C2 Bond Research Articles

Water Participated Dual C(sp3)−C(sp3) Bond Cleavage of Cyclobutanones Catalyzed by Lewis Acid

AbstractLewis acid‐catalyzed ring‐opening reactions of cyclobutanones were mostly achieved through cleavage of a single C2−C3 bond to deliver cyclic products. Herein, an unprecedented Lewis acid catalyzed synergistic cleavage of both C2−C3 bonds in 3‐arylcyclobutanones was realized under participation of water, providing a series of aryl alkyl ketones in mild conditions. A broad scope of substrates decorated with various substituents were well accommodated. Mechanistic proposal including the function of water was unambiguously validated by experimental verification.

Catalytic Intermolecular [4+2]-Cycloaddition toward the Stereo­selective C2–C3 Annulation of Indoles

AbstractCatalytic dearomative cycloaddition involving the C2–C3 bond of indoles is a powerful strategy for the synthesis of fused indoline scaffolds. Through dearomative cycloaddition/annulation, planar indole substrates can be readily transformed into rigid, three-dimensional polycyclic complex structures in one step. Molecules with architectural complexity are generally considered to have drug-like properties. Hence, annulation products have tremendous potential for discovering therapeutic properties, and this strategy has become an important part of the medicinal chemistry toolbox. Using appropriate catalyst control, desirable stereoselectivity can be achieved. Previous literature reports reveal that [3+2]-cycloadditions of indoles have been extensively studied. In contrast, the catalytic [4+2]-cycloaddition/dearomatization of indoles has been much less investigated. In this short review, we focus specifically on six-membered ring annulations via [4+2]-cycloaddition with the C2–C3 bond of indoles and discuss the various catalytic methods that have been developed toward this objective.1 Introduction2 [4+2]-Cycloaddition/Annulation of Indoles2.1 Electron-Rich Indoles2.1.1 Transition-Metal Catalysis2.1.2 Organocatalysis2.2 Electron-Deficient Indoles2.2.1 Transition-Metal Catalysis2.2.2 Organocatalysis3 Summary and Outlook

Abietane diterpenoid salvipisone: Structure elucidation, conformational analysis, and antimicrobial activity

Salvipisone, an abietane diterpenoid, was isolated from the roots of Salvia aethiopis L. using a combination of chromatographic separation techniques. Its structure was elucidated employing a variety of spectroscopic methods, including ultraviolet (UV), infrared (IR), 1D and 2D nuclear magnetic resonance (NMR), and mass spectrometry. A comprehensive analysis of experimental 1D and 2D NMR data, incorporating 1H iterative full spin analysis and higher-order multiplet simulation, revealed discrepancies with previously reported NMR data for this compound. Detailed examination of the 1H NMR spectrum's spin-spin coupling structure provided insights into the relative populations of the three staggered conformers around the C12–C13 bond at room temperature. The conformer populations were determined using the relationship between the experimental values for vicinal coupling constants and the estimated ones for the preferred staggered conformers, yielding a ratio of approx. 80:4:16 for anti, gauche, and gauche′-conformers, respectively. Possible reasons for the observed unevenly populated staggered conformers were also discussed. The antimicrobial activity of salvipisone was evaluated using in vitro and in silico methods. In vitro antimicrobial assays demonstrated that salvipisone exhibited the highest inhibitory effect against Staphylococcus aureus ATCC and Enterococcus faecalis ATCC (MIC = 3.125 μg/mL), followed by Bacillus subtilis ATCC (MIC = 6.25 μg/mL). In contrast, concentrations above 100 μg/mL were necessary to inhibit Escherichia coli ATCC and Klebsiella pneumoniae ATCC. In silico studies suggested that salvipisone, particularly its keto form, has significant potential for inhibiting the enzyme gyrase, highlighting its mechanism of antimicrobial action. Our findings highlight the promising antimicrobial and inhibitory properties of salvipisone, particularly against Gram-positive bacteria such as S. aureus.

