulky nature of the ancillary boryl ligand.

Boryl Ancillary Ligands: Influencing Stability and Reactivity of Amidinato-Silanone and Germanone Systems in Ammonia Activation.

While the nucleophilic addition of ammonia to ketones is an archetypal reaction in classical organic chemistry, the reactivity of heavier group 14 carbonyl analogues (R2E=O; E=Si, Ge, Sn, or Pb) with NH3 remains sparsely investigated, primarily due to the synthetic difficulties in accessing heavier ketone congeners. Herein, we present a room-temperature stable boryl-substituted amidinato-silanone {(HCDippN)2B}{PhC(tBuN)2}Si=O (Dipp=2,6-iPr2C6H3) (together with its germanone analogue), formed from the corresponding silylene under a N2O atmosphere. This system reacts cleanly with ammonia in 1,2-fashion to give an isolable sila-hemiaminal complex {(HCDippN)2B}{PhC(tBuN)2}Si(OH)(NH2). Quantum chemical calculations reveal that the formation of this sila-hemiaminal is crucially dependent on the nature of the ancillary ligand scaffold. It is facilitated thermodynamically by the hemi-lability of the amidinate ligand (which allows for the formation of an energetically critical intramolecular N⋅⋅⋅HO hydrogen bond within the product) and is enabled mech-anistically by a process in which the silanone initially acts in umpolung fashion as a base (rather than an acid), due to the strongly electron-releasing and sterically bulky nature of the ancillary boryl ligand.

I2-catalyzed tandem sp3 C-H oxidation and annulation of aryl methyl ketones with amidoximes for the synthesis of 5-aroyl-1,2,4-oxadiazoles.

A metal-free, iodine-catalyzed protocol has been developed for constructing biologically significant 5-aroyl 1,2,4-oxadiazole scaffolds using aryl methyl ketones and amidoximes. The strategy produces structurally diverse 5-aroyl 1,2,4-oxadiazoles in good to excellent yields, with a broad substrate scope that includes drug derived substrates. The reaction proceeds through iodine/DMSO-mediated oxidation of aryl methyl ketones, followed by imine formation and subsequent cyclization to yield the desired products. Additionally, this protocol has successfully produced the carbonyl analogs of ataluren and tioxazafen and has facilitated some intriguing late-stage transformations.

Forced degradation studies of elagolix sodium with the implementation of high resolution LC-UV-PDA-MSn (n = 1,2,3…) and NMR structural elucidation

Elagolix sodium (ELS) is a marketed product using to release moderate to severe endometriosis-associated pain. It contains functional groups such as carboxyl group, secondary amino group, 2,4-dioxo pyrimidinyl and several benzyl or benzyl-like position hydrogen atom that are susceptive to occur stress degradation. Forced degradation studies of ELS reveal different degradation profiles of the drug substance which are conducted under photo, thermal, acidic, neutral, alkaline and hydrogen peroxide oxidative conditions in the direction of the ICH guidances. With structural elucidation of LC-PDA/UV-MSn and NMR, the degradants were identified, and seven new degradants are reported in this study. It is confirmed that most of the degradation behaviors of ELS are related to the carboxyl group and secondary amino group in the 3-carboxyl propylamine side chain. Under the oxidative condition using hydrogen peroxide as the oxidant, the secondary amine was oxidized to form an N-hydrogen amine degradant and two further degradants of amine and carbonyl analogs were generated. Under the alkaline degradation condition, the ELS is proven to be stable and no obvious degradants are produced. On the other hand, under the acidic and neutral degradation condition, the 2,4-dioxo pyrimidinyl core of elagolix sodium is stable but the carboxyl group and secondary amine will occur ring cyclization to form the δ-lactam analogs of elagolix sodium. The plausible mechanisms for the degradation of acidic, thermal, photo-degradative and hydrogen peroxide mediated oxidative of elagolix sodium are proposed. It is worth to note that DP-3–4 are the potential degradants which are only found in the solution degradation and are not the real impurities of elagolix sodium.

5,5’-Indigodisulfonic acid as an efficient catalyst for the synthesis of 2,3-dihydroquinazolinone derivatives

An efficient protocol for the synthesis of 2,3-dihydroquinazolinone derivatives from substituted 2-aminobenzamides and carbonyl analog catalyzed by the natural-based 5,5’-indigodisulfonic acid has been developed with good to excellent yields. Compared to the reaction conditions reported before, the use of eco-friendly and recyclable catalysts and mild reaction conditions are the major advantages of the present method.

Novel benzofurane carbonyl analogs of donepezil as acetylcholinesterase inhibitors

Donepezil is the most prescribed drug for mild to moderate Alzheimer's Disease. There is not any alternative drug with this potency yet. New scaffolds bearing benzofurans and amines are being tested for good potency on acetylcholinesterase enzyme to mimic donepezil. In this study, we synthesized 22 novel compounds (2a-b, 3a-t) namely benzofuroyl-phenylpiperazines with 3 step reaction having one microwave green synthesis step at first. Compounds were tested with a modified Ellmann method on cholinesterases. Molecular modeling studies were performed on human acetylcholinesterase X-ray crystal structure complexed with donepezil (4EY7) using Maestro Schrödinger. The most active compounds were subjected to a β-amyloid disaggregation assay. All tested compounds showed good activity (except 3n-p bearing Cl on benzofurane) on acetylcholinesterase (0.98–54 µM) and most of the compounds showed a one-digit IC50, where donepezil was 0.12 µM. The most active compounds according to IC50 values were 3t: 0.98 µM, 3s:1.07 µM, 2b:1.08 µM and 2a: 1.14 µM. Besides, compounds did not show significant activity on butyrylcholinesterase at 100 µM. Molecular modeling studies of compounds showed a good consistency (rmsd=0.45) with the binding mode and interactions of donepezil. 2b, 3 s and 3t exhibited good disaggregation potential on 1–40 β-amyloid. Compound 3t disaggregated more than standard drug rifampicin. Cytotoxicity test results on HEK293 (at 50 µM), showed lower cytotoxicity (except for 3j-k) compared to cisplatin (46% viability). Promisingly, the most active compounds on AChE, 2a-b and 3q-t, showed the lowest cytotoxicity (64–74% viability). Consequently, we have developed potent inhibitors of AChE with close activity to donepezil. For enzyme activity; the presence of methoxy on the aromatic site, ionizable nitrogen group and a carbonyl group on/nearly to main ring (benzofurane) asserted essentially to develop more potent compounds that are equivalent to donepezil.

Redox Activity of Iron Diazine-Diimine Carbonyl and Dinitrogen Complexes: A Comparative Study of the Influence of the Heterocyclic Ring.

A detailed investigation of the electronic structure of diazinediimine iron complexes and their comparison with the pyridine analogues reveals subtle but important differences, imparted by the supporting heterocycle. In the case of LFe(CO)2 complexes (L = pyrazine- and pyrimidinediimine), the characterization of three available redox states confirmed that whereas the nature of the electron-transfer processes is similar, the differences in π-acidity of the supporting heterocycle significantly affect the redox potentials. The reduction of LFe(CO)2 can yield either a ligand-centered radical (for L = pyrimidine) or a C-C-bonded dimer (for L = pyrazine), supported by a dearomatized core. In the latter case, the C-C bond can be reversibly cleaved oxidatively. Compared to the carbonyl analogues, employing weak-field N2 ligands triggers changes in electronic structure for the neutral and reduced LFe(N2) complexes (L = pyrimidinediimine). En route to the synthesis of the nitrogen complexes, the square-planar LFeCl (L = pyrimidinediimine) was isolated. The monoradical character of the supporting chelate triggers the asymmetric distribution of electron density around the heterocycle.

