Pairs Of Isomers Research Articles

Yield Ratios of Isomeric Pairs \(^{196m,g}\)Au, \(^{186m,g}\)Ir, and \(^{183m,g}\)Os in the \(^{197}\)Au\((\gamma,xnyp)\) Reactions with 2.5 GeV Bremsstrahlung

The yield ratios of high to low spin states of the 196m,gAu, 186m,gIr, and 183m,gOs isomeric pairs produced by 197Au(γ,xnyp) reactions with a bremsstrahlung end-point energy of 2.5 GeV have been measured. Measurements were performed by the activation method in combination with off-line γ-ray spectrometry. The induced activity of the studied radionuclides was derived from the photo-peak area of the selected γ-ray after making the necessary corrections. The isomeric yield ratios obtained in this work are the first measurement. The relationships between the yield ratios of studied isomeric pairs with the value of high spin states, the spin difference between the high spin states and the target nucleus, and the number of nucleons emitted from the target nucleus are discussed.

Immobilization of Biantennary N-Glycans Leads to Branch Specific Epitope Recognition by LSECtin.

The molecular recognition features of LSECtin toward asymmetric N-glycans have been scrutinized by NMR and compared to those occurring in glycan microarrays. A pair of positional glycan isomers (LDN3 and LDN6), a nonelongated GlcNAc4Man3 N-glycan (G0), and the minimum binding epitope (the GlcNAcβ1-2Man disaccharide) have been used to shed light on the preferred binding modes under both experimental conditions. Strikingly, both asymmetric LDN3 and LDN6 N-glycans are recognized by LSECtin with similar affinities in solution, in sharp contrast to the results obtained when those glycans are presented on microarrays, where only LDN6 was efficiently recognized by the lectin. Thus, different results can be obtained using different experimental approaches, pointing out the tremendous difficulty of translating in vitro results to the in vivo environment.

Antimicrobial Activity of Silver Nanoparticles Loaded Biomimetic Isomeric Short Lipopeptide Nanostructures

AbstractLipopeptide‐inspired lipidation of two short tripeptides, Phe‐Tyr‐β‐Ala and Tyr‐Phe‐β‐Ala leads to a pair of constitutional isomers of short peptide amphiphile (sPA). These two molecules were able to mimic lipopeptides properties and therefore could be used as potential drug delivery vehicles up to target sites. Further, these isomeric peptide amphiphiles were able to synthesize stable silver nanoparticles (AgNPs) in presence of sunlight without using any reducing agents. Interestingly, the presence of AgNPs significantly controls the secondary structures of these two isomeric sPAs and hence their self‐assembly. Therefore, such AgNPs‐sPA nanostructures are further used to develop antibacterial materials. Various microscopy and spectroscopy techniques were used to characterize these nanostructures. The antibacterial analysis demonstrated that owing to high biocompatibility and less cytotoxicity, designed sPA exhibited great potential in locally addressing bacterial infections. Thus, such a strategic design of lipidated tripeptide fragments can be tuned for potential therapeutic value for future applications.

Determination of 32 oxidative dyes by high performance liquid chromatography and confirmation by high performance liquid chromatography-tandem mass spectrometry

染发类产品中氧化型染料种类多,实际样品测定时干扰多,建立染发类产品中多种常用染料的测定方法,为该类产品的有效监管提供技术手段十分必要。该研究根据染料使用频率分组,采用能够屏蔽硅羟基和金属离子影响的C18柱,优化了《化妆品安全技术规范》(2015年版)中32种染料的高效液相色谱法(HPLC)并建立了高效液相色谱-串联质谱(HPLC-MS/MS)确证方法。样品以10 g/L亚硫酸氢钠水溶液为抗氧化剂,用无水乙醇-水(1∶1, v/v)混合溶液冰浴超声提取10 min。HPLC方法采用甲醇、乙腈和磷酸盐缓冲液为流动相分两个液相色谱条件进行梯度洗脱分离,于280 nm波长下检测,其中一个HPLC条件中的相互干扰组分均在另一个HPLC条件下完全分离,避免了实际样品检测时组分间的干扰,并排除了32种以外的其他15种常用染料的干扰。HPLC-MS/MS方法分别采用5 mmol/L乙酸铵水溶液-乙腈和5 mmol/L乙酸水溶液-乙腈为正离子和负离子模式下的流动相,电喷雾离子模式下用多反应监测(MRM)模式进行定性和定量分析。HPLC和HPLC-MS/MS两个方法中,日内精密度和48 h内稳定性的相对标准偏差(RSD)<10%,回收率为82.6%~114.9%(RSD<10%)。HPLC方法中32种染料在大约10~500 mg/L范围内线性关系良好(r2>0.99),检出限为9.7~40.1 μg/g; HPLC-MS/MS方法中氢醌线性范围为2.0~79.7 mg/L,检出限为8.0 μg/g,其他组分线性范围约为0.1~4 mg/L,检出限为0.01~0.4 μg/g。采用HPLC、HPLC-MS/MS两个方法和《化妆品安全技术规范》方法同时测定实际样品,共检出16种染料,检出含量范围为58~25160 μg/g。3个方法检测结果的RSD为1.9%~10.1%。该研究增加了HPLC-MS/MS确证方法,适应化妆品法定检验中的未知物确认程序;方法简便快速,结果准确,专属性强,具有较好的通用性和可操作性。

