Applications of Chemometrics for Characterization of Macromolecules

The possibilities of employing methods of chemometrics in order to characterize macromolecules are described. The review has been limited to chemometric methods concerning multivariate data analysis. Principal component analysis (PCA) has shown to be very useful for pattern recognition problems arising from chromatographic and spectroscopic data. An example of using a classification technique, SIMCA (Soft Independent Modelling of Class Analogy), as a product control method is presented. The suitability of Partial Least Squares (PLS) for relating data of different natures, e.g. chemical data with biological data, is discussed. Moreover, examples ranging from spectroscopic determinations to QSAR (Quantitative Structure Activity Relationships) are illustrated.     

Representation of electron backscatter diffraction data

Abstract

Current methods of data representation for electron backscatter diffraction (EBSD) measurements are reviewed. Obtaining diffraction data from microstructures using EBSD has become a relatively straightforward procedure, and EBSD software packages are used to represent these data as qualitative statistics in the form of ideal orientations, pole figures, inverse pole figures, Euler space, and Rodrigues–Frank space. Quantitative statistics in the form of secondary computations allow full microtextural analysis. Additionally, the power of EBSD is demonstrated through positional information representation. Through experimental examples, the conversion of EBSD data to statistical information to facilitate interpretation of results is demonstrated.

MST/3678     

Characterization of phyto-nanoparticles from Ficus krishnae for their antibacterial and anticancer activities

Background: Ovarian cancer is deadliest of fifth leading cause of death in women worldwide. This is due to advanced-stage disease rate associated with the development of chemoresistance. Hence, the current study emphasizes the process of synthesis of silver nanoparticles (AgNPs) from green chemistry method. Ficus krishnae is a perennial plant, native to India, used in folklore medicine to treat various diseases.

Objective: For the development of reliable, ecofriendly, less expensive process for the synthesis of AgNPs against bacterial and ovarian cancer.

Methodology: The synthesis of silver nanoparticles from stem bark of Ficus krishnae was carried out. The synthesized nanoparticles are subjected by UV-Vis spectrophotometer, scanning electron microscopy (SEM), X-ray diffraction (XRD) analysis and FTIR analysis. The antibacterial efficacy also determined by disc diffusion method, MIC, CFU and growth curve. In vitro cytotoxicity effect of aqueous extract and AgFK nanoparticle in ovarian cancer cell line by MTT assay was performed.

Results: The formation of AgNPs was confirmed by UV-VIS spectroscopic absorbance shown that peak at 435?nm. XRD photograph has indicated the face-centered cubic structure of the synthesized AgNPs. SEM study demonstrated that the size from 160 to 260?nm with interparticle distance, whereas shape is spherical. The particle size were ranging from 15 to 28?nm determined by XRD pattern. The antibacterial and cytotoxicity activity of this nanoparticle has showed a potential activity when compared with standards.

Conclusion: The present study confirms that the biosynthesized AgNPs from Ficus krishnae stem bark extract have a great affiance as antibacterial and anticancer agent.     

Glycerolipids as Selective Thrombin Inhibitors from the Fungus Stereum Hirsutum

ABSTRACT

A dry extract of Stereum hirsutum exhibited a significant inhibitory activity on thrombin (34%). A bioassay oriented fractionation of the extract of Stereum hirsutum has led to the isolation of two active fractions. On the basis of spectroscopic data, chemical reactions, and GC-MS analysis, complex mixtures of diacylglycerophospholipids (DAGPs) and diacylglycerols (DGs) have been isolated and identified. Docking studies suggest that some isolated compounds could bind to the thrombin active site in a similar manner as previously reported phosphonate thrombin inhibitors.     

Building a drug development database: challenges in reliable data availability

Abstract

Context: Policy and legislative efforts to improve the biomedical innovation process must rely on a detailed and thorough analysis of drug development and industry output.

Objective: As part of our efforts to build a publicly-available database on the characteristics of drug development, we present work undertaken to test methods for compiling data from public sources. These initial steps are designed to explore challenges in data extraction, completeness and reliability. Specifically, filing dates for Investigational New Drugs (IND) applications with the U.S. Food and Drug Administration (FDA) were chosen as the initial objective data element to be collected.

Materials and methods: FDA’s Drugs@FDA database and the Federal Register (FR) were used to collect IND dates for the 587 New Molecular Entities (NMEs) approved between 1994 and 2014. When available, the following data were captured: approval date, IND number, IND date and source of information.

Results: At least one IND date was available for 445 (75.8%) of the 587 NMEs. The Drugs@FDA database provided IND dates for 303 (51.6%) NMEs and the FR contributed with 297 (50.6%) IND dates. Out of the 445 NMEs for which an IND date was obtained, 274 (61.6%) had more than one date reported.

