Tomasz Ruman

Gold nanoparticle-enhanced target (AuNPET) as universal solution for laser desorption/ionization mass spectrometry analysis and imaging of low molecular weight compounds.

Preparation is described of a durable surface of cationic gold nanoparticles (AuNPs), covering commercial and custom-made MALDI targets, along with characterization of the nanoparticle surface properties and examples of the use in MS analyses and MS imaging (IMS) of low molecular weight (LMW) organic compounds. Tested compounds include nucleosides, saccharides, amino acids, glycosides, and nucleic bases for MS measurements, as well as over one hundred endogenous compounds in imaging experiment. The nanoparticles covering target plate were enriched in sodium in order to promote sodium-adduct formation. The new surface allows fast analysis, high sensitivity of detection and high mass determination accuracy. Example of application of new Au nanoparticle-enhanced target for fast and simple MS imaging of a fingerprint is also presented.

Molecular Sieves in Medicine

During the last few decades microporous and mesoporous materials have been considered for medical use due to biological properties and stability in biological environment. Zeolites have been investigated as drug carriers, and as adjuvants in anticancer therapy, dietetic supplements or antimicrobial agents. This review gives a brief overview of the major aspects of molecular sieves applications in medicine.

Novel monoisotopic 109AgNPET for laser desorption/ionization mass spectrometry.

Preparation is described of the surface of the first monoisotopic cationic (109)Ag nanoparticles (AgNPs), covering commercial and modified MALDI targets, along with examples of the use in MS analyses of various low-molecular-weight (LMW) organic compounds, including alkaloids, saccharides, amino acids, nucleosides, nucleic bases, and other organics. The new targets, compared to those covered by naturally occurring silver, allow analyte detection with higher sensitivity, mass accuracy, and resolution. Moreover, monoisotopic triatomic silver cations (109)Ag(3)(+) appear to be applicable for analyte cationization.

Thiophosphorylation of free amino acids and enzyme protein by thiophosphoramidate ions

In search of an activity-preserving protein thiophosphorylation method, with thymidylate synthase recombinant protein used as a substrate, potassium thiophosphoramidate and diammonium thiophosphoramidate salts in Tris- and ammonium carbonate based buffer solutions were employed, proving to serve as a non-destructive environment. Using potassium phosphoramidate or diammonium thiophosphoramidate, a series of phosphorylated and thiophosphorylated amino acid derivatives was prepared, helping, together with computational (using density functional theory, DFT) estimation of (31)P NMR chemical shifts, to assign thiophosphorylated protein NMR resonances and prove the presence of thiophosphorylated lysine, serine and histidine moieties. Methods useful for prediction of (31)P NMR chemical shifts of thiophosphorylated amino acid moieties, and thiophosphates in general, are also presented. The preliminary results obtained from trypsin digestion of enzyme shows peak at m/z 1825.805 which is in perfect agreement with the simulated isotopic pattern distributions for monothiophosphate of TVQQQVHLNQDEYK where thiophosphate moiety is attached to histidine (His(26)) or lysine (Lys(33)) side-chain.

Electron capture dissociation mass spectrometric analysis of lysine-phosphorylated peptides

Phosphorylation of proteins is an essential signalling mechanism in eukaryotic and prokaryotic cells. Although N-phosphorylation of basic amino acid is known for its importance in biological systems, it is still poorly explored in terms of products and mechanisms. In the present study, two MS fragmentation methods, ECD (electron-capture dissociation) and CID (collision-induced dissociation), were tested as tools for analysis of N-phosphorylation of three model peptides, RKRSRAE, RKRARKE and PLSRTLSVAAKK. The peptides were phosphorylated by reaction with monopotassium phosphoramidate. The results were confirmed by 1H NMR and 31P NMR studies. The ECD method was found useful for the localization of phosphorylation sites in unstable lysine-phosphorylated peptides. Its main advantage is a significant reduction of the neutral losses related to the phosphoramidate moiety. Moreover, the results indicate that the ECD–MS may be useful for analysis of regioselectivity of the N-phosphorylation reaction. Stabilities of the obtained lysine-phosphorylated peptides under various conditions were also tested.