Ion Mobility-Derived Collision Cross-Sections Add Extra Capability in Distinguishing Isomers and Compounds with Similar Retention Times: The Case of Aphidicolanes.

The hyphenation of ion mobility spectrometry with high-resolution mass spectrometry has been widely used in the characterization of various metabolites. Nevertheless, such a powerful tool remains largely unexplored in natural products research, possibly mainly due to the lack of available compounds. To evaluate the ability of collision cross-sections (CCSs) in characterizing compounds, especially isomeric natural products, here we measured and compared the traveling-wave IMS-derived nitrogen CCS values for 75 marine-derived aphidicolanes. We established a CCS database for these compounds which contained 227 CCS values of different adducts. When comparing the CCS differences, 36 of 57 pairs (over 60%) of chromatographically neighboring compounds showed a ΔCCS over 2%. What is more, 64 of 104 isomeric pairs (over 60%) of aphidicolanes can be distinguished by their CCS values, and 13 of 18 pairs (over 70%) of chromatographically indistinguishable isomers can be differentiated from the mobility dimension. Our results strongly supported CCS as an important parameter with good orthogonality and complementarity with retention time. CCS is expected to play an important role in distinguishing complex and diverse marine natural products.

A Data Set of Ion Mobility Collision Cross Sections and Liquid Chromatography Retention Times from 71 Pyridylaminated N-Linked Oligosaccharides

Determination of the glycan structure is an essential step in understanding structure–function relationships of glycans and glycoconjugates including biopharmaceuticals. Mass spectrometry, because of its high sensitivity and mass resolution, is an excellent means of analyzing glycan structures. We previously proposed a method for rapid and precise identification of N-glycan structures by ultraperformance liquid chromatography-connected ion mobility mass spectrometry (UPLC/IM-MS). To substantiate this methodology, we here examine 71 pyridylaminated (PA-) N-linked oligosaccharides including isomeric pairs. A data set on collision drift times, retention times, and molecular mass was collected for these PA-oligosaccharides. For standardization of the observables, LC retention times were normalized into glucose units (GU) using pyridylaminated α-1,6-linked glucose oligomers as reference, and drift times in IM-MS were converted into collision cross sections (CCS). To evaluate the CCS value of each PA-oligosaccharide, we introduced a CCS index which is defined as a CCS ratio of a target PA-glycan to the putative standard PA-glucose oligomer of the same m/z. We propose a strategy for practical structural analysis of N-linked glycans based on the database of m/z, CCS index, and normalized retention time (GU).

Insight into Isomeric Effect on the Photoluminescence and Mechanoluminescence of Cyanostilbene Derivatives.

Molecular structures, packings, and intermolecular interactions significantly affect the photophysical properties of organic luminogens. In this work, the photoluminescence (PL) and mechanoluminescence (ML) of two pairs of isomers, 1/2 and 3/4, were systematically explored. The fluorescence of crystals 1c and 4c is much brighter than that of their isomers 2c and 3c, respectively. Only 1c is ML-active among all four molecules. Single-crystal structural analysis revealed that isomerization of a substituent group affected their molecular packing and intermolecular interactions. Stronger intermolecular interaction and intact three-dimensional hydrogen-bonded networks were formed only in crystal 1c, which were essential for preventing slippage of molecular layers and generating ML; the other molecules were either lacking π-π interactions or C-H···π interactions. Theoretical calculation suggested that the energy barrier between the Franck-Condon (FC) structure and minimum energy crossing point (MECP) structure of 2/3 was much lower than that of 1/4. Nonradiative decay channels of molecules 2 and 3 were thus more easily activated, which led to their lower quantum yield.

