Precision Mass Measurement of the Proton Dripline Halo Candidate

We report the first mass measurement of the proton-halo candidate ^{22}Al performed with the low energy beam ion trap facility's 9.4 T Penning trap mass spectrometer at facility for rare isotope beams. This measurement completes the mass information for the lightest remaining proton-dripline nucleus achievable with Penning traps. ^{22}Al has been the subject of recent interest regarding a possible halo structure from the observation of an exceptionally large isospin asymmetry [J. Lee et al., Large isospin asymmetry in Si22/O22 Mirror Gamow-Teller transitions reveals the halo structure of ^{22}Al, Phys. Rev. Lett. 125, 192503 (2020).PRLTAO0031-900710.1103/PhysRevLett.125.192503]. The measured mass excess value of ME=18 092.5(3) keV, corresponding to an exceptionally small proton separation energy of S_{p}=100.4(8) keV, is compatible with the suggested halo structure. Our result agrees well with predictions from sd-shell USD Hamiltonians. While USD Hamiltonians predict deformation in the ^{22}Al ground state with minimal 1s_{1/2} occupation in the proton shell, a particle-plus-rotor model in the continuum suggests that a proton halo could form at large quadrupole deformation. These results emphasize the need for a charge radius measurement to conclusively determine the halo nature.

Making the most of Papua New Guinea's biodiversity: Establishment of an integrated set of programs that link botanical survey with pharmacological assessment in "The Land of the Unexpected"

An integrated and coordinated set of programs has been established to meet ICBG goals in Papua New Guinea (PNG). Here we give an overview of the PNG ICBG and focus on the key elements and major steps taken to establish a program necessary for the pharmacological assessment of botanicals and traditional medicines in PNG and, by extrapolation, in other developing countries.

A new pregnane glycoside and a furostanol glycoside from Digitalis cariensis.

Chemical investigation of the aerial parts of Digitalis cariensis Boiss. ex Jaub. & Spach resulted in the isolation of a new pregnane glycoside, cariensisoside (1) and a furostanol glycoside, uttroside A (2), along with the two known phenylethanoid glycosides, lugrandoside (3) and maxoside (4). On the basis of spectral (UV, IR, NMR, MS) and chemical methods, compounds 1 and 2 were identified as digifologenin-3-O-beta-glucopyranosyl-(1-->4)-beta-oleandropyranoside and 3-O-(beta-lycotetraosyl)-26-O-(beta-glucopyranosyl)-(25R)-22 alpha-methoxy-5-furostane-3 beta,26-diol, respectively.

A novel modified pterin from a Eudistoma species ascidian.

The MeOH extract of an Indonesia Eudistoma sp. ascidian contained 1,3,O(7)-trimethylisoxanthopterin (1), a novel pteridine. The purification of 1 was achieved through flash C(18) chromatography and cyano HPLC. The structure was determined primarily through the use of (1)H-(13)C and (1)H-(15)N HMBC measurements and comparison with data obtained for 1,3,7-trimethylguanine (2).

Flavonoid, iridoid, and lignan glycosides from Putoria calabrica.

From the aerial parts of Putoria calabrica, two new flavonol triglycosides were isolated and their structures were elucidated as quercetin-3-O-[alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranoside]-7-O-beta-D-glucopyranoside (1, calabricoside A) and quercetin-3-O-[4' "-O-caffeoyl-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranoside]-7-O-beta-D-glucopyranoside (2, calabricoside B). Additionally, seven iridoid and three lignan glycosides were isolated and characterized. Radical scavenging activities of all compounds were determined by quantifying their effects on luminol-enhanced chemiluminescence in formyl-methionyl-leucyl-phenylalanine (FMLP) stimulated human polymorphonuclear neutrophils (PMNs). Calabricoside A and B showed strong radical scavenging activity with IC(50) values of 0.25 and 0.3 microM, respectively.

3,7-Dimethylguanine, a new purine from a Philippine sponge Zyzzya fuliginosa.

A new purine 3,7-dimethylguanine (1) has been isolated from the marine sponge Zyzzya fuliginosa, along with the known metabolites, makaluvamines A, C, K (2--4), 4-hydroxyphenylacetic acid (5), methyl ester of 4-hydroxyphenylacetic acid (6), 4-hydroxyphenethyl alcohol (7), L-phenylalanine (8) and L-tryptophan (9). The structure of 3,7-dimethylguanine (1) was elucidated by analysis of 1D and 2D (one- and two-dimensional) NMR [HMQC (heteronuclear multiple quantum coherence), gHMBC (heteronuclear multiple bond connectivity), 1H-15N gHMBC] data, mass spectroscopy data, and by comparison with 3,7-dimethylisoguanine (10).