Interglycosidic C5–C6 rotamer distributions of alkyl O-rutinosides

The conformational study of carbohydrates is critical to understand the molecular recognition mechanisms underlying their biological functions. Moreover, the systematic study of their conformational patterns can unlock useful tools to design optimized glycomimetics and drug candidates. Using nuclear magnetic resonance, we studied the interglycosidic rotamer equilibria of ester-protected and deprotected alkyl O-rutinosides (α-L-Rha(1,6)β-D-GlcOR). In the protected series, the equilibrium about the C5–C6 bond distributes among the three possible rotamers gg, gt, and tg, being gt the predominant conformer. In these series, the flexibility about C5–C6 shows a marked dependency on the aglycone's structure, where the increase on the aglycone's volume leads to a progressive increment on the tg contributions at the expense of gt, with gg remaining practically constant along the series. The removal of the protective groups results in rutinosides displaying an equilibrium equally distributed between gg and gt with no tg contributions regardless of the aglycone's structure.

Synthesis and antiproliferative activity of (−)-cleistenolide, (6S)-cleistenolide and 4-substituted cleistenolide analogues

A new total synthesis of the natural δ-lactone cleistenolide (1) and its (6S)-stereoisomer 2 was achieved starting from d-glucose. Key steps in the synthesis of 1 involved: oxidative cleavage of the C1–C2 bond in partially protected d-glucose derivative (20), and chain extension of resulting aldehyde 20a with a single C2 fragment using (Z)-selective Wittig olefination. Synthesis of 2 involves the following key steps: periodate cleavage of the C5–C6 bond in the commercially available monoacetone d-glucose (24), followed by C2 chain elongation by using the (Z)-selective Wittig olefination. This new approach is also applied to prepare a few new 4-substituted cleistenolide analogues (3 – 18). Compounds 3 – 7 were designed using molecular hybridization, while the remaining eleven analogues were designed using the bioisosterism method. MTT assay showed that most analogues were more active than lead 1 against several malignant cells, but were completely inactive in the culture of normal foetal lung fibroblasts (MRC-5). The K562 cells appeared to be the most sensitive to the synthesized analogues. The strongest antiproliferative activity against this cell line was shown by 4-O-cinnamoyl derivative 3 and 4,6-di-O-benzyl derivative 17, with submicromolar IC50 values (0.76 and 0.67 μM, respectively). Structural features important for the activity of this class of compounds were identified by SAR analysis.

How Do the Position and Number of Methyl Substituents Affect the Photochemical Process of Criegee Intermediate? Trajectory Surface-Hopping Dynamics of Four-Carbon CIs.

Electronic-structure calculations combined with nonadiabatic trajectory surface-hopping (TSH) dynamic simulations were carried out on two alkenyl-substituted Criegee intermediates (CIs), i.e., propenyl-substituted CI (PCI) and 1-methyl-propenyl substituted CI (MPCI), in order to investigate the influence of the position and number of substituents on the photochemical process of CI in S1 states. It is found that they play critical roles in the reactivity, dominant product channel, and mechanism of the CIs. More specifically, introducing a methyl group on either C1 (α-C) or C3 (γ-C) position of a vinyl-substituted CI (VCI) skeleton facilitates the rotation of the C1═O1 bond and leads to the formation of a three-membered dioxirane ring; meanwhile, it evidently enhances the reactively of the S1-state molecule. Meanwhile, methyl substitution on the vinyl moiety [i.e., C2 (β-C) and C3 (γ-C) positions] is beneficial for the rotation of the C2═C3 bond and thus facilitates the formation of the five-membered 1,2-dioxole ring, and the substitution on C2 site decreases the reactivity. The cosubstitution of C2 and C3 atoms by methyl groups well balances the features of VCI in the sense of high reactivity, consistently predominant channel, and possible dioxole side-product. The findings here not only deepen the knowledge on the photochemical processes of the CI but also inspire the rethinking of the "old" concept of substitution effect.

