Density functional study on the structural conformations and intramolecular charge transfer from the vibrational spectra of the anticancer drug combretastatin‐A2

Combretastatin‐A2 (CA2), a potential anticancer drug in advanced preclinical development, is extracted from the medicinal plant C ombretum caffrum. The NIR‐FT Raman and FT‐IR spectral studies of the molecule were carried out and a b initio calculations performed at the B3LYP/6‐31G(d) level to derive the equilibrium geometry as well as the vibrational wavenumbers and intensities of the spectral bands. The vibrational analysis showed that the molecule has a similar geometry as that of c is‐stilbene, and has undergone steric repulsion resulting in twisting of the phenyl ring with respect to the ethylenic plane. Vibrational analysis was used to investigate the lowering of the stretching modes, and enhancement of infrared band intensities of the C–H stretching modes of Me2 may be attributed to the electronic effects caused by back‐donation and induction from the oxygen atom. Analysis of phenyl ring modes shows that the CA2 stretching mode 8 and the aromatic C–H in‐plane bending mode are equally active as strong bands in both IR and Raman spectra, which can be interpreted as the evidence of intramolecular charge transfer (ICT) between the OH and OCH₃groups via conjugated ring path and is responsible for bioactivity of the molecule. Copyright © 2008 John Wiley & Sons, Ltd.     

Raman spectroscopy of combinatory anticancer drug release from gold nanoparticles inside a single leukemia cell

Combinatory anticancer drug release from gold nanoparticles (AuNPs) in K562 human myeloid leukemia cells was performed using Raman spectroscopy. We fabricated the anticancer drug of imatinib as a BCR‐ABL tyrosine kinase inhibitor on AuNP surfaces along with a transferrin (Tf)‐targeting moiety to treat the leukemia cells. DNA topoisomerase I inhibitor topotecan was also assembled to monitor its fluorescence onto AuNPs. The linker group of 4‐carboxylic benzoic acid was used to conjugate to targeting the Tf protein. Our Raman data indicated that the drug molecules were not detached in the cell culture media but released after treatment with glutathione (2 mM). Intracellular distribution and release of the anticancer drug–AuNP conjugates in K562 cells were examined by both fluorescence microscopy and dark‐field microscopy with surface‐enhanced Raman scattering. Copyright © 2013 John Wiley & Sons, Ltd.     

Vibrational spectra and potential energy distributions for 1‐benzyl‐1H‐imidazole by normal coordinate analysis

The Fourier‐transform (FT) Raman and infrared (IR) spectra of the crystallized novel pharmaceutical molecule 1‐benzyl‐1H‐imidazole (BI) were recorded and analyzed. The geometry, intermolecular hydrogen bond, and harmonic vibrational wavenumbers of BI were investigated with the help of B3PW91 density functional theory (DFT) methods. The detailed interpretation of the vibrational spectra was carried out with the aid of normal coordinate analysis (NCA) following the scaled quantum mechanical force field methodology (SQMFF). The aromaticities of the imidazole and phenyl rings were studied using the standard harmonic oscillator model of aromaticity (HOMA) index. Natural bond orbital (NBO) analysis on BI was carried out to demonstrate the various intramolecular interactions that are responsible for the stabilization of this molecule leading to its medicinal activity. The potential energy profile corresponding to the torsion around the bridge bonds connecting the two rings was drawn to explain the steric and/or electronic effects using potential energy surface (PES) scan studies. The pronounced double‐bond localization in the imidazole ring upon intermolecular H‐bonding appears to be the cause for its enhanced aromaticity. Copyright © 2008 John Wiley & Sons, Ltd.     