An iridoid glucoside from Euphrasia pectinata.

A new iridoid glucoside, 5beta,6beta-dihydroxyboschnaloside (1), was isolated from the aerial parts of Euphrasia pectinata. Five known iridoid glucosides, 6beta-hydroxyboschnaloside (2), aucubin, euphroside, plantarenaloside, and geniposidic acid, and two known phenylethanoid glycosides, verbascoside (= acteoside) and leucosceptoside A, were also obtained and characterized. The structure of compound 1 was established by spectroscopic evidence.

Agelasine F from a Philippine Agelas sp. sponge exhibits in vitro antituberculosis activity.

Marine sponge samples were collected in Baler, Aurora, Philippines, and extracts were tested for in vitro antituberculosis activity. An orange Agelas sp. sponge yielded the known compound, agelasine F, which inhibited some drug resistant strains of Mycobacterium tuberculosis in vitro at concentrations as low as 3.13 micrograms/ml. Activity against M. tuberculosis residing within macrophages required concentrations of 13-22 micrograms/ml which was below the IC50 for Vero cells (34 micrograms/ml).

Novel polyketide metabolites from a species of marine fungi.

Fermentation of a marine fungal species obtained from a tissue sample of a marine sponge collected in Indonesia in October 1996, yielded the novel hexaketide compounds iso-cladospolide B (1); seco-patulolide C (2); the 12-membered macrolides, pandangolide 1 (3) and pandangolide 2 (4); and the known terrestrial fungal metabolite, cladospolide B (5).

6-Methoxy-7-methyl-8-oxoguanine, an unusual purine from the ascidian Symplegma rubra.

A new purine derivative, 6-methoxy-7-methyl-8-oxoguanine (1), along with 8-oxoadenine (2) and the human metabolite 3-methylxanthine (3), has been isolated from the ascidian Symplegma rubra collected on the southeastern coastline of Brazil. The structures of the three purines were established by analysis of spectroscopic data.

Trypargine alkaloids from a previously undescribed Eudistoma sp. ascidian.

The MeOH extract of an undescribed Eudistoma sp. ascidian was found to contain the known beta-carboline trypargine (3); the two novel trypargine derivatives trypargimine (4) and 1-carboxytrypargine (5); and 3',5'-dibromo-4'-methoxyphenethylamine (6). The structures of the novel trypargine derivatives were elucidated through the use of mass spectrometry and NMR. The trypargine isolated in this study was found to be nearly racemic in contrast to the previously described isolate which was chiroptically pure. Other previously described compounds detected in the MeOH extract include 4-hydroxyphenylacetamide, tryptamine, 1,3,7-trimethylguanine, and tetrahydropentoxyline (7).

Makaluvamines vary in ability to induce dose-dependent DNA cleavage via topoisomerase II interaction.

The makaluvamines are marine natural products that were originally isolated because of their cytotoxicity in a cell-based mechanism screen. They have significant anti-cancer activity in animal models. There is, however, disagreement in the literature as to whether these compounds target topoisomerase II via a clinically relevant mechanism. This work shows that the makaluvamines can induce dose-dependent DNA cleavage via topoisomerase II. For most of the makaluvamines the levels of cleavage are significantly below those achieved by equimolar concentrations of etoposide. To some extent these results might explain the discrepancies present in the literature.

Naamidine A is an antagonist of the epidermal growth factor receptor and an in vivo active antitumor agent.

The known 2-aminoimidazole alkaloid naamidine A (1) was isolated from a Fijian Leucetta sp. sponge as an inhibitor of the epidermal growth factor (EGF) receptor. The compound exhibited potent ability to inhibit the EGF signaling pathway and is more specific for the EGF-mediated mitogenic response than for the insulin-mediated mitogenic response. Evaluation in an A431 xenograft tumor model in athymic mice indicated that naamidine A exhibited at least 85% growth inhibition at the maximal tolerated dose of 25 mg/kg. Preliminary mechanism of action studies indicate that the alkaloid fails to inhibit the binding of EGF to the receptor and has no effect on the catalytic activity of purified c-src tyrosine kinase.

