Direct analysis of camptothecin from Nothapodytes nimmoniana by desorption electrospray ionization mass spectrometry (DESI-MS)

Desorption electrospray ionization was employed for fast and direct ambient detection of the anti-tumor drug, camptothecin, and its derivative, 9-methoxycamptothecin in Nothapodytes nimmoniana. Different parts of the plant such as leaves, stems and bark were examined. The ion intensities suggest that the concentration in bark is higher than that in the leaves and stems. The method does not require any sample preparation or preseparation. The identity of the alkaloids was further confirmed by tandem mass spectrometry

Ambient ionization mass spectrometry imaging of rohitukine, a chromone anti-cancer alkaloid, during seed development in Dysoxylum binectariferum Hook.f (Meliaceae)

Rohitukine, a chromone alkaloid, possesses anti-inflammatory, anti-cancer and immuno-modulatory properties. It has been reported from four species, belonging to the families, Meliaceae and Rubiaceae. Stem bark of Dysoxylum binectariferum (Meliaceae) accumulates the highest amount of rohitukine (3–7% by dry weight). In this study, we examine the spatial and temporal distribution of rohitukine and related compounds during various stages of seed development in D. binectariferum using desorption electrospray ionization mass spectrometry imaging (DESI MSI). Rohitukine (m/z 306.2) accumulation increased from early seed development to seed maturity stage. The spatial distribution of rohitukine was largely restricted to the cotyledonary tissue followed by the embryo and least in the seed coat. Besides rohitukine, rohitukine acet ate (m/z 348.2) and glycosylated rohitukine (m/z 468.2) were also detected, both through mass fragmentation and exact mass analysis through Orbitrap mass spectrometry. These results indicate a dynamic pattern of chromane alkaloid accumulation through seed development in D. binectariferum

Desorption Electrospray Ionization (DESI) Mass Spectrometric Imaging of the Distribution of Rohitukine in the Seedling of Dysoxylum binectariferum Hook. F.

Ambient ionization mass spectrometric imaging of all parts of the seedling of Dysoxylum binectariferum Hook. f (Meliaceae) was performed to reconstruct the molecular distribution of rohitukine (Rh) and related compounds. The species accumulates Rh, a prominent chromone alkaloid, in its seeds, fruits, and stem bark. Rh possesses anti-inflammatory, anti-cancer, and immuno-modulatory properties. Desorption electrospray ionization mass spectrometry imaging (DESI MSI) and electrospray ionization (ESI) tandem mass spectrometry (MS/MS) analysis detected Rh as well as its glycosylated, acetylated, oxidized, and methoxylated analogues. Rh was predominantly distributed in the main roots, collar region of the stem, and young leaves. In the stem and roots, Rh was primarily restricted to the cortex region. The identities of the metabolites were assigned based on both the fragmentation patterns and exact mass analyses. We discuss these results, with specific reference to the possible pathways of Rh biosynthesis and translocation during seedling development in D. binectariferum

Early Detection of Biofouling on Water Purification Membranes by Ambient Ionization Mass Spectrometry Imaging

By direct analysis of water purification membranes using ambient ionization mass spectrometry, an attempt has been made to understand the molecular signatures of bacterial fouling. Membrane based purification methods are used extensively in water treatment, and a major challenge for them is biofouling. The buildup of microbes and their extracellular polymeric matrix clog the purification membranes and reduce their efficiency. To understand the early stages of bacterial fouling on water purification membranes, we have used desorption electrospray ionization mass spectrometry (DESI MS), where ion formation occurs in ambient conditions and the ionization event is surface sensitive. Biosurfactants at the air–water interface generated by microorganisms as a result of quorum sensing, influence the water–membrane interface and are important for the bacterial attachment. We show that these biosurfactants produced by bacteria can be indicator molecular species signifying initiation of biofilms on membrane surfaces, demonstrated by specific DESI MS signatures. In <i>Pseudomonas aeruginosa</i>, one of the best studied models for biofilm formation, this process is mediated by rhamnolipids forewarning bacterial fouling. Species dependent variation of such molecules can be used for the precise identification of the microorganisms, as revealed by studies on <i>P. aeroginosa</i> (ATCC 25619). The production of biosurfactants is tightly regulated at the transcriptional level by the quorum-sensing (QS) response. Thus, secretion of these extracellular molecules across the membrane surface allows rapid screening of the biofilm community. We show that, the ambient ionization mass spectrometry can detect certain toxic heavy metals present in water, using surfactant–metal complexes as analytes. We believe that such studies conducted on membranes in various input water streams will help design suitable membrane processes specific to the input streams

Early Detection of Biofouling on Water Purification Membranes by Ambient Ionization Mass Spectrometry Imaging