The Role of Low-Energy Electron Interactions in cis-Pt(CO)2Br2 Fragmentation.

Platinum coordination complexes have found wide applications as chemotherapeutic anticancer drugs in synchronous combination with radiation (chemoradiation) as well as precursors in focused electron beam induced deposition (FEBID) for nano-scale fabrication. In both applications, low-energy electrons (LEE) play an important role with regard to the fragmentation pathways. In the former case, the high-energy radiation applied creates an abundance of reactive photo- and secondary electrons that determine the reaction paths of the respective radiation sensitizers. In the latter case, low-energy secondary electrons determine the deposition chemistry. In this contribution, we present a combined experimental and theoretical study on the role of LEE interactions in the fragmentation of the Pt(II) coordination compound cis-PtBr2(CO)2. We discuss our results in conjunction with the widely used cancer therapeutic Pt(II) coordination compound cis-Pt(NH3)2Cl2 (cisplatin) and the carbonyl analog Pt(CO)2Cl2, and we show that efficient CO loss through dissociative electron attachment dominates the reactivity of these carbonyl complexes with low-energy electrons, while halogen loss through DEA dominates the reactivity of cis-Pt(NH3)2Cl2.

Acid–Base Free Main Group Carbonyl Analogues

AbstractMain group carbonyl analogues (R2E=O) derived from p‐block elements (E=groups 13 to 15) have long been considered as elusive species. Previously, employment of chemical tricks such as acid‐ and base‐stabilization protocols granted access to these transient species in their masked forms. However, electronic and steric effects inevitably perturb their chemical reactivity and distinguish them from classical carbonyl compounds. A new era was marked by the recent isolation of acid–base free main group carbonyl analogues, ranging from a lighter boracarbonyl to the heavier silacarbonyls, phosphacarbonyls and a germacarbonyl. Most importantly, their unperturbed nature elicits exciting new chemistry, spanning the vista from classical organic carbonyl‐type reactions to transition metal‐like oxide ion transfer chemistry. In this Review, we survey the strategies used for the isolation of such systems and document their emerging reactivity profiles, with a view to providing fundamental comparisons both with carbon and transition metal oxo species. This highlights the emerging opportunities for exciting “crossover” reactivity offered by these derivatives of the p‐block elements.

Acid-Base Free Main Group Carbonyl Analogues.

Main group carbonyl analogues (R2E=O) derived from p‐block elements (E=groups 13 to 15) have long been considered as elusive species. Previously, employment of chemical tricks such as acid‐ and base‐stabilization protocols granted access to these transient species in their masked forms. However, electronic and steric effects inevitably perturb their chemical reactivity and distinguish them from classical carbonyl compounds. A new era was marked by the recent isolation of acid–base free main group carbonyl analogues, ranging from a lighter boracarbonyl to the heavier silacarbonyls, phosphacarbonyls and a germacarbonyl. Most importantly, their unperturbed nature elicits exciting new chemistry, spanning the vista from classical organic carbonyl‐type reactions to transition metal‐like oxide ion transfer chemistry. In this Review, we survey the strategies used for the isolation of such systems and document their emerging reactivity profiles, with a view to providing fundamental comparisons both with carbon and transition metal oxo species. This highlights the emerging opportunities for exciting “crossover” reactivity offered by these derivatives of the p‐block elements.

On the Nature of the Carbonyl versus Phosphoryl Binding in Uranyl Nitrate Complexes†.