Complexes of heteroscorpionate trispyrazolylborate anionic ligands. Part III. X-ray crystallographic and NMR studies on cobalt(II) complexes with tris(pyrazolyl)borate anionic ligands obtained from 3,5-di-methylpyrazole and 3(5)-methyl,5(3)-phenylpyrazole

Abstract Condensation of 2 equiv. of 5(3)-methyl,3(5)-phenylpyrazole and 1 equiv. of 3,5-di-methylpyrazole with NaBH4 resulted in the formation of sodium [hydrobis(3-phenyl,5-methylpyrazolyl)(3,5-di-methylpyrazolyl)borate]. The ligand was converted into the pentacoordinate [HB(3,5-di-Mepz)(3-Ph,5-Mepz)2]Co(NCS)(THF)·THF complex for which the molecular structure was determined by the X-ray crystallographic method. The geometry of the ligand in the cobalt(II) complex was compared with that of the homoscorpionate ligand in [HB(3-Ph,5-Mepz)3]Co(NCS)(THF)·0.5THF on the basis of X-ray structural data. The condition for the thermal conversion of the ligands in the studied Tp′Co(NCS) was established. The heating of the mentioned complexes at 428 K in propylbenzene resulted in a borotropic shift of 3-phenyl,5-methylpyrazolyl moieties resulting in the formation of new heteroscorpionates: the chiral [HB(3,5-di-Mepz)(3-Ph,5-Mepz)(3-Me,5-Phpz)]Co(NCS) and [HB(3-Me,5-Phpz)2(3-Ph,5-Mepz)]Co(NCS), which were characterized in solution by 1H NMR spectroscopy.

Surface-transfer mass spectrometry imaging on a monoisotopic silver nanoparticle enhanced target.

A new method for both high-resolution laser desorption/ionization mass spectrometry and mass spectrometry imaging is described. The method could be considered as matrix-less because no additional matrix is needed for MS measurements and also because of surface-assisted laser desorption/ionization due to the nanoparticle-rich surface. The standard matrix-assisted laser desorption/ionization target containing unique monoisotopic cationic (109)Ag nanoparticles ((109)AgNPs) was used for high-resolution mass spectrometry imaging of fingermarks and also plant flower and plant stem cross sections with high mass accuracy. The methodology presented in this work allowed visualization of two drugs--anti-inflammatory ibuprofen and anticancer 5-fluorouracil--along with many other compounds found on the finger. Moreover, visualization of herbicide localization inside of the plant stem is also shown. The simple inorganic ions ionized by silver nanoparticles were also found and may be used for their localization in biological material. In addition, the methodology presented here does not require freezing of species or slice-making equipment.

Anionic Poly(pyrazolyl)borate Ligands Obtained from 3,5-Dimethylpyrazole and 3,5-Diphenylpyrazole and Their Cobalt(II) Complexes − X-ray Crystallographic and1H NMR Studies

Synthesis of poly(pyrazolyl)borate anionic ligands composed of 3,5-dimethyl- and 3,5-diphenylpyrazoles and their bis(ligand) high-spin cobalt(II) complexes are described. The molecular structures of [dihydrobis(3,5-diphenylpyrazolyl)borato][hydrobis(3,5-dimethylpyrazolyl)(3,5-diphenylpyrazolyl)borato]cobalt(II) and bis[dihydro(3,5-dimethylpyrazolyl)(3,5-diphenylpyrazolyl)borato]cobalt(II) complexes were established by X-ray crystallography. The cobalt center is hexacoordinate in the former with five Co−N2(pyrazolyl) bonds and short Co−H [attached to the boron atom of bis(pyrazolyl)borate] bond (2.03 A), whereas a distorted tetrahedral geometry was found for the latter due to four Co−N2(pyrazolyl) bonds. Additionally, the pentacoordinate homoscorpionate [tris(3,5-diphenylpyrazolyl)borato]cobalt(II) nitrate side product was obtained from the reaction and characterized structurally. It contains a κ3-coordinated Tp′ ligand and a κ2-bound nitrate anion.