Biodegradation of flavonoids – Influences of structural features

Flavonoids, a class of natural products with a variety of applications in nutrition, pharmacy and as biopesticides, could substitute more harmful synthetic chemicals that persist in the environment. To gain a better understanding of the biodegradability of flavonoids and the influence of structural features, firstly, the ultimate biodegradation of 19 flavonoids was investigated with the Closed Bottle Test according to the OECD guideline 301 D. Secondly, regarding the fast abiotic degradation reported for several flavonoids with severe concentration decrease within hours and its possible impacts on the processes behind the ultimate biodegradation, primary degradation of 4 selected flavonoids was compared at conditions representing biodegradation, abiotic degradation, and mixed substrates by monitoring the flavonoids' concentrations with HPLC-UV/vis. Our results showed that 17 out of the 19 tested flavonoids were readily biodegradable. Structural features like a hydroxy group at C3, the C2–C3 bond order, a methoxy group in the B ring, and the position of the B ring in regard to the chromene core did not affect biodegradation of the tested flavonoids. Only flavone without any hydroxy groups and morin with an uncommon 2′,4′ pattern of hydroxy groups were non-readily biodegradable. Monitoring the concentration of 4 selected flavonoids by HPLC-UV/vis revealed that biodegradation occurred faster than abiotic degradation at CBT conditions with no other carbon sources present. The presence of an alternative carbon source tends to increase lag phases and decrease biodegradation rates. At this condition, abiotic degradation contributed to the degradation of unstable flavonoids. Overall, as a first tier to assess the environmental fate, our results indicate low risks for persistence of most flavonoids. Thus, flavonoids could represent benign substitutes for persistent synthetic chemicals.

Reaction sites of pyrimidine bases and nucleosides during chlorination: A computational study

As important components of soluble microbial products in water, nucleobases have attracted much attention due to the high toxicity of their direct aromatic halogenated disinfection by-products (AH-DBPs) during chlorination. However, multiple halogenation sites of AH-DBPs pose challenges to identify them. In this study, reaction sites of pyrimidine bases and nucleosides during chlorination were investigated by quantum chemical computational method. The results indicate that the anion salt forms play key roles in chlorination of uracil, thymine, and their nucleosides, while neutral forms make predominant contributions to cytosine and cytidine. In view of both kinetics and thermodynamics, C5 is the most reactive site for uracil and thymine, N3/C5 and N3 for respective uridine and thymidine, N1/C5/N4 and N4 for respective cytosine and cytidine, whose estimated apparent rate constants kobs-est of ∼103, 103/102, 106/102/104, and 103 M−1 s−1, respectively, in consistent with the known experimental results. C6 in all pyrimidine compounds is hardly attacked by Cl+ in HOCl ascribed to its positive charge, but readily attacked by OH‾ in hydrolysis and the N1=C6 bond was found to possess the highest reactivity in hydrolysis among all double bonds. In addition, the structure-kinetic reactivity relationship study reveals a relatively strong correlation between lgkobs-est and APT charge in all pyrimidine compounds rather than FED2 (HOMO). The results are helpful to further understand the reactivity of various reaction sites in aromatic compounds during chlorination.

Radical electron-induced cellulose-semiconductors

Bio-semiconductors are expected to be similar to organic semiconductors; however, they have not been utilized in application yet. In this study, we show the origin of electron appearance, N- and S-type negative resistances, rectification, and switching effects of semiconductors with energy storage capacities of up to 418.5 mJ/m2 using granulated amorphous kenaf cellulose particles (AKCPs). The radical electrons in AKCP at 295 K appear in cellulose via the glycosidic bond C1–O1·–C4. Hall effect measurements indicate an n–type semiconductor with a carrier concentration of 9.89 × 1015/cm3, which corresponds to a mobility of 10.66 cm2/Vs and an electric resistivity of 9.80 × 102 Ωcm at 298 K. The conduction mechanism in the kenaf tissue was modelled from AC impedance curves. The light and flexible cellulose-semiconductors may open up new avenues in soft electronics such as switching effect devices and bio-sensors, primarily because they are composed of renewable natural compounds.