The electronic structure of ligands with phosphoryl and carbonyl binding sites and their complexation behavior with uranyl nitrate were investigated using density functional theory (DFT). The quantum chemical calculations indicate that the electronic charges on both phosphoryl and carbonyl groups are more polarized toward oxygen atoms in isolated ligands. This effect is predominant in the case of complexes of the former. Both P═O and C═O groups are positively charged with the exception in methylisobutylketone (MIBK), where the C=O group is virtually neutral. The fragment molecular orbital analysis suggests that during complexation, a certain amount of charge transfer occurs from the filled pπ-orbitals [πx(CO/PO) and πy(CO/PO)] of the ligand to 5f, 6d, and 7s orbitals of the uranium atom (fσ* and dsσ*). The NBO analysis reaffirms the charge transfer mechanism. The observed red shift in ν(C═O) and ν(P═O) identified in the simulated infrared spectrum of the corresponding complexes implies a moderate weakening of both carbonyl and phosphoryl bonds upon complexation. The atoms in molecules (AIM) analysis suggests a stronger phosphoryl binding compared to carbonyl interactions and an ionic U-O bond. The estimated complexation energies are considerable for phosphoryl ligands compared to those of the carbonyl analogue, with a reasonably large value derived for tri-n-butyl phosphate (TBP). The energy decomposition analysis marked significant stabilizing orbital interactions for phosphoryl ligands. The contributions of estimated dispersion energies are considerable in all complexes and extensively depend on the alkyl unit.

Gemini basic ionic liquid as bi-functional catalyst for the synthesis of 2,3-dihydroquinazolin-4(1H)-ones at room temperature

A cascade synthesis of 2,3-dihydroquinazolin-4(1H)-ones has been developed from 2-aminobenzonitriles and carbonyl analogues using Gemini basic ionic liquid as green catalyst cum solvent at room temperature. Both aldehydes and ketones were condensed with 2-aminobenzonitriles affording good to excellent yields of products. Moreover, the ionic liquids can be reused up to 5th cycle without significant loss of catalytic activity.

Decarboxylative Oxygenation via Photoredox Catalysis

AbstractThe direct conversion of aliphatic carboxylic acids to their dehomologated carbonyl analogues has been accomplished through photocatalytic decarboxylative oxygenation. This transformation is applicable to an array of carboxylic acid motifs, producing ketones, aldehydes, and amides in excellent yields. Preliminary results demonstrate that this methodology is further amenable to aldehyde substrates via in situ oxidation to the corresponding acid and subsequent decarboxylative oxygenation. We have exploited this strategy for the sequential oxidative dehomologation of linear aliphatic chains.

A facile and highly efficient transfer hydrogenation of ketones and aldehydes catalyzed by palladium nanoparticles supported on mesoporous graphitic carbon nitride

A novel transfer hydrogenation methodology for the reduction of ketones (14 examples) and benzaldehyde derivatives (12 examples) to the corresponding alcohols using Pd nanoparticles supported on mesoporous graphitic carbon nitride (mpg-C3N4/Pd) as a reusable catalyst and ammonia borane as a safe hydrogen source in an aqueous solution MeOH/H2O (v/v = 1/1) is described. The catalytic hydrogenation reactions were conducted in a commercially available high-pressure glass tube at room temperature, and the corresponding alcohols were obtained in high yields in 2–5 min. Moreover, the presented transfer hydrogenation protocol shows partial halogen selectivity with bromo-, fluoro-, and chloro-substituted carbonyl analogs. In addition, the present catalyst can be reused up to five times without losing its efficiency, and scaling-up the reaction enables α-methylbenzyl alcohol to be produced in 90% isolated yield.

Going Homoleptic: Synthesis and Full Characterization of Stable Manganese Tetranitrosyl Cation Salts

Although similar to carbon monoxide, the chemistry of homoleptic nitrogen monoxide complexes is fundamentally unexplored compared to their carbonyl analogues. Herein we report the synthesis of the first truly homoleptic transition-metal nitrosyl cation as the salt of the weakly coordinating anions (WCAs) [Al(ORF )4 ]- and [F{Al(ORF )3 }2 ]- (RF =C(CF3 )3 ). These salts are easily accessible in good yields, phase pure, and were fully characterized by IR/Raman, NMR and UV/Vis spectroscopy as well as single-crystal and powder X-ray diffraction. They may serve as unprecedented simple model systems for theoretical and experimental studies of nitrosyl complexes.