Discussion: Key finding of this paper is a considerable inconsistency in reliably available or reported data elements, in this particular case, IND application filing dates as assembled from publicly-available sources.

Conclusion: Our team will continue to focus on finding ways to collect relevant information to measure impact of drug innovation.     

Interaction pattern and in vitro,in vivo release behavior of simvastatin-loaded chitosan nanoformulation

Abstract

Objective and methods: This study predicted the nature of chitosan interactions and effects of this interaction on drug release mechanism in simvastatin-loaded chitosan nanoformulation using molecular docking, spectroscopic and thermal analysis.

Significance: This work explains in depth the molecular mechanism of simvastatin and chitosan bond formation in nanoformulation.

Results: The effective encapsulation and sustain release properties of chitosan were indicated by increase in melting endotherm of simvastatin. Intermolecular hydrogen bond between third hydroxyl group pyranone ring of simvastatin and amino group of chitosan represented the stability of active lactone moiety that was not cleaved during formulation which is prerequisite for biological activity. UV–vis spectroscopic characterization, shift in infrared vibration wavenumber of simvastatin and chitosan, ligand titration, 1HNMR and 13C-NMR analyses confirmed this interaction pattern. The pharmacokinetic evaluation in mouse model revealed the sustain release property of nanoformulation.

Conclusion: Thus formation of intermolecular hydrogen bond in nanoformulation contributed to modified physicochemical properties and improved in vivo performance of simvastatin.     

Biophysical Approaches to the Pharmaceutical Development of Proteins

Abstract

The complexity of protein pharmaceuticals necessitates a multifaceted approach to their characterization, stabilization, and development. The combined use of spectroscopic, hydrodynamic, chromatographic and thermodynamic methods to evaluate various levels of macromolecular structure is described. Near future developments in our ability to evaluate proteins at high structural resolution are also considered.     

On the Analysis of Dissolution Data

Abstract

Dissolution profiles for solid dose forms represent several observations over time on an experimental unit such as a tablet or capsule. The pharmaceutical scientist is interested in a (statistical) comparison of these profiles under a variety of conditions relating to formulation characteristics, and lot-to-lot and brand-to-brand variation.

This paper discusses the analysis of dissolution profiles using an analysis of variance approach. la particular, the profiles are tested for differences in level and shape. The latter characteristic is potentially important with respect to learning about differences in the dissolution mechanism.

An approximate F test is discussed with the possibility of an arbitrary covariance matrix in mind, and alternative conservative analysis methods are presented.

Results from the analysis of variance of typical dissolution data show several important features. First, the analysis does not rely on curve fitting procedures and the data are used in their native form or as a simple transform. Second, the data can be analyzed using the fraction dissolved and/or the time for a particular fraction to dissolve, e.g., t_50%, as the variable of interest. Finally, the analysis is capable of showing differences between profiles where a realistic variation from profile-to-profile exists.     

Supramolecular Complexes between Fullerene [60]- and [70], and resorcinarene

Abstract

New complexes 2 and 3 between [60]- and [70] fullerenes with resorcinarene 1 were prepared and characterized by spectroscopic methods. Resorcinarene 1 was studied in solution by NMR and in the solid state by CP-MAS NMR and X-ray diffraction. The macrocycle 1 can guest one [60]- or [70] fullerene molecule in its structure. For the complexes 2 and 3, π-π, CH-π and n-π interactions were observed by ¹³C CP-MAS and FTIR analysis data.     

1, 5-Bis (2-hydroxyacetophenone)thiocarbohydrazone: A novel colorimetric and fluorescent dual-mode chemosensor for the recognition of fluoride

1,5-Bis (2-hydroxyacetophenone)thiocarbohydrazone (H₄L) has been synthesized and characterized by means of spectroscopic and single crystal X-ray diffraction methods. Interactions of the H₄L with a variety of anions were investigated using a combination of UV–visible and fluorescence spectroscopic methods in a biological competing solvent DMSO. The H₄L has a high degree of selectivity for fluoride over other anions. ¹H NMR titration experiments indicate that a deprotonation process is involved in the chemo sensing process.     

Spatial analysis of environmental impacts of highway projects with special emphasis on mountainous area: an overview

Abstract

Mountains are progressively being invaded by highways for development and defence purposes. Environmental impact assessment (EIA) of highway projects in mountainous areas creates a challenging environment for data collection and impact prediction. Geographic information systems (GIS)-based EIA, using appropriate spatial analysis methods can sufficiently reduce the challenges created by mountain environments. The present study includes a review of articles, including research papers, government reports and EIA reports cutting across the inter-disciplinary nature of the topic. The paper identifies the spatial analysis methods, models and salient features of conducting GIS-based EIA of highway projects in mountainous areas. It is observed that spatial analysis of impacts of highway projects on the environmental attributes, especially air, noise, water and socio-economy in mountainous areas are largely unexplored.     