Three-dimensional solution structure of conotoxin psi-PIIIE, an acetylcholine gated ion channel antagonist.

The three-dimensional structure of conotoxin psi-PIIIE, a 24-amino acid peptide from Conus purpurascens, has been solved using two-dimensional (2D) 1H NMR spectroscopy. Conotoxin psi-PIIIE contains the same disulfide bonding pattern as the mu-conotoxins, which target skeletal muscle sodium channels, but has been shown to antagonize the acetylcholine gated cation channel through a noncompetitive mechanism. Structural information was obtained by the analysis of a series of 2D NOESY spectra as well as measurement of coupling constants from 1D 1H and PE-COSY NMR experiments. Molecular modeling calculations included the use of the distance geometry (DG) algorithm, simulated annealing techniques, and the restrained molecular dynamics method. The resulting structures are considerably similar to the previously published structures for the mu-conotoxins GIIIA and GIIIB, despite the lack of sequence conservation between conotoxin psi-PIIIE and the mu-conotoxins. The structure consists of a series of tight turns, each turn occurring in the position analogous to those of turns described in mu-GIIIA and mu-GIIIB. This suggests the disulfide bonding pattern is able to largely direct the structure of the peptides, creating a stable structural motif which allows extensive sequence substitution of non-cystine residues.

An investigation of a possible role for mitochondrial nuclease in apoptosis.

Since mitochondrial factors have been implicated in apoptosis, experiments were designed to assess whether or not the potent mitochondrial nuclease could be one of these factors. Nuclei isolated by two different methods were found to contain mitochondrial nuclease in masked form. This nuclease was released by treatment with the non-ionic detergent NP-40 and rendered trypsin-sensitive. It was not removed appreciably from the nuclei by washing and sedimentation of the nuclei through a sucrose cushion. Levels of the mitochondrial nuclease were followed during drug-induced apoptosis. Time courses of apoptosis in cultures of HL-60 cells were monitored by flow cytometry of propidium iodide-stained cells and by agarose gel electrophoresis of extracted DNA. Changes in the inner mitochondrial transmembrane potential were monitored by flow cytometry of chloromethyl-X-Rosamine-stained cells. Apoptosis was induced by treatment with either the chemotherapeutic agent etoposide (VP-16 at 10 microM) over an 8 h period or with the anti-rheumatic agent hydroxychloroquine (HCQ at 0.28 mM) over a 24 h period. These two drugs likely act in different pathways of apoptosis. VP-16 caused loss of the mitochondrial transmembrane potential 1.0-1.5 h before apoptosis was detected. On the other hand, treatment with HCQ caused these processes to occur in parallel possibly indicating that the mitochondrial changes are secondary events. No losses of masked mitochondrial nuclease were detected with either drug treatment during the course of apoptosis. HL-60 mitochondrial DNA was also not degraded during apoptosis induced by either agent. These observations likely explain why the mitochondrial DNA is not degraded and make it unlikely that mitochondrial nuclease plays any role in vivo in chromatin DNA fragmentation.

Plakinidine D, a new pyrroloacridine alkaloid from two ascidians of the genus Didemnum.

A previously undescribed red Didemnum sp. collected in Indonesia contained a novel pyrroloacridine, plakinidine D (4), along with the known compounds 3,5-diiodo-4-methoxyphenethylamine (5) and ascididemin (6), both of which had previously been isolated from ascidians of the genus Didemnum. Plakinidine D (4) and 3,5-diiodo-4-methoxyphenethylamine (5) were also isolated from Didemnum rubeum from the Republic of Palau. Interestingly, a collection of D. rubeum from Indonesia did not contain plakinidine D (4), but instead contained 3,5-diiodo-4-methoxyphenethylamine (5) and ascididemin (6). The structure of plakinidine D (4) was elucidated by analysis of its spectral data. Plakinidine D (4) is closely related to plakinidines A-C (1-3), previously isolated from the sponge Plakortis sp.

Isolation and characterization of 1,3-dimethylisoguanine from the Bermudian sponge Amphimedon viridis.

The new compound 1,3-dimethylisoguanine has been isolated and characterized from the Bermudian sponge Amphimedon viridis. Chemical conversion of the natural product to theophylline and 2D NMR methods were used to determine the position of the methyl groups on the purine ring. Analysis of the mass spectral fragmentation pattern allowed assignment of the purine ring as isoguanine.