Selective Stereoretention of Carbohydrates upon C−C Cleavage Enabling D‐Glyceric Acid Production with High Optical Purity over a Ag/γ‐Al2O3 Catalyst

AbstractChiral carboxylic acid production from renewable biomass by chemocatalysis is vitally important for reducing our carbon footprint, but remains underdeveloped. We herein establish a strategy that make use of a stereogenic center of biomass to achieve a rare example of D‐glyceric acid production with the highest yield (86.8 %) reported to date as well as an excellent ee value (>99 %). Unlike traditional asymmetric catalysis, chiral catalysts/additives are not required. Ample experiments combined with quantum chemical calculations established the origins of the stereogenic center and catalyst performance. The chirality at C4 in D‐xylose was proved to be retained and successfully delivered to C2 in D‐glyceric acid during C−C cleavage. The remarkable cooperative‐roles of Ag+ and Ag0 in the constructed Ag/γ‐Al2O3 catalyst are disclosed as the crucial contributors. Ag+ was responsible for low‐temperature activation of D‐xylose, while Ag0 facilitated the generation of active O* from O2. Ag+ and active O* cooperatively promoted the precise cleavage of the C2−C3 bond, and more importantly O* allowed the immediate fast oxidization of the D‐glyceraldehyde intermediate to stabilize D‐glyceric acid, thereby inhibiting the side reaction that induced racemization. This strategy makes a significant breakthrough in overcoming the limitation of poor enantioselectivity in current chemocatalytic conversion of biomass.

Biocatalytic Steroidal 9α‐Hydroxylation and Fragmentation Enable the Concise Chemoenzymatic Synthesis of 9,10‐Secosteroids

Abstract9,10‐Secosteroids are an important group of marine steroids with diverse biological activities. Herein, we report a chemoenzymatic strategy for the concise, modular, and scalable synthesis of ten naturally occurring 9,10‐secosteroids from readily available steroids in three to eight steps. The key feature lies in utilizing a Rieske oxygenase‐like 3‐ketosteroid 9α‐hydroxylase (KSH) as the biocatalyst to achieve efficient C9−C10 bond cleavage and A‐ring aromatization of tetracyclic steroids through 9α‐hydroxylation and fragmentation. With synthesized 9,10‐secosteroides, structure–activity relationship was evaluated based on bioassays in terms of previously unexplored anti‐infective activity. This study provides experimental evidence to support the hypothesis that the biosynthetic pathway through which 9,10‐secosteroids are formed in nature shares a similar 9α‐hydroxylation and fragmentation cascade. In addition to the development of a biomimetic approach for 9,10‐secosteroid synthesis, this study highlights the great potential of chemoenzymatic strategies in chemical synthesis.

DFT and Docking Calculations of the Structural, Electronic, Biological and Conductivity Properties of the Synthetic Complex [Cu(hfac)2(L)2][PF6]2

AbstractIn the present research, we report a theoretical study of Cu II complex based on TTF ligand [Cu(hfac)2(L)2][PF6]2 (in neutral and oxidized states +1 and +2, of biological interest and various applications in magnetic conducting materials. It is an organic/inorganic hybrid material involving a coordination between a paramagnetic transition metal and a nitrogenous aromatic TTF linked through a covalent transition conjugate bridge. The optimized structures of neutral and oxidized metal transition complexes obtained using the Density Functional Theory (DFT) method are consistent with the experimental results. Several properties including geometrical parameters, Hirshfeld atomic charges, energies of Frontier Molecular Orbitals (FMOs), and energy gap (ΔEgap) between the Highest Occupied Molecular Orbital (HOMO), and the Lowest Unoccupied Molecular Orbital (LUMO) are calculated for optimized complexes. The results reveal that oxidation leads to more stable aromatic systems and reduces the energy gap. The analysis of the charges as well as the distribution of the spin density in the frontier orbitals shows that the oxidation takes place at the ligand level. More precisely the ylidene C3=C4 bond is the most sensitive molecular part to oxidation. A significant degeneracy of molecular orbitals is also observed. No metallic contribution in the HOMO of Cu complex reveals a strong electronic localization at the end of the chain, and, at the same time a delocalization along the chain, this is also in favor of a good conductivity and excellent catalytic activity of this compounds.