Toward methods for supporting the anticipation-feedback loop in user interface design

Recent research has compared different usability evaluation methods with respect to their effectiveness and efficiency. The paper analyses the impact of different usability evaluation methods on design problem-solving processes of individual designers and evaluators. It is proposed that usability evaluation methods have to be divided into two categories according to their fundamentally different way of supporting the design for usability: (1) guideline-based methods and (2) methods based on the mental generation of scenarios and anticipation of user goals. We present data from an experimental study that shows that these two types of methods entail differences in the perspective-taking processes. Furthermore, the results indicate that the methods have a differential impact on the general problem-solving strategy, i.e. whether to use a top-down, breadth-first or a depth-first approach. Possible implications for the development of techniques that support the design of usable systems are discussed.     

Stilbene-based liquid crystalline and photocrosslinkable polynaphthylphosphate esters

A series of liquid crystalline and photocrosslinkable polymers were synthesized from 4,4′-bis(m-hydroxyalkyloxy)stilbene (m = 2, 4, 6, 8, 10) with naphthylphosphorodichloridate. The synthesized polymers were characterized by spectroscopic techniques. Thermogravimetric analysis revealed that the polymers were stable between 283 and 341 °C, then underwent two-stage decomposition, and char yield increased with decreasing spacer length. DSC and HOPM analysis disclosed that the polymers III–V (m = 6, 8, 10) exhibited LC phases wherein flexible methylene spacer separates mesogenic alignment and reduces overall rigidity of polymers, while polymers I and II are unable to show LC phase. The photolysis was studied by UV–visible and fluorescence spectroscopy. The rate of photocrosslinking increases with increase in methylene chain. The fluorescence property decreased with successive UV irradiation in the polymers.     

Analysis of Nasal Solutions Containing Phenylephrine Hydrochloride and Pheniramine Maleate by High Performance Liquid Chromatography on a Cyclodextrin Bonded Stationary Phase and Diode Array Spectrophotometry

Abstract

Methods based on high performance liquid chromatography (HPLC) and diode array spectroscopy for the analysis of phenylephrine hydrochloride and pheniramine maleate in nasal spray solutions have been developed. No interferences from excipients in the formulation occur with either method of analysis which should he applicable to uniformity of content testing. There was no statistical difference (P<0.01) in the analyses of the two drugs by either method. The novelty of the HPLC method lies in the use of a cyclodextrin bonded stationary phase which allows simultaneous analysis of phenylephrine and pheniramine. These two drugs could not be analysed by reversed phase HPLC since pheniramine did not elute from the column under conditions which produced adequate retention of phenylephrine. The advantage of diode array spectroscopy lies in its speed of analysis. For analysis by HPLC, the accuracies were 100.3% for phenylephrine and 100.8% for pheniramine, the system precision (% RSDs) was 0.48% for phenylephrine and 0.23% for pheniramine and the method precision was 1.82% for phenylephrine and 1.63% for pheniramine. Various methods of manipulating the raw spectroscopic data were investigated. For analysis at two wavelengths, determinations at 262 nm and 273 nm gave the best results. For analysis over a range of wavelengths, 255 to 266 nm was preferred for determination using zero or first order derivatives. A range of 273 to 290 nm gave better results for determinations using second order derivatives. The accuracies and precisions varied with the method of data manipulation and the same method did not give optimal values of these parameters for both drugs. The best compromise for the analysis of pheniramine and phenylephrine was obtained with zero order spectra obtained over the range 255 to 262 nm. Under these conditions, the accuracies were 102.9% for phenylephrine and 99.7% for pheniramine, the system precisions were 0.12% for phenylephrine and 0.31% for pheniramine and the method precisions were 1.44% for phenylephrine and 1.45% for pheniramine.     

Conversion of infrared radiation into visible in ZBLAN glass with three-component doping by rare-earth elements

Experimental results are presented that lead to the conclusion that new laser systems and elements of fiber-optic communication lines can in principle be made on the basis of the material studied here, which have new spectroscopic characteristics. The effect studied in this paper is the following: an increase in the luminescence efficiency with frequency upconversion for three-element doping; this is a novel finding and has no analog. Pis’ma Zh. Tekh. Fiz. 23, 51–57 (January 26, 1997)     

MacroPCA: An All-in-One PCA Method Allowing for Missing Values as Well as Cellwise and Rowwise Outliers

Abstract

Multivariate data are typically represented by a rectangular matrix (table) in which the rows are the objects (cases) and the columns are the variables (measurements). When there are many variables one often reduces the dimension by principal component analysis (PCA), which in its basic form is not robust to outliers. Much research has focused on handling rowwise outliers, that is, rows that deviate from the majority of the rows in the data (e.g., they might belong to a different population). In recent years also cellwise outliers are receiving attention. These are suspicious cells (entries) that can occur anywhere in the table. Even a relatively small proportion of outlying cells can contaminate over half the rows, which causes rowwise robust methods to break down. In this article, a new PCA method is constructed which combines the strengths of two existing robust methods to be robust against both cellwise and rowwise outliers. At the same time, the algorithm can cope with missing values. As of yet it is the only PCA method that can deal with all three problems simultaneously. Its name MacroPCA stands for PCA allowing for Missingness And Cellwise & Rowwise Outliers. Several simulations and real datasets illustrate its robustness. New residual maps are introduced, which help to determine which variables are responsible for the outlying behavior. The method is well-suited for online process control.     

Review Grain and subgrain characterisation by electron backscatter diffraction

The application of automated Electron Backscatter Diffraction (EBSD) in the scanning electron microscope, to the quantitative analysis of grain and subgrain structures is discussed and compared with conventional methods of quantitative metallography. It is shown that the technique has reached a state of maturity such that linescans and maps can routinely be obtained and analysed using commercially available equipment and that EBSD in a Field Emission SEM (FEGSEM) allows quantitative analysis of grain/subgrains as small as 0.2 m. EBSD can often give more accurate measurements of grain and subgrain size than conventional imaging methods, often in comparable times. Subgrain/cell measurements may be made more easily than in the TEM although the limited angular resolution of EBSD may be problematic in some cases. Additional information available from EBSD and not from conventional microscopy, gives a new dimension to quantitative metallography. Texture and its correlation with grain or subgrain size, shape and position are readily measured. Boundary misorientations, which are readily obtainable from EBSD, enable the distribution of boundary types to be determined and CSL boundaries can be identified and measured. The spatial distribution of Stored Energy in a sample and the amount of Recrystallization may also be measured by EBSD methods.     

On truncated poisson distribution for determining mean number of defectives in pharmaceutical products

Abstract

The Poisson distribution plays a dominant role in the determination of the mean value of a distribution of the number of defective units (e.g. tablets, capsules) per sample, based on several samples of same size. If, however, the data emanates from samples with at least one defective unit in each sample, involving the absence of the zero-defective category, then the formula of the Poisson distribution as well as of the mean number of defective units are no longer tenable. In this presentation, appropriate formula for the Poisson distribution, called the truncated Poisson distribution, and for the mean, θ, are developed. The maximum likelihood method of estimation of the parameter θ by employing numerical (iterative) analysis methods is depicted, in detail. The procedure for conducting the chi-square test of goodness of fit of the experimental data to the truncated Poisson distribution is demonstrated. The results of the analyses of two recent experiments based on the methods described above are presented and appropriately interpreted.     

The Use of Simple Relationships between Wavefront Aberration and Wavelength to Approximate the Polychromatic Optical Transfer Functions of 8 to 12 µm Thermal Imaging Lenses

Abstract

Two methods are described which can be used to predict polychromatic optical transfer functions (OTFs) of thermal imaging lenses to good accuracy from only one finite ray trace. These methods offer some saving in calculation time and could be used to predict polychromatic OTFs from monochromatic test data provided suitable paraxial data and spectral details are available.     

Carbonization and oxidation of metal–organic frameworks based on 1,4-naphthalene dicarboxylates

Abstract

Three new isostructural metal–organic frameworks (MOFs), [V(OH)(NDC)] (1), [Cr(OH)(NDC)] (2), and [Ga(OH)(NDC)] (3) have been synthesized hydrothermally using 1,4-naphthalene dicarboxylate (NDC) as the linker. These MOFs (1, 2 and 3) have been used as a template for the synthesis of metal-oxide-inserted nanoporous carbon materials. The newly synthesized MOFs and the resulting porous carbon hybrid functional materials have been characterized using powder x-ray diffraction, scanning electron microscopy, transmission electron microscopy, and energy dispersive x-ray spectroscopic analysis. Results show that compounds 2 and 3 form their respective metal oxide nanoparticles on the surface of the carbon materials during carbonization at 800 °C. The gas sorption properties of the new MOFs and their corresponding carbon frameworks have been reported.