Complexes of heteroscorpionate trispyrazolylborate ligands. Part VI. Carboxylate induced conversion of mono-ligand Tp′M(L) into bis-ligand Tp′2M complexes (M=Co(II) and Cu(II))

Abstract A series of homoleptic complexes of hexacoordinate cobalt(II) and copper(II) complexes with 3,5-disubstituted homo- and heteroscorpionate tris(pyrazolyl)borate anionic ligands (Tp′) were synthesized, i.e. bis[hydrotris(3-phenyl,5-methylpyrazol-1-yl)borato]cobalt(II), bis[hydrobis(3-phenyl,5-methylpyrazol-1-yl)(3-methyl,5-phenylpyrazol-1-yl)borato]cobalt(II) and bis[hydrobis(3-phenyl,5-methylpyrazol-1-yl)(3-methyl,5-phenylpyrazol-1-yl)borato]copper(II) and their structures were elucidated crystallographically. The complexes were also formed spontaneously during attempted metathesis of the corresponding Tp′M(NCS) complexes into Tp′M(OOCCH(OH)CH3) complexes. In the case of the analogous conversion applied for the thiocyanato [hydrobis(3-phenyl,5-methylpyrazol-1-yl)(3,5-dimethylpyrazol-1-yl)boratocobalt(II) complex with sodium carboxylates (lactate, pyruvate and 2-hydroxybutyrate), the cross-transfer of pyrazolyl residues between starting anionic ligands was observed resulting in formation of bis-ligand homo- and heteroleptic Tp′CoTp″ complexes, where Tp′, Tp″ were tris(pyrazolyl)borates composed of n 3(5)-phenyl,5(3)-methylpyrazolyl and (3−n) 3,5-dimethylpyrazolyl residues (n=0–3) identified by mass spectrometry. Metathesis of thiocyanate in thiocyanato hydrotris(3-phenyl,5-methylpyrazol-1-yl)boratocobalt(II) into pyruvate led to the isolation of stable the pyruvato hydrotris(3-phenyl,5-methylpyrazol-1-yl)boratocobalt(II) complex, the structure of which was determined crystallographically. The Tp′ ligands are η3 coordinated to metal ions in every case, whereas the pyruvate anion is coordinated through carboxylate and carbonyl oxygen atoms to the cobalt center. Two rotational isomers distinguishable by 1H NMR spectroscopy for the hexacoordinate bis[hydrobis(3-phenyl,5-methylpyrazol-1-yl)(3-methyl,5-phenylpyrazol-1-yl)borato]cobalt(II) complex were detected in solution.

Complexes of heteroscorpionate trispyrazolylborate anionic ligands: Part II. The X-ray crystallographic and 1H NMR studies on thiocyanato[hydrobis(3-phenylpyrazolyl)(3,5-di-tert-butylpyrazolyl)borato]cobalt(II) and thiocyanato[hydrobis(3-phenyl,5-methylpyrazolyl)(3-methyl,5-phenylylpyrazolyl)borato]cobalt(II) complexes

Abstract Synthesis of two heteroscorpionate tris(pyrazolyl)borate anionic ligands (Tp′) was described; the sterically demanding [hydrobis(3-phenylpyrazolyl)(3,5-di-tert-butylpyrazolyl)borate]− obtained by condensation of KBH4 with 3-phenylpyrazole and 3,5-di-tert-butylpyrazole and [hydrobis(3-phenyl,5-methylpyrazolyl)(3-methyl, 5-phenylylpyrazolyl)borate]− formed in similar reaction between NaBH4 and 3(5)-methyl,5(3)-phenylpyrazole. The ligands were converted into tetracoordinate [HB(3,5-di-tBupz)(3-Phpz)2]Co(NCS) and pentacoordinate [HB(3-Me,5-Phpz)(3-Ph,5-Mepz)2]Co(NCS)(THF)·THF complexes, which molecular structures were determined by X-ray crystallographic method. The reactivity of high-spin cobalt(II) complexes was studied by the 1H NMR spectroscopy in solution. The reactive [HB(3-Me,5-Phpz)(3-Ph,5-Mepz)2]Co(NCS) complex readily underwent conversions into pentacoordinate [HB(3-Me,5-Phpz)(3-Ph,5-Mepz)2]Co(OOCCH(OH)CH3) and hexacoordinate [HB(3-Me,5-Phpz)(3-Ph,5-Mepz)2]Co[HB(pz)3] complexes.