The mechanism of photodegradation reaction of different dissociation forms of tetrabromobisphenol S in water with free radicals and the ecotoxicity evaluation of related products

Tetrabromobisphenol S (TBBPS) is a widely used brominated flame retardant that has attracted environmental concern due to its abundant presence in water. The objective of this study is to systematically analyze the direct photolysis and degradation mechanisms of TBBPS in two different dissociation forms in water, as well as to evaluate their toxicological effects induced by •OH, 1O2, and •NO2 radicals. The degradation mechanism of TBBPS is investigated with density functional theory (DFT) and time-dependent density functional theory (TDDFT) methods, and the toxicity of the degradation products is assessed through toxicological studies. The results of the study indicate that the OH-addition and H-abstraction reactions are favorable pathways for •OH-induced TBBPS degradation. The H-abstraction reaction of TBBPS0 with •OH was more favorable than the •OH addition reaction. However, in the degradation of TBBPS−, the •OH addition reaction was favored over the H-abstraction reaction. Additionally, the indirect photolysis of TBBPS by 1O2 and •NO2 in water was found to be easier for TBBPS− compared to TBBPS0, with degradation mechanisms involving Br-substitution and NO2-addition reactions. The higher Ea values calculated indicate that the degradation of TBBPS by 1O2 and •NO2 in water has been a secondary reaction. The direct photolysis reaction pathway of TBBPS in water has involved the cleavage of the S1–C7 and S1–C16 bonds. For TBBPS0 in the S1/T1 states, the primary reaction pathway is the cleavage of the S1–C16 bond, while for TBBPS−, the primary reaction pathway is the cleavage of the S1–C7 bond. Furthermore, the computational toxicology results indicate a slight increase in the toxicity levels of most products, highlighting the significance of investigating the degradation byproducts of TBBPS in greater detail.

Synthesis of Waixenicin A: Exploring Strategies for Nine-Membered Ring Formation.

We present a comprehensive account on our efforts behind the recently published synthesis of waixenicin A. Our approach for constructing the dihydropyran ring relied on an Achmatowicz rearrangement. For the assembly of the nine-membered ring, four distinct strategies were investigated. Our initial attempts using radical-based addition/fragmentation reactions targeting the C7-C11 bond proved unsuitable for accessing the 6/9-bicycle. By employing anionic fragmentation conditions at the furfuryl alcohol stage, we successfully reached a 5/9-bicycle. However, subsequent ring-expansion was unsuccessful. Alternative approaches, such as Nozaki-Hiyama-Kishi or Heck reactions to connect the C6-C7 bond, also encountered difficulties, with no nine-membered ring formation observed. Our first breakthrough came from our attempts to install the C5-C6 bond via an intramolecular alkylation. Surprisingly, subsequent functional group modifications proved unexpectedly challenging, necessitating a redesign of our synthetic route. Drawing from all our investigations, we concluded that construction of the C9-C10 bond would enable efficient nine-membered ring alkylation and would facilitate the installation of the desired substitution pattern along the southern periphery. Exploration of this strategy yielded further surprises but ultimately led to the successful synthesis of waixenicin A and 9-deacetoxy-14,15-deepoxyxeniculin. For the latter compound, a bioinspired one-step rearrangement to xeniafauranol A was achieved.

Heterologously Expressed Cellobiose Dehydrogenase Acts as Efficient Electron-Donor of Lytic Polysaccharide Monooxygenase for Cellulose Degradation in Trichoderma reesei.