The quality control of two Pueraria species using Raman spectroscopy coupled with partial least squares analysis

The dried roots of Pueraria lobata (Puerariae Lobatae Radix; PLR) and Pueraria thomsonii (Puerariae Thomsonii Radix; PTR) are medicinal herbs that are used interchangeably in clinical practice, even though their chemical profiles are different. Therefore, the aim of this study was to develop a rapid and non‐destructive method for the quality control of Pueraria species using Raman spectroscopy in combination with partial least squares analysis. Partial least squares‐discriminant analysis (PLS‐DA) was used to differentiate PLR from PTR, whereas partial least squares regression (PLSR) was used to predict the total phenolic content (TPC) and antioxidant capacities of the Pueraria species. Raman spectroscopy revealed that spectral characteristics of starch and polyphenols differentiated the two species, with the PLS‐DA model giving 100% classification accuracy for the tested samples. A significantly higher TPC (p < 0.001), 2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid) (ABTS) radical scavenging activity (p < 0.001) and cupric reducing antioxidant capacity (CUPRAC; p < 0.001) were observed for PLR as compared to PTR. The high ratio of performance to deviation values (TPC: 9.84; ABTS: 7.11; CUPRAC: 7.13) indicated the PLSR models were robust for predicting TPC and antioxidant capacities. The loading plot revealed that the content of starch and polyphenols were important factors in differentiating PLR from PTR and predicting TPC and antioxidant capacities. The results demonstrate that Raman spectroscopy coupled with chemometrics is a rapid method for the quality control of PLR and PTR. These methods can be applied as a template for the quality control of other herbal medicines and products to promote the correct identification of herbs for clinical practice. Copyright © 2015 John Wiley & Sons, Ltd.     

Evaluation of Raman spectroscopy for prediction of antitumor response to silibinin and its nanoparticulates in DMBA‐induced oral carcinogenesis

Raman spectroscopy is a vibrational spectroscopic technique that can be used to monitor the therapeutic efficacy of anticancer drugs during carcinogenesis in a non‐invasive and label‐free manner. The present study aims to investigate the biochemical changes exerted upon free silibinin (SIL) and its nanoparticulate (SILNPs) treatment against 7,12‐dimethylbenz[a]anthracene (DMBA)‐induced oral carcinogenesis in the fingerprint region of 1800–500 cm⁻¹ using HE‐785 Raman spectrometer. Raman spectra differed significantly between the control and tumor tissues, with tumor tissues characterized by increased intensities of vibrational bands such as nucleic acids, phenylalanine and tryptophan and a lower percentage of lipids when compared to the control tissues. Further, oral administration of free SIL and SILNPs significantly increased lipids and decreased the levels of tryptophan, phenylalanine and nucleic acid contents. Overall, the treatment of nanoparticulate SIL was found to be a more potent antitumor effect than free SIL in preventing the formation of tumor and also brought back the several Raman bands to a normal range in the buccal mucosa of hamsters during DMBA‐induced oral carcinogenesis. In addition, the detailed secondary structure of proteins in the control and experimental groups is also presented. Furthermore, the diagnostic algorithms based on principal component linear discriminant analysis (PC‐LDA) achieved an overall sensitivity of 94–100% and specificity of 76–100%. These results further demonstrate that Raman spectroscopy associated with PC‐LDA diagnostic algorithms could be a valuable tool for rapid and sensitive detection of specific biomolecular changes at the molecular level in response to anticancer drug. Copyright © 2015 John Wiley & Sons, Ltd.     

Content and activity of low-molecular antioxidants in food and medicinal plants

A quantitative analysis of the total content low-molecular antioxidants in extracts from food and medicinal plants with the help of a method based on the interaction of antioxidants with 2,2-diphenyl-1-picrylhydrazyl (DPPH), a stable radical, and of the amperometric method is performed. The results obtained by these two methods exhibit a high correlation (r = 0.96). A comparative analysis of the total content of antioxidants (AOs) in 14 food and medicinal plants and of the activity of these AOs with respect to DPPH was conducted.     

Determination of Arsenic and Mercury in Chinese Medicinal Herbs by Atomic Fluorescence Spectrometry with Closed‐Vessel Microwave Digestion

Abstract

A simple method was developed for the determination of trace arsenic and mercury in Chinese medicinal herbs. The samples were digested in closed‐Teflon vessels in a microwave oven, and followed with hydride generation atomic fluorescence spectrometric measurements. The experimental conditions for the digestion were carefully optimized using an orthogonal design. The accuracy of the method was validated by recovery experiments, and the analytical results for arsenic in seven medicinal herbs (Codonopsis pilosula, Radix angelicae sinensis, Aconitum carmichaeli debx, crude aconite root, giant typhonium rhizome, Rhizoma typhonii, and Radix aconiti lateralis preparata) were found to agree well with those by inductively coupled plasma atomic emission spectrometry (ICP‐AES). The linear dynamic range of the calibration curve was in the range of 0.1–400 ng/mL for arsenic, and the correlation coefficient was better than 0.999. The limit of detection was 0.1 ng/mL for arsenic. For mercury, the determination was accomplished through mercury cold vapor generation in the same instrumental system. The linear dynamic range was 0.03–250 ng/mL, with a limit of detection of 0.03 ng/mL for mercury. This was a rapid, convenient, precise, and cost‐effective method.     

不同产地艾叶35种矿物元素的分析与评价

矿物元素的种类和含量是中药材质量评价的重要指标,与中药材的生长发育、药用物质的形成以及临床疗效的发挥密切相关。中药材矿物元素的分布因产地间气候、土壤、水文等生态因子不同而凸显的质量特征和作用规律是值得探索的问题。以4个省份5个主产区的75份艾叶样品为实验材料,利用电感耦合等离子体质谱法（ICP-MS）和电感耦合等离子体原子发射光谱法（ICP-AES）法测定Ca,K,Mg,Na,Fe,Sn,Be,As,Al,V,Sc,Cr,Mn,Co,Bi,Ga,Ni,La,Mo,Ag,Hg,Cu,Nb,Zn,Ge,Se,Tl,Cd,Sb,Ba,Y,Ti,Pb,Zr和Sr等元素的含量,并采用方差分析、主成分分析、因子分析等计量学方法进行统计与评价。结果表明：（1）所建立的分析方法线性关系良好,加标回收率高,具有较高的准确度和精密度。（2）35种矿物元素中有33种矿物元素的含量在不同产地间存在显著差异（p＜0.05）。（3）以35种矿物元素的含量为变量,共提取7个主成分,累计方差贡献率达82.75%,主成分得分图显示不同产地艾叶样品的分布相对集中,具备分类和评价的条件。（4）选择前7个因子对艾叶进行综合评价,评价函数为F=0.449 1F₁＋0.118 0F₂＋0.097 2F₃＋0.055 5F₄＋0.042 5F₅+0.034 5F₆+0.030 7F₇,通过计算总因子得分值F可知,河北安国的祁艾与湖北蕲春的蕲艾排在前列,表明从矿物元素角度考虑,以上2个产地的艾叶品质较好。研究建立了不同产地艾叶中矿物元素的准确高效分析方法及评价体系,为艾叶的质量控制及标准建立提供科学依据,也为其他药材的等同性研究提有益参考。     

Synergistic Effect of Photothermal Therapy and Chemotherapy Using Camptothecin‐Conjugated Gold Nanorods

A combinatorial treatment comprising thermal therapy and chemotherapy offers synergistic effects by inducing localized heat to targeted tumor sites and simultaneously delivering anticancer drugs to minimize systemic side effects and enhance the cytotoxic effect. In this study, a novel platform is developed for combining photothermal therapy and chemotherapy using drug‐conjugated gold nanorods (GNRs). Camptothecin (CPT), a model anticancer drug, is chemically conjugated onto GNRs through hydrolytic ester bonding. Upon near‐infrared (NIR) irradiation, localized heat from GNRs in target areas starts to destroy tissues and cells via photothermal therapy, and the elevated temperature accelerates hydrolysis of ester linkage, rapidly releasing drugs for chemotherapy. This combined NIR triggered thermal therapy and chemotherapy with CPT‐functionalized GNRs (CPT‐GNRs) presents a synergistic effect that has high efficacy in in vitro tests, thus providing a robust platform for efficient cancer treatments.     

Poly‐L‐Arginine Grafted Silica Mesoporous Nanoparticles for Enhanced Cellular Uptake and their Application in DNA Delivery and Controlled Drug Release

Mesoporous silica nanoparticles (MSNs), that are capable of delivering gene and drugs to organisms in an effective and selective way have attracted much attention lately for its potential in the treatment of cancer. However, the successful application of MSNs for delivery of plasmid DNA or drugs requires surface modification of the silica with positively charged functional groups so that it binds to the negatively charged nucleic acids and also helps it penetrate through the cell membrane. We report for the first time the synthesis of a hybrid MSN where the cell penetrating cationic polypeptide poly‐L‐arginine synthesized by NCA polymerization is grafted onto the external surface of MSN using click chemistry. These poly‐L‐arginine grafted MSNs show low cytotoxity (85% cell viability at 100 μg/mL MSN concentration) and high cellular uptake by both HeLa and A549 (>90%). The poly‐L‐arginine grafted MSNs were used effectively to deliver mCherry DNA plasmid into cells leading to expression of the protein mCherry inside the cells (transfection efficiency 60%). In contrast, poly‐L‐arginine grafted non‐porous silica nanoparticles were unable to express the protein mCherry inside the cells although their uptake into the cells was as efficient as with poly‐L‐arginine grafted MSNs. We also show preliminary results to demonstrate that these hybrid MSNs can be used as a delivery vehicle for the anticancer drug Doxorubicin towards cancerous cells HeLa and A549. The biocompatibility of poly‐L‐arginine and its cell penetrating ability are expected to make these MSN conjugates very useful carriers for the delivery of genes and drugs into cancer cells.     

Toward ab initio potential energy surface for paclitaxel: a baccatin III conformational study

The ab initio conformational energy profile of baccatin III, the diterpene part of paclitaxel, a natural, taxoid anticancer agent, has been investigated using medium‐size basis sets including an electron correlation method (MP2/DFT). By exploiting the internal coordinates using random search methods, 39 conformers of baccatin III were found. The most stable conformer, competing with its 13‐C rotamers, was shown to have three intramolecular hydrogen bonds of 1, 7 and 13 hydroxyls to the carbonyl oxygen atoms of 2‐benzoate and 10‐ and 4‐acetate ester groups, respectively. The results of the polarizable continuum model (PCM) used to account for the dielectric effect of the environment show that in water, the delicate balances between intramolecular hydrogen bridges and general conformational preferences are conserved, at least in the absence of explicit solvent molecules. Copyright © 2016 John Wiley & Sons, Ltd.     

Molecular properties of selenomaltols: new interesting ligands for bioactive metal complexes

Properties of numerous selenium derivatives of maltol (3‐hydroxy‐2‐methyl‐4H‐pyran‐4‐one), which is an important ligand in medicinal chemistry, were studied. Selenium derivatives were obtained using consecutive in silico replacements of maltol oxygen atoms, which produced three mono‐substituted, three di‐substituted and one tri‐substituted derivatives. The geometry optimisations for these compounds in neutral, anionic and cationic forms were performed at the B1LYP/6‐311++G** level of theory. The aromatic properties of the considered selenium compounds were studied in their heterocyclic rings using several indices of aromaticity: harmonic oscillator model of aromaticity, nucleus independent chemical shift(0), nucleus independent chemical shift(1), aromatic stabilisation energy, H index, para delocalisation index and multicentre index. The methods cover all of the main types of aromaticity indices: geometric, magnetic, energetic and electronic. The calculated data show the identical aromaticity order (cation > neutral molecule > anion) for maltol and its thio and seleno derivatives. The predicted aromaticity levels of selenomaltols were compared with the previously studied maltol and various thiomaltols. Copyright © 2015 John Wiley & Sons, Ltd.     

Structural dynamics of 4‐pyrimidone in lower‐lying excited States

The structural dynamics of 4‐pyrimidone (4PMO) in the A‐ and B‐band absorptions was studied by using the resonance Raman spectroscopy combined with quantum chemical calculations to better understand whether the excited state intramolecular proton‐transfer (ESIPT) reaction occurs in Franck–Condon regions or not. The transition barrier for the ground state proton‐transfer tautomerization reaction between 3(H) (I) and hydroxy (II) was determined to be 165 kJ·mol⁻¹ in vacuum on the basis of the B3LYP/6‐311++G(d,2p) level of theory calculations. Two ultraviolet absorption bands of 4PMO were, respectively, assigned as π_H→π*_L and π_H→π*_L+1 transitions. The vibrational assignments were done on the basis of the Fourier transform (FT)‐Raman and FT‐infrared (IR) measurements, the density‐functional theory computations and the normal mode analysis. The A‐ and B‐band resonance Raman spectra of 4PMO were measured in water, methanol and acetonitrile. The structural dynamics of 4PMO was obtained through the analysis of the resonance Raman intensity pattern. We discuss the similarities in the structural dynamics of 4PMO and 2‐thiopyrimidone (2TPM), and the results were used to correlate to the intramolecular hydrogen‐atom‐transfer process as observed by matrix‐isolation IR experiments for 4PMO. A variety of NH/CH bend modes + C = O stretch mode mark the hydrogen‐detachment‐attachment or ESIPT reaction initiated in Franck–Condon region for 4PMO and 2TPM. Copyright © 2013 John Wiley & Sons, Ltd.     

微波消解ICP-MS法测定根和根茎类生药中11种微量元素

建立了微波消解技术ICP-MS法测定了根及根茎类生药中的铬、锰、镍、钴、铜、锌、砷、硒、钼、镉和铅11种微量元素的方法。对同时适用于两类生药的各微量元素分析的前处理方法进行了研究,从消解体系、酸用量、消解程序等几方面对微波消解条件进行了优化,为同类生药的消解提供了参考。方法检出限为0.001～0.260 μg·g-1,相对标准偏差为0.4%～3.1%,回收率为90%～110%。     

原子吸收光谱法测定不同采收时间栽培与野生羌活药材中微量元素的含量

利用空气-乙炔火焰原子吸收光谱法测定了不同采收时问(5月、6月、7月、8月和9月)的野生与栽培宽叶羌活药材中微量元素Ca,Mg,Fe,Mn,Cu和Zn的含量,应用SPSS16.0分析软件对结果进行统计分析.结果发现:羌活药材含有丰富的微量元素,栽培与野生宽叶羌活药材中微量元素的含量均以Ca元素的含量最高,Cu元素含量最...     

Exploration of small hydroxy‐9,10‐anthraquinones as anthracycline analogues: physicochemical characteristics and DNA binding for comparison

Hydroxy‐9,10‐anthraquinones resemble anthracycline‐based anticancer drugs. By varying the pH of the solution, the proton dissociation constants of 1,2,5,8‐tetrahydroxy‐9,10‐anthraquinone (THAQ) were determined. Interaction of THAQ with calf thymus DNA (ct DNA) was studied by UV–Vis spectroscopy to determine the overall binding constant and site size of interaction. The binding constant values (~10⁴) for THAQ interacting with ct DNA at different pH were an order less than that known for anthracyclines. From knowledge of the overall binding constants at different pH values and the first pK of THAQ, the contribution of each form (neutral and monoanionic) towards overall binding with ct DNA could be obtained under physiological conditions. Hence, knowing the contributions of the neutral and monoanionic forms, it now becomes possible to know the overall binding constant for an interaction of THAQ with ct DNA at any pH. The calculated parameters help in understanding the role of the negative charge on the monoanionic form during interaction and suggests suitable chemical modifications that could prevent the development of such negative charges. This could lead to an increase in binding of THAQ to ct DNA. The study also helps to recognize the importance of sugar units in anthracycline anticancer drugs in DNA interaction. Copyright © 2011 John Wiley & Sons, Ltd.     

Micro‐beam x‐ray fluorescence analysis of individual particles with correction for absorption effects

A method of correction for absorption effects in micro‐beam x‐ray fluorescence analysis is described. A fast, energy‐dispersive, silicon drift detector (SDD) was used to measure the primary x‐ray beam transmitted through the sample. The absorption factors were calculated using the data acquired with the SDD. The possibility of using the coherently, incoherently and multiple scattered primary radiation for determining the mass of individual particles was examined. The proposed methods were validated with the use of NIST K3089 glass micro‐spheres of known composition. Copyright © 2006 John Wiley & Sons, Ltd.     

基于双指标分析法的新疆产罗布麻红外光谱指纹图谱研究

罗布麻作为新疆的特色常用药材,主要用于肝阳眩晕、心悸失眠、浮肿尿少以及高血压、抑郁症的治疗。为保证临床用药安全稳定,常用传统的四大鉴别方法和现代的色谱、波谱技术分析中药材的质量差异。采用傅里叶变换红外光谱（FTIR）法对收集的17份新疆不同产地罗布麻药材进行分析,红外光谱扫描范围为4 000~400 cm-1,二阶导数范围为1 800~600 cm-1,得到图谱后进行图谱解析;采用谱带较密集的指纹区（1 800~400 cm-1）计算红外光谱图的相关系数;然后结合红外光谱吸收峰系统聚类、共有峰率和变异峰率双指标序列分析法对不同产地罗布麻药材的红外指纹图谱进行分类和异同点比较。结果表明,不同产地罗布麻药材红外光谱的峰形、峰位相似,在3 336,2 920,1 443,1 375,1 247,1 103,1 070,833和601 cm-1附近均有吸收,在1 103,1 070和1 656~1 609 cm-1处均存在特征宽强峰。892和717 cm-1处为CO2-₃振动峰,并且仅克拉玛依独山子区药材S4和产地相邻的乌苏市甘家湖保护区药材S5出现此吸收峰,推测与土壤盐碱化程度高有关。除了S5,其余16批罗布麻药材的相似系数均大于0.960,整体相似度较高,说明不同产地罗布麻药材具有一定的相似性。经求导,发现二阶导数光谱的峰形仍具有较大的相似性,但在1 444~1 738和833~1 030 cm-1范围内峰数明显增加。采用SPSS 21.0软件以各药材吸收波数为变量进行聚类分析,S9与S14,S2与S10,S3与S8,S12与S13最先聚为一类;当欧式距离为15时,可将所有药材样品分为四类,即在1 615 cm-1处有吸收峰的药材为一类,在1 646 cm-1处有吸收峰的药材为一类,1 646和1 615 cm-1处均有吸收峰的药材S1为一类,在2 962 cm-1处有吸收的药材S5为一类;当欧式距离为20时,可将药材分为S5和其他药材两大类。双指标序列法结果显示,S9:S14,S2:S10,S3:S8和S12:S13序列共有峰率为100%,罗布麻药材样品总体共有峰率≥61.1%,变异峰率≤53.8%,认为未表现出明显的产地差异性。红外光谱相关系数分析、聚类分析和双指标序列分析结果相互补充和印证,说明该方法可靠有效,可从不同角度分析评价罗布麻药材产地差异,为保证药材质量的稳定可控提供参考。     

On‐line surface enhanced Raman spectroscopic detection in a recyclable Au@SiO2 modified glass capillary

A facile method was developed to fabricate a high sensitive, reproducible and recyclable surface enhanced Raman spectroscopy (SERS) active glass capillary. The Au nanoparticles were synthesized through a seed‐mediated growth approach and then self‐assembled onto the inner wall of glass capillaries. The attached Au nanoparticles were homogeneously coated with thin silica shell by using the silane coupling agent to functionalize the Au surface. By using thiophenol (TP) as SERS probe molecules, the substrate exhibited robust SERS effects. The adsorbed SERS probe molecules could be rapidly and completely removed away by flowing sodium borohydride solution and thus to obtain a refresh Au@SiO₂ film‐coated substrate for the cyclic detection on different species. The on‐line detection of TP and malachite green (MG) with different concentrations was performed in the flowing system. The intensities of SERS signals were dependent on concentrations of the detected molecules. The results indicated that the SERS‐active substrate has potential applications on the on‐line qualitative and quasi‐quantitative analysis. Copyright © 2014 John Wiley & Sons, Ltd.     

Fundamental parameter approach to XRF spectroscopy measurements of arsenic in polyester resin skin phantoms

A fundamental parameter (FP) approach that explicitly incorporates the energy‐broadening response of the detector was developed. The ratio between Kα fluorescence peak area and the sum of coherently and incoherently scattered peak areas was used as an indicator of trace element concentration. The peak ratio was theoretically calculated using the FP method. The energy‐broadening response curve of the Si(Li) detector was estimated by matching the theoretical and experimental values of this ratio. The method was implemented for the analysis of the K‐shell x‐ray fluorescence (K‐XRF) spectra of six polyester resin samples corresponding to six different arsenic concentrations. A ¹⁰⁹Cd radioactive source provided the excitation radiation for spectra acquisition. The predicted detector energy resolution expressed as full width at half‐maximum (FWHM) for Fe Kα fluorescence peak (208 ± 5 eV at 6.4 keV) and As Kα fluorescence peak (222 ± 5 eV at 10.5 keV) were in agreement with the experimental measurements. Copyright © 2008 John Wiley & Sons, Ltd.