By direct analysis of water purification membranes using ambient ionization mass spectrometry, an attempt has been made to understand the molecular signatures of bacterial fouling. Membrane based purification methods are used extensively in water treatment, and a major challenge for them is biofouling. The buildup of microbes and their extracellular polymeric matrix clog the purification membranes and reduce their efficiency. To understand the early stages of bacterial fouling on water purification membranes, we have used desorption electrospray ionization mass spectrometry (DESI MS), where ion formation occurs in ambient conditions and the ionization event is surface sensitive. Biosurfactants at the air–water interface generated by microorganisms as a result of quorum sensing, influence the water–membrane interface and are important for the bacterial attachment. We show that these biosurfactants produced by bacteria can be indicator molecular species signifying initiation of biofilms on membrane surfaces, demonstrated by specific DESI MS signatures. In <i>Pseudomonas aeruginosa</i>, one of the best studied models for biofilm formation, this process is mediated by rhamnolipids forewarning bacterial fouling. Species dependent variation of such molecules can be used for the precise identification of the microorganisms, as revealed by studies on <i>P. aeroginosa</i> (ATCC 25619). The production of biosurfactants is tightly regulated at the transcriptional level by the quorum-sensing (QS) response. Thus, secretion of these extracellular molecules across the membrane surface allows rapid screening of the biofilm community. We show that, the ambient ionization mass spectrometry can detect certain toxic heavy metals present in water, using surfactant–metal complexes as analytes. We believe that such studies conducted on membranes in various input water streams will help design suitable membrane processes specific to the input streams

Tissue imprint imaging by desorption electrospray ionization mass spectrometry

Cross-sections of Myristica malabarica (Lam) seed and mouse brain tissue were imprinted on such ordinary surfaces as printer paper and TLC plates, and successfully imaged by desorption electrospray ionization mass spectrometry (DESI-MS) at 250 µm resolution. Chemical images representing the distribution of the alkaloid malabaricone C in the seed substructures and individual lipids in the substructures of the brain were obtained. Practical implications include analysis of irregular or soft materials, easy recording, transportation and storage of the latent image, and posterior analysis of the samples by different techniques without the requirement of addition of matrices or use of specific types of surfaces

DESI MS images showing the distribution of Rh and other related compounds in the imprinted leaf of a 10 months old seedling of <i>D</i>. <i>binectariferum</i>.

<p>Scale bar corresponds to 5 mm applies to all the images.</p

Nucleolin-aptamer therapy in retinoblastoma: molecular changes and mass spectrometry–based imaging

Retinoblastoma (RB) is an intraocular childhood tumor which, if left untreated, leads to blindness and mortality. Nucleolin (NCL) protein which is differentially expressed on the tumor cell surface, binds ligands and regulates carcinogenesis and angiogenesis. We found that NCL is over expressed in RB tumor tissues and cell lines compared to normal retina. We studied the effect of nucleolin-aptamer (NCL-APT) to reduce proliferation in RB tumor cells. Aptamer treatment on the RB cell lines (Y79 and WERI-Rb1) led to significant inhibition of cell proliferation. Locked nucleic acid (LNA) modified NCL-APT administered subcutaneously (s.c.) near tumor or intraperitoneally (i.p.) in Y79 xenografted nude mice resulted in 26 and 65% of tumor growth inhibition, respectively. Downregulation of inhibitor of apoptosis proteins, tumor miRNA-18a, altered serum cytokines, and serum miRNA-18a levels were observed upon NCL-APT treatment. Desorption electrospray ionization mass spectrometry (DESI MS)-based imaging of cell lines and tumor tissues revealed changes in phosphatidylcholines levels upon treatment. Thus, our study provides proof of concept illustrating NCL-APT-based targeted therapeutic strategy and use of DESI MS-based lipid imaging in monitoring therapeutic responses in RB

Schematic representation of possible biosynthetic pathway of Rh in <i>D</i>. <i>binectariferum</i>.

<p>Schematic representation of possible biosynthetic pathway of Rh in <i>D</i>. <i>binectariferum</i>.</p

Direct Observation of the Formation Pathway of [Mo₁₃₂] Keplerates

The formation pathway of a closed spherical cluster [Mo₁₃₂], starting from a library of building blocks of molybdate anions, has been reported. Electrospray ionization mass spectrometry, Raman spectroscopy, and theoretical studies describe the formation of such a complex cluster from a reduced and acidified aqueous solution of molybdate. Understanding the emergence of such an enormous spherical model cluster may lead to the design of new clusters in the future. Formation of such a highly symmetric cluster is principally controlled by charge balance and the emergence of more symmetric structures at the expense of less symmetric ones