The conversion of lignocellulosic biomass to second-generation biofuels through enzymes is achieved at a high cost. Filamentous fungi through a combination of oxidative enzymes can easily disintegrate the glycosidic bonds of cellulose. The combination of cellobiose dehydrogenase (CDH) with lytic polysaccharide monooxygenases (LPMOs) enhances cellulose degradation in many folds. CDH increases cellulose deconstruction via coupling the oxidation of cellobiose to the reductive activation of LPMOs by catalyzing the addition of oxygen to C-H bonds of the glycosidic linkages. Fungal LPMOs show different regio-selectivity (C1 or C4) and result in oxidized products through modifications at reducing as well as nonreducing ends of the respective glucan chain. T. reesei LPMOs have shown great potential for oxidative cleavage of cellobiose at C1 and C4 glucan bonds, therefore, the incorporation of heterologous CDH further increases its potential for biofuel production for industrial purposes at a reduced cost. We introduced CDH of Phanerochaete chrysosporium (PcCDH) in Trichoderma reesei (which originally lacked CDH). We purified CDH through affinity chromatography and analyzed its enzymatic activity, electron-donating ability to LPMO, and the synergistic effect of LPMO and CDH on cellulose deconstruction. The optimum temperature of the recombinant PcCDH was found to be 45 °C and the optimum pH of PcCDH was observed as 4.5. PcCDH has high cello-oligosaccharide kcat, Km, and kcat/Km values. The synergistic effect of LPMO and cellulase significantly improved the degradation efficiency of phosphoric acid swollen cellulose (PASC) when CDH was used as the electron donor. We also found that LPMO undergoes auto-oxidative inactivation, and when PcCDH is used an electron donor has the function of a C1-type LPMO electron donor without additional substrate increments. This work provides novel insights into finding stable electron donors for LPMOs and paves the way forward in discovering efficient CDHs for enhanced cellulose degradation.

Total Synthesis of Mavacuran Alkaloids via Bioinspired and Non-Bioinspired Strategies

AbstractIn this account, we report our endeavors towards the total synthesis of the mavacuran alkaloids and some of their highly natural complex bis-indoles. Our studies started with the hemisynthesis of voacalgine A and bipleiophylline, made an excursion to a related family of monoterpene indole alkaloids (total synthesis of 17-nor-excelsinidine) and ended with the total syntheses of several mavacuran alkaloids (16-epi-pleiocarpamine, 16-hydroxymethylpleiocarpamine, taberdivarine H, normavacurine, C-mavacurine, C-profluorocurine, and C-fluorocurine) via a combination of bioinspired and non-bioinspired synthetic routes.1 Introduction2 Bioinspired Hemisynthesis of Voacalgine A and Bipleiophylline3 Total Synthesis of the Mavacuran Alkaloids4 Bioinspired Oxidative Cyclization of a Geissoschizine Ammonium Derivative to Form the N1–C16 Bond and the E Ring5 Non-Bioinspired Michael Addition to Form the C15–C20 Bond and the E Ring6 Conclusion7 Epilogue

Cytochrome P450 Mediated Cyclization in Eunicellane Derived Diterpenoid Biosynthesis**

AbstractTerpene cyclization, one of the most complex chemical reactions in nature, is generally catalyzed by two classes of terpene cyclases (TCs). Cytochrome P450s that act as unexpected TC‐like enzymes are known but are very rare. In this study, we genome‐mined a cryptic bacterial terpenoid gene cluster, named ari, from the thermophilic actinomycete strain Amycolatopsis arida. By employing a heterologous production system, we isolated and characterized three highly oxidized eunicellane derived diterpenoids, aridacins A−C (1–3), that possess a 6/7/5‐fused tricyclic scaffold. In vivo and in vitro experiments systematically established a noncanonical two‐step biosynthetic pathway for diterpene skeleton formation. First, a class I TC (AriE) cyclizes geranylgeranyl diphosphate (GGPP) into a 6/10‐fused bicyclic cis‐eunicellane skeleton. Next, a cytochrome P450 (AriF) catalyzes cyclization of the eunicellane skeleton into the 6/7/5‐fused tricyclic scaffold through C2−C6 bond formation. Based on the results of quantum chemical computations, hydrogen abstraction followed by electron transfer coupled to barrierless carbocation ring closure is shown to be a viable mechanism for AriF‐mediated cyclization. The biosynthetic logic of skeleton construction in the aridacins is unprecedented, expanding the catalytic capacity and diversity of P450s and setting the stage to investigate the inherent principles of carbocation generation by P450s in the biosynthesis of terpenoids.

Enantioselectivity in the enzymatic dehydration of malate and tartrate: Mirror image specificities of structurally similar dehydratases.

Malate (2-hydroxysuccinic acid) and tartrate (2,3-dihydroxysuccinic acid) are chiral substrates; the former existing in two enantiomeric forms (R and S) while the latter exists as three stereoisomers (R,R; S,S; and R,S). Dehydration by stereospecific hydrogen abstraction and antielimination of the hydroxyl group yield the achiral products fumarate and oxaloacetate, respectively. Class-I fumarate hydratase (FH) and L-tartrate dehydratase (L-TTD) are two highly conserved enzymes belonging to the iron-sulfur cluster hydrolyase family of enzymes that catalyze reactions on specific stereoisomers of malate and tartrate. FH from Methanocaldococcus jannaschii accepts only (S)-malate and (S,S)-tartrate as substrates while the structurally similar L-TTD from Escherichia coli accepts only (R)-malate and (R,R)-tartrate as substrates. Phylogenetic analysis reveals a common evolutionary origin of L-TTDs and two-subunit archaeal FHs suggesting a divergence during evolution that may have led to the switch in substrate stereospecificity preference. Due to the high conservation of their sequences, a molecular basis for switch in stereospecificity is not evident from analysis of crystal structures of FH and predicted structure of L-TTD. The switch in enantiomer preference may be rationalized by invoking conformational plasticity of the amino acids interacting with the substrate, together with substrate reorientation and conformer selection about the C2C3 bond of the dicarboxylic acid substrates. Although classical models of enzyme-substrate binding are insufficient to explain such a phenomenon, the enantiomer superposition model suggests that a minor reorientation in the active site residues could lead to the switch in substrate stereospecificity.

Synthesis, crystal structure, Hirshfeld surface analysis, DFT, molecular docking and in vitro antitumor studies of (2E)-2-[4-(diethylamino)benzylidene]-N-ethylhydrazinecarbothioamide

The crystal structure and spectral characterization of a new proligand, (2E)-2-[4-(diethylamino)benzylidene]-N-ethylhydrazinecarbothioamide is described. The compound was crystallized in the monoclinic space group P21/c; Z = 8, V = 3192.7(8) Å3 with unit cell parameters a = 26.232(4) Å, b = 7.9196(10) Å, c = 15.369(3) Å,α = 90°, β = 90.217(6)° and γ = 90°. There are two independent molecules in the asymmetric unit. The crystal structure reveals that the compound exists in the thione form and S1 and N2 are at E configuration to each other with respect to N3–C12 bond. Similarly, S2 and N6 are trans to each other with respect to N7–C26 bond in the second molecule of the asymmetric unit. The packing of the molecules in the crystal lattice is stabilized by intermolecular hydrogen bonds, which are quantified with Hirshfeld surface analysis. The synthesized compound was characterized by IR, UV–vis, 1H and 13C NMR spectra. DFT study indicates the molecular chemical stability with a HOMO-LUMO energy gap of 3.79 eV. The molecule is soft with preference for NS coordination mode. The azomethine nitrogen and thione sulfur region are electron rich and can act as a nucleophilic site to bind with the electrophilic regions of DNA or protein receptors. The in silico docking study with 1BNA suggests that the compound can fit comfortably in the curved shape of the DNA target like a minor groove mode of binding. The in vitro cytotoxicity of the compound, which was screened for DLA tumour cells aspirated from the peritoneal cavity of tumor bearing mice, is indicative of its antitumor potential.

Double Bond Geometric Isomers of Pentaketide Ansamycins from Streptomyces sp. S008.

Six new pentaketide ansamycins, namely, shengliangmycins A-F (1-6, respectively), were obtained from the fermentation products of Streptomyces sp. S008OEslmR2 that was derived by constitutive expression of LAL regulator gene slmR2. The structures of 1-6 were determined through comprehensive spectroscopic analysis and single-crystal X-ray diffraction. Compound 1 has a cis-C6═C7 bond, which is different from that of compounds 2-5. Compounds 3-6 feature a morpholinone structural moiety, whereas 5 is characterized by a pyrazoline ring, which is rare in natural products.