A new potential ligand for paramagnetic complexes acting as a receptor-specific MRI contrast agen... more A new potential ligand for paramagnetic complexes acting as a receptor-specific MRI contrast agent was investigated by means of one-and two-dimensional NMR spectroscopy and mass spectrometry. A complete assignment of the structure is reported.
Journal of Photochemistry and Photobiology A: Chemistry, 1997
... isomers of some merocyanines: a 1 N and theoretical CS INFO study of the structures and elect... more ... isomers of some merocyanines: a 1 N and theoretical CS INFO study of the structures and electronic spectra Ivan Baraldi a, Stefano Ghelli a, Zhanna A. Krasnaya b, Fabio Momicchioli a, Aleksandr S. Tatikolov ', Davide ... [7] D. Frackowiak, M. Niedbalska, M. Romanowski and 1 ...
Asymmetric benzimidazolo carbo, di- and tricarbocyanines form ion pairs of the solvent-separated ... more Asymmetric benzimidazolo carbo, di- and tricarbocyanines form ion pairs of the solvent-separated and contact types with different counterions in tetrahydrofuran, toluene and toluene–nitrile mixtures. The dissociation constants of the ion pairs in tetrahydrofuran, evaluated from conductivity data, do not depend on the length of the polymethine chain and show only a small decrease with decreasing counterion size. The absorption and
Abstract The 1 H NMR spectra of the labile photoisomers of 3,3′-diethyloxa- and 3,3′-diethylthiac... more Abstract The 1 H NMR spectra of the labile photoisomers of 3,3′-diethyloxa- and 3,3′-diethylthiacarbocyanines have been recorded for the first time. Analysis of these spectra leads to the identification of the photoisomer of the first dye as a mono-cis form obtained by twisting about the central polymethine bond, and to the suggestion that the photoisomerization of the second dye takes place around the external polymethine bond. These assignments are shown to be generally consistent with the results of earlier experimental and theoretical studies of the ground- and excited-state behaviour of these compounds.
Thymidylate synthase (TS, ThyA) catalyzes the reductive methylation of 2&... more Thymidylate synthase (TS, ThyA) catalyzes the reductive methylation of 2'-deