Theoretical Insights into the Metal–Nonmetal Interaction Inside M₂O@<i>C</i>_2<i>v</i>(31922)‑C₈₀ (M = Sc or Gd)

The metal–nonmetal interaction is complicated but significant in organometallic chemistry and metallic catalysis and is susceptible to the coordination surroundings. Endohedral metallofullerene is considered to be an excellent model for studying metal–nonmetal interactions with the shielding effect of fullerenes. Herein, with the detection of ScGdO@C80 in a previous mass spectrum, we studied the effects of metal atoms (Sc and Gd) on the metal–nonmetal interactions of the thermodynamically stable molecules M2O@C2v(31922)-C80 (M = Sc and Gd), where metal atoms M can be the same or different, using density functional theory calculations. The inner metal atom and the fullerene cage show mainly ionic interactions with some covalent character. The Sc atom with higher electronegativity plays a greater important role in the metal–nonmetal interactions than the Gd atom. This study would be useful for the further study of the metal–nonmetal interaction

Design and Discovery of α‑Oximido-arylacetamides as Novel Antifungal Leads

The discovery of novel and easily accessible antifungal compounds is an imperative issue in agrochemical innovation. Our continuing research with the o-aminophenyloxazoline (NHPhOx) scaffold demonstrated the viability of introducing phenylacetamides for identifying novel antifungal leads. An antifungal function-oriented molecular evaluation was conducted for the previously identified lead R-LE008. Fine-tuning of the α-position and scaffold hopping of acid segment and NHPhOx enables α-oximido-arylacetamide as a novel antifungal model. The concomitant function-oriented diversification produces a panel of antifungal leads CN19, CN21b, CN28, and CN31 against Sclerotinia sclerotiorum and Botrytis cinerea. The crucial and multidimensional effect of the configuration of the acquired amides on the antifungal performance is demonstrated specifically by the separable CN21 isomers. The Z-isomer (CN21b), with an EC50 value of 0.97 μM against B. cinerea, is significantly more potent than its E-isomer (CN21a) and the positive control boscalid. More importantly, compound CN21b can efficiently inhibit resistant B. cinerea strains. CN21b demonstrates a better in vivo preventative effect (82.1%) than those of CN21a (48.1%) and boscalid (55.1%) at 100 μM. CN21b showed a distinct binding model from those of the boscalid and CN21a in the molecular docking simulation. A further morphological investigation by scanning electron microscopy revealed the different mycelia shrinkage of B. cinerea treated by CN21 isomers. The easy accessibility and cost-effectiveness demonstrated the practical potential of α-oximido-phenylacetamide containing NHPhOx as a new model for agrochemical innovation

Design and Discovery of α‑Oximido-arylacetamides as Novel Antifungal Leads

The discovery of novel and easily accessible antifungal compounds is an imperative issue in agrochemical innovation. Our continuing research with the o-aminophenyloxazoline (NHPhOx) scaffold demonstrated the viability of introducing phenylacetamides for identifying novel antifungal leads. An antifungal function-oriented molecular evaluation was conducted for the previously identified lead R-LE008. Fine-tuning of the α-position and scaffold hopping of acid segment and NHPhOx enables α-oximido-arylacetamide as a novel antifungal model. The concomitant function-oriented diversification produces a panel of antifungal leads CN19, CN21b, CN28, and CN31 against Sclerotinia sclerotiorum and Botrytis cinerea. The crucial and multidimensional effect of the configuration of the acquired amides on the antifungal performance is demonstrated specifically by the separable CN21 isomers. The Z-isomer (CN21b), with an EC50 value of 0.97 μM against B. cinerea, is significantly more potent than its E-isomer (CN21a) and the positive control boscalid. More importantly, compound CN21b can efficiently inhibit resistant B. cinerea strains. CN21b demonstrates a better in vivo preventative effect (82.1%) than those of CN21a (48.1%) and boscalid (55.1%) at 100 μM. CN21b showed a distinct binding model from those of the boscalid and CN21a in the molecular docking simulation. A further morphological investigation by scanning electron microscopy revealed the different mycelia shrinkage of B. cinerea treated by CN21 isomers. The easy accessibility and cost-effectiveness demonstrated the practical potential of α-oximido-phenylacetamide containing NHPhOx as a new model for agrochemical innovation

Design and Discovery of α‑Oximido-arylacetamides as Novel Antifungal Leads

The discovery of novel and easily accessible antifungal compounds is an imperative issue in agrochemical innovation. Our continuing research with the o-aminophenyloxazoline (NHPhOx) scaffold demonstrated the viability of introducing phenylacetamides for identifying novel antifungal leads. An antifungal function-oriented molecular evaluation was conducted for the previously identified lead R-LE008. Fine-tuning of the α-position and scaffold hopping of acid segment and NHPhOx enables α-oximido-arylacetamide as a novel antifungal model. The concomitant function-oriented diversification produces a panel of antifungal leads CN19, CN21b, CN28, and CN31 against Sclerotinia sclerotiorum and Botrytis cinerea. The crucial and multidimensional effect of the configuration of the acquired amides on the antifungal performance is demonstrated specifically by the separable CN21 isomers. The Z-isomer (CN21b), with an EC50 value of 0.97 μM against B. cinerea, is significantly more potent than its E-isomer (CN21a) and the positive control boscalid. More importantly, compound CN21b can efficiently inhibit resistant B. cinerea strains. CN21b demonstrates a better in vivo preventative effect (82.1%) than those of CN21a (48.1%) and boscalid (55.1%) at 100 μM. CN21b showed a distinct binding model from those of the boscalid and CN21a in the molecular docking simulation. A further morphological investigation by scanning electron microscopy revealed the different mycelia shrinkage of B. cinerea treated by CN21 isomers. The easy accessibility and cost-effectiveness demonstrated the practical potential of α-oximido-phenylacetamide containing NHPhOx as a new model for agrochemical innovation

Design and Discovery of α‑Oximido-arylacetamides as Novel Antifungal Leads

The discovery of novel and easily accessible antifungal compounds is an imperative issue in agrochemical innovation. Our continuing research with the o-aminophenyloxazoline (NHPhOx) scaffold demonstrated the viability of introducing phenylacetamides for identifying novel antifungal leads. An antifungal function-oriented molecular evaluation was conducted for the previously identified lead R-LE008. Fine-tuning of the α-position and scaffold hopping of acid segment and NHPhOx enables α-oximido-arylacetamide as a novel antifungal model. The concomitant function-oriented diversification produces a panel of antifungal leads CN19, CN21b, CN28, and CN31 against Sclerotinia sclerotiorum and Botrytis cinerea. The crucial and multidimensional effect of the configuration of the acquired amides on the antifungal performance is demonstrated specifically by the separable CN21 isomers. The Z-isomer (CN21b), with an EC50 value of 0.97 μM against B. cinerea, is significantly more potent than its E-isomer (CN21a) and the positive control boscalid. More importantly, compound CN21b can efficiently inhibit resistant B. cinerea strains. CN21b demonstrates a better in vivo preventative effect (82.1%) than those of CN21a (48.1%) and boscalid (55.1%) at 100 μM. CN21b showed a distinct binding model from those of the boscalid and CN21a in the molecular docking simulation. A further morphological investigation by scanning electron microscopy revealed the different mycelia shrinkage of B. cinerea treated by CN21 isomers. The easy accessibility and cost-effectiveness demonstrated the practical potential of α-oximido-phenylacetamide containing NHPhOx as a new model for agrochemical innovation

Insights into the Diels–Alder Reaction of [M₃N@<i>I</i>_<i>h</i>‑C₈₀]^0/1+ (M = Sc or Y): Effects of Oxidation on the Reactivity and Regioselectivity

Diels–Alder (DA) cycloaddition is one important method to generate new derivatives of fullerenes, which is important to accelerating their application. In this study, the DA reaction of 1,3-butadiene and [M3N@Ih-C80]0/1+ (M = Sc and Y) has been investigated by density functional theory calculations to further uncover the effects of different metallic clusters and oxidation states on the reactivity and regioselectivity. 5,6-adduct 2 is thermodynamically most favored for M3N@Ih-C80 (M = Sc and Y) but is less favorable in Y3N@Ih-C80 than in Sc3N@Ih-C80, which arises from the large distortion energy of Y3N@Ih-C80 in 5,6-adduct 2. Further analyses reveal a correlation between the geometrical change of Y3N and the distortion energy of Y3N@Ih-C80. Furthermore, the oxidized endohedral metallofullerenes [M3N@Ih-C80]+ (M = Sc or Y) showing electron-withdrawing characteristics showed higher reactivity, lower regioselectivity, and quite a different reaction mechanism as compared with the neutral one. The theoretical results suggest that strain plays a significant role in the reactivity of [Y3N@Ih-C80]+. The spin density distribution of the 5,6-bond has a considerable influence on the 5,6-addition but little influence on the 6,6-addition

Insights into the Diels–Alder Reaction of [M₃N@<i>I</i>_<i>h</i>‑C₈₀]^0/1+ (M = Sc or Y): Effects of Oxidation on the Reactivity and Regioselectivity

Diels–Alder (DA) cycloaddition is one important method to generate new derivatives of fullerenes, which is important to accelerating their application. In this study, the DA reaction of 1,3-butadiene and [M3N@Ih-C80]0/1+ (M = Sc and Y) has been investigated by density functional theory calculations to further uncover the effects of different metallic clusters and oxidation states on the reactivity and regioselectivity. 5,6-adduct 2 is thermodynamically most favored for M3N@Ih-C80 (M = Sc and Y) but is less favorable in Y3N@Ih-C80 than in Sc3N@Ih-C80, which arises from the large distortion energy of Y3N@Ih-C80 in 5,6-adduct 2. Further analyses reveal a correlation between the geometrical change of Y3N and the distortion energy of Y3N@Ih-C80. Furthermore, the oxidized endohedral metallofullerenes [M3N@Ih-C80]+ (M = Sc or Y) showing electron-withdrawing characteristics showed higher reactivity, lower regioselectivity, and quite a different reaction mechanism as compared with the neutral one. The theoretical results suggest that strain plays a significant role in the reactivity of [Y3N@Ih-C80]+. The spin density distribution of the 5,6-bond has a considerable influence on the 5,6-addition but little influence on the 6,6-addition

Unmasking the Optimal Isomers of Ti₂C₈₄: Ti₂C₂@C₈₂ Instead of Ti₂@C₈₄

Up to now, the controversies over the stable structures of endohedral di-metallofullerenes M₂C<i>_n</i>, whether M₂@C<i>_n</i> or M₂C₂@C_<i>n</i>–2, have continued ceaselessly. Herein, to disclose the optimal structures of Ti₂C₈₄, density functional theory combined with statistical thermodynamic analysis is performed in detail and it turns out that isolated pentagon rule C₈₂ with Ti₂C₂ inserted wins overwhelmingly and performs close-shell electronic structure after our detailed analysis. Furthermore, the stimulation of UV–vis–NIR absorption spectra of thermodynamics preferred isomers under polarizable continuum models shows better accordance to the experimental spectra to reconfirm our result again. And ¹³C NMR spectra of three more stable isomers are performed for further investigations on geometry structures. Last but not least, the electronic structures and various interactions of thermodynamically optimum structures are further revealed

Table1_Xp21 DNA microdeletion syndrome in a Chinese family: clinical features show retinitis pigmentosa and chronic granuloma.DOCX

Xp21 DNA microdeletion syndrome is a very rare disease characterized by retinitis pigmentosa (RP), chronic granulomatous disease (CGD), and McLeod syndrome (MLS). Due to the complex and diverse clinical manifestations, early diagnosis remains a challenge for many physicians. In this study, for the purpose of determining the pathogenic gene variants and definitive diagnosis in a patient medically backgrounded with RP and CGD from a normal Chinese family, whole-exome sequencing (WES) was performed in this proband and copy number variation (CNV) was further verified in other family members by qPCR. A genetic evaluation revealed that the short arm of the X chromosome in the proband had a deletion CNV Xp21.1p11.4 (37431123–38186681) of approximately 0.755 Mb in size, and contained three contiguous OMIM genes as X-linked Kx blood group antigen (XK), cytochrome b-245 beta chain (CYBB), and RP GTPase regulator (RPGR). The qPCR results confirmed the copy number loss in Xp21.1p11.4 present in the proband and his unaffected mother. According to the American College of Medical Genetics and Genomics (ACMG) guidelines for the CNV interpretation, the deletion of this segment was a pathogenic variant. Our results provided evidence that CNV deletion of Xp21.1p11.4 in the short arm of the X chromosome was a pathogenic variant in such Chinese RP and CGD family, and the McLeod phenotype was not yet available. This study suggests that genetic testing is essential for a definitive diagnosis, which should better assist physicians in prediction, diagnosis, genetic counseling, and guidance for Xp21 DNA microdeletion syndrome.</p