Bioactive constituents from the leaves of Lonicera japonica

Six new isolates including three new alkaloids (1–3), one new secoiridoid glycoside (4) and one new 11-delactonization-secoiridoid glycoside (5), and one new organic acid (6) were identified from the leaves of Lonicera japonica, among which 1 and 2 assigned as a pair of configurational isomers possessed two oxazolidin-2-one fragments connected through NN bond. The structures were elucidated by the NMR data and ICD analysis. All the compounds (1–6) were tested for their antioxidant and hepatoprotective activities using cell models of ABAP-induced HepG2 cell and APAP-induced HepG2 cell by the MTT method. Outstandingly, compound 2 exhibited remarkable antioxidative activity with inhibitory rate of 117.2%, and compounds 2, 4, 6 exhibited significant effects with inhibitory rates of 68.1%, 69.3%, 69.2%, respectively.

DICKINSONIA COSTATA of the Winter Mountains: Features of morphology and ontogenesis

The remains of Ediacaran (Vendian) macrofossils from the Zimnie Gory (Winter Mountains) locality (Russia, southeastern White Sea area) are used to characterize one of the classic animals of the Late Precambrian, Dickinsonia costata. The Zimnie Gory material shows that the body of this species, like that of other species of Dickinsonia, was divided into “half-segments” (isomers) arranged in two rows in alternating order. This makes it possible to classify Dickinsonia as an Ediacaran phylum of Metazoa, Proarticulata. D. costata appeared in the benthic community with a body diameter of about 1 mm and the possible absence of transverse differentiation. D. costata from Zimnie Gory grew to very large sizes, reaching a length of 390 mm and having at least 225 pairs of isomers. During the ontogeny of D. costata, there was a significant change in the shape and relative size of the anterior lobe and a multiple increase in the number of isomers. At the same time, in contrast to other dickinsonias, the general body proportions of D. costata from Zimnie Gory varied slightly towards a slight decrease in the relative width. The addition of new isomers occurred during the entire observed interval of the life cycle of this Dickinsonia. Based on this, the growth pattern of D. costata is defined as allometric and indeterminate.

Modulation of the Fluorination Site on Side-Chain Thiophene Improved Efficiency in All-Small-Molecule Organic Solar Cells.

Fine-tuning the phase-separated morphology is of great importance to achieve efficient all-small-molecule organic solar cells (ASM-OSCs). In this work, a pair of isomers are designed and synthesized, namely, BDT-UF and BDT-DF, in which the fluorine atom in BDT-UF is close to the alkyl chain of side-chain thiophene, while that in BDT-DF is close to the center core. Owing to the noncovalent interaction between fluorine and hydrogen, BDT-DF shows a smaller dihedral angle between the thiophene side chain and the BDT core, which causes better molecular planarity. When mixed with N3, BDT-UF shows better miscibility, higher crystallinity, and more ordered molecule stacking in the blend film. Finally, the device of BDT-DF:N3 gains a power conversion efficiency (PCE) of 14.5%, while that of BDT-UF:N3 shows an increase in Voc, Jsc, and FF and gains a PCE of 15.1%. Our work exhibits a way of adjusting the substitution site of fluorine atoms to improve the PCE of ASM-OSCs.

High-performance thin-layer chromatography – antibacterial assay first reveals bioactive clerodane diterpenes in giant goldenrod (Solidago gigantea Ait.)

The present work introduces a high-performance thin-layer chromatography (HPTLC)–direct bioautography method using the Gram-positive plant pathogenic bacterium, Rhodococcus fascians. The screening and isolation procedure comprised of a non-targeted high-performance thin-layer chromatography-effect-directed analysis (HPTLC–EDA) against Bacillus subtilis, B. subtilis subsp. spizizenii, R. fascians, and Aliivibrio fischeri, a targeted HPTLC–mass spectrometry (MS), and bioassay-guided column chromatographic (preparative flash and semi-preparative HPLC) fractionation and purification. The developed new separation methods enabled the discovery of four bioactive cis-clerodane diterpenes, solidagoic acid H (1), solidagoic acid E (2), solidagoic acid I (3), and solidagoic acid F (4), in the n-hexane extract of giant goldenrod (Solidago gigantea Ait.) leaf for the first time. These compounds were identified by 1D and 2D nuclear magnetic resonance (NMR) spectroscopy. The initially used HPTLC method (chloroform – ethyl acetate – methanol 15:3:2, V/V/V) was changed (to n-hexane – isopropyl acetate – methanol – acetic acid 29:20:1:1, V/V/V/V) to achieve the separation of the closely related isomer pairs (1–2 and 3–4). Compounds 1 and 3 exhibited moderate antibacterial activity against the Gram-positive B. subtilis subsp. spizizenii and R. fascians bacterial strains in microdilution assays with half-maximal inhibitory concentration (IC50) values in the range of 32.3–64.4 µg/mL. The mass spectrometric fragmentation of the isolated compounds was interpreted and their previously published NMR assignments lacking certain resonances were completed.

Non-maximal sensitivity to synchronism in elementary cellular automata: Exact asymptotic measures

Nineteen elementary cellular automata rules (and their conjugation, reflection, reflected-conjugation) have been proven not maximum sensitive to synchronism, i.e. they do not have a different dynamics for each (non-equivalent) block-sequential update schedule (defined as ordered partitions of cell positions). In this work we present exact measurements of the sensitivity to synchronism for these rules, as functions of the size. These exhibit a surprising variety of values and associated proof methods, such as the isomer pairs of rule 128, and the connection to the bisection of Lucas numbers of rule 8.

Design, Synthesis, Bioactivity Evaluation, Crystal Structures, and In Silico Studies of New α-Amino Amide Derivatives as Potential Histone Deacetylase 6 Inhibitors.

Hydroxamate, as a zinc-binding group (ZBG), prevails in the design of histone deacetylase 6(HDAC6) inhibitors due to its remarkable zinc-chelating capability. However, hydroxamate-associated genotoxicity and mutagenicity have limited the widespread application of corresponding HDAC6 inhibitors in the treatment of human diseases. To avoid such side effects, researchers are searching for novel ZBGs that may be used for the synthesis of HDAC6 inhibitors. In this study, a series of stereoisomeric compounds were designed and synthesized to discover non-hydroxamate HDAC6 inhibitors using α-amino amide as zinc-ion-chelating groups, along with a pair of enantiomeric isomers with inverted L-shaped vertical structure as cap structures. The anti-proliferative activities were determined against HL-60, Hela, and RPMI 8226 cells, and 7a and its stereoisomer 13a exhibited excellent activities against Hela cells with IC50 = 0.31 µM and IC50 = 5.19 µM, respectively. Interestingly, there is a significant difference between the two stereoisomers. Moreover, an evaluation of cytotoxicity toward human normal liver cells HL-7702 indicated its safety for normal cells. X-ray single crystal diffraction was employed to increase insights into molecule structure and activities. It was found that the carbonyl of the amide bond is on the different side from the amino and pyridine nitrogen atoms. To identify possible protein targets to clarify the mechanism of action and biological activity of 7a, a small-scale virtual screen using reverse docking for HDAC isoforms (1–10) was performed and the results showed that HDAC6 was the best receptor for 7a, suggesting that HDAC6 may be a potential target for 7a. The interaction pattern analysis showed that the α-amino amide moiety of 7a coordinated with the zinc ion of HDAC6 in a bidentate chelate manner, which is similar to the chelation pattern of hydroxamic acid. Finally, the molecular dynamics simulation approaches were used to assess the docked complex’s conformational stability. In this work, we identified 7a as a potential HDAC6 inhibitor and provide some references for the discovery of non-hydroxamic acid HDAC6 inhibitors.

A multi-dimensional liquid chromatography/high-resolution mass spectrometry approach combined with computational data processing for the comprehensive characterization of the multicomponents from Cuscuta chinensis

Challenges encountered in plant metabolites characterization by liquid chromatography/mass spectrometry can arise from the insufficient chromatography separation, the lack of specific database, and low reliability of identification because of the ubiquitous isomerism. Herein, we present an integral approach, by combining comprehensive off-line two-dimensional liquid chromatography/ion mobility-quadrupole time-of-flight mass spectrometry (2D-LC/IM-QTOF-MS), automatic peak annotation, molecular networking, and collision cross section (CCS) prediction, aimed to improve the resolution and reliability in MS-oriented metabolites characterization. Using the seeds of Cuscuta chinensis as a case, the configuration of an XBridge Amide column of hydrophilic interaction chromatography (HILIC) and a Zorbax SB-Aq column of reversed-phase chromatography (RPC), in an off-line mode, showed the orthogonality of 0.73 and effective peak capacity of 4361. Data-independent high-definition MSE (HDMSE) in the negative mode could enable high-coverage MS2 data acquisition and enhance the ions resolution, while computational peak annotation workflows facilitated by UNIFITM and Global Natural Products Social Molecular Network (GNPS) could efficiently characterize the targeted and untargeted compound analogs. A total of 302 compounds were identified or tentatively characterized, and 109 thereof were unreported. Moreover, CCS prediction (www.allccs.zhulab.cn) provided more possibilities to distinguish 12 pairs of isomers in the lack of reference standards. The 2D-LC/IM-QTOF-MS approach enabled the collection of five dimension of data related to each component (tR by HILIC and RPC, CCS, m/z in MS1 and MS2), and the intelligent metabolites characterization with more reliable MS data. Conclusively, the established integral strategy can be utilized in metabolome analysis to support the quality control of herbal medicines.

Hepatic Organoid-Based High-Content Imaging Boosts Evaluation of Stereoisomerism-Dependent Hepatotoxicity of Stilbenes in Herbal Medicines.

The complexity of chemical components of herbal medicines often causes great barriers to toxicity research. In our previous study, we have found the critical divergent hepatotoxic potential of a pair of stilbene isomers in a famous traditional Chinese herb, Polygonum multiflorum (Heshouwu in Chinese). However, the high-throughput in vitro evaluation for such stereoisomerism-dependent hepatotoxicity is a critical challenge. In this study, we used a hepatic organoids–based in vitro hepatotoxic evaluation system in conjunction with using high content imaging to differentiate in vivo organ hepatotoxicity of the 2,3,5,4′-tetrahydroxy-trans-stilbene-2-O-β-glucoside (trans-SG) and its cis-isomer (cis-SG). By using such an organoid platform, we successfully differentiated the two stereoisomers’ hepatotoxic potentials, which were in accordance with their differences in rodents and humans. The lesion mechanism of the toxic isomer (cis-SG) was further found as the mitochondrial injury by high-content imaging, and its hepatotoxicity could be dose-dependently inhibited by the mitochondrial protective agent. These results demonstrated the utility of the organoids-based high-content imaging approach in evaluating and predicting organ toxicity of natural products in a low-cost and high-throughput way. It also suggested the rationale to use long-term cultured organoids as an alternative toxicology platform to identify early and cautiously the hepatotoxic new drug candidates in the preclinical phase.

Investigations of Bis(alkylthiocarbamato)copper Linkage Isomers

Linkage isomers are coordination compounds with the same composition but different donor atoms, resulting in distinct physical and electronic structures. A pair of linkage isomers, CuL555 and CuL465, derived from phenylglyoxal bis(ethylthiocarbamate) were synthesized, isolated, and characterized by structural, electrochemical, and spectroscopic methods. The isomers are stable in solution under ambient conditions, but CuL465 converts to CuL555 in acid, consistent with quantum-chemical calculations. The complexes were screened against a lung adenocarcinoma cell line (A549) and a nonmalignant lung fibroblast cell line (IMR-90) to evaluate the antiproliferation activity. CuL555 and CuL465 possessed EC50 values of 0.113 ± 0.030 and 0.115 ± 0.038 μM for A549 and 1.87 ± 0.29 and 0.77 ± 0.22 μM for IMR-90, respectively.

Comparative analysis of the chemical constituents and in vitro antioxidant activities of different aqueous extracts of Cistanche phelypaea (L.) Cout. from Algeria

• Different aqueous extracts were prepared from Cistanche phelypaea roots. • Decoction presented the highest total phenolic content. • Identical qualitative chromatographic patterns were observed for all extracts. • Quantitative variations were highlighted in some of the identified compounds. • Cold maceration gave the extract with the weakest ferric reducing power activity. Cistanches herba are well-known for their nutritional and therapeutic effects, but only few reports are available about the species Cistanche phelypaea (L.) Cout. and studies of aqueous extracts are scarce. This study aimed to elucidate the impact of aqueous extraction methods including decoction, infusion and cold maceration from C. phelypaea roots on phytochemical composition and in vitro antioxidant activities of the extracts. In order to accomplish this, determinations of total phenolic and flavonoid contents, liquid chromatography electrospray ionization mass spectrometry (LC/ESI-MS and LC/ESI-MS/MS) analyses and in vitro antioxidant activity studies were carried out. All extracts had significant levels of total phenolic content, but the decoction possessed the highest concentration and no significant difference was observed between infusion and cold maceration. Concerning flavonoids, decoction and infusion possessed the highest concentrations. Data obtained from LC/ESI-MS and LC/ESI-MS/MS analyses showed similar qualitative profiles for all aqueous extracts with 14 characteristic chromatographic peaks in negative mode and 6 in positive mode, which allowed the tentative identification of syringin, 14 phenylethanoid glycosides and 5 iridoids, including 5 pairs of isomers. However, significant variations were recorded for the relative abundance of some compounds depending on the method that was employed. Hot extraction procedures, decoction and/or infusion were more efficient in extracting acteoside, isoacteoside and two molecules corresponding to isomers of 2ʹ-acetylacteoside/tubuloside B, and it seems that a longer time of heating-extraction was required for an improved extraction of isoacteoside, and one of the two isomers of 2ʹ-acetylacteoside/tubuloside B, as decoction gave a significant higher amount of these compounds. However, 8-epiloganic acid and cistanoside F, with their respective isomers, and syringin were more extractable by the cold maceration process. All extracts had similar antioxidant properties in scavenging DPPH radical and total antioxidant activity assays, with the exception of the ferric-reducing power activity assay, in which cold maceration exhibited a significantly less potent activity. Aqueous extracts of C. phelypaea roots present an interesting antioxidant potential which is related to the synergistic effects of several antioxidant compounds.

Primary care service use during adolescence and young adulthood: Tertiary care cohort affected by chronic health conditions.

To understand use of family physician services and emergency department visits by adolescents and young adults with chronic health conditions. Longitudinal retrospective observational cohort study using administrative health data. Chronic care clinics at a tertiary care pediatric hospital in Calgary, Alta. In total, 1326 adolescents who were between 12 and 15 years old in 2008, who were observed until 2016, and who received medical services for chronic conditions were enrolled in the study. Eligible participants had at least 4 visits to the same chronic disease clinic in any 2-year window before age 18. Group-based trajectory modeling was used to identify groups of adolescents with distinct patterns of health care use (for visits to emergency departments and to primary care practices), while 2 tests explored trajectory group differences (eg, sex, location of residence). Median age was 14 years (range 12 to 17 years) at study entry, and 22 years (range 14 to 24 years) at study exit. Half were female and most (85.4%) lived in an urban area. Median observation period was 8.7 person-years (range 1.3 to 9.1 years). Group-based trajectory modeling identified 5 distinct trajectory groups of primary care use and 4 groups of emergency services use. Groups differed by sex and location of residence in each trajectory model. Many adolescents increased their use of emergency services between the ages of 12 and 24 years, with distinct patterns of primary care use being observed. Association of additional patient- and system-level factors (eg, disease severity, distance to nearest family physician office) should be explored.

Molecular manipulation of the 1,5,6,7-tetrahydro-4H-indazol-4-one scaffold to obtain new human neutrophil elastase (HNE) inhibitors

Human neutrophil elastase (HNE) is a globular glycoprotein of about 30 kDa belonging to the chymotrypsin family, and it has been recognized as an important target for several inflammatory diseases, in particular related to the respiratory system. Here, we report the development of potent HNE inhibitors using a classic medicinal chemistry approach starting from our previously published pyrazolocyclohexanones. By contraction and enlargement of the cyclohexanone ring, we obtained pyrazolocyclopentanone and pyrazolocycloeptanone derivatives, respectively. Both nuclei were suitable for the synthesis of potent HNE inhibitors, and activity was maintained in the nanomolar range. The inhibitory activity was strongly dependent on the presence of an N-CO function as the point of attachment by HNE Ser195. Spectroscopic techniques, GC-MS, and crystallographic studies allowed us to univocally assign the correct structures to the pairs of isomers (N1 and N2) obtained in the alkylation/acylation reactions. The two isomers N1 and N2 exhibited a comparable potency. Finally, molecular modeling of the most active compound 8e (IC50 = 26 nM) demonstrated that orientation of the molecule was favorable for formation of a Michaelis complex, and the parameter values were in agreement with its potent inhibitory activity.

Structural Isomerization in Cu(I) Clusters: Tracing the Cu Thermal Migration Paths and Unveiling the Structure-Dependent Photoluminescence

Structural Isomerization in Cu(I) Clusters: Tracing the Cu Thermal Migration Paths and Unveiling the Structure-Dependent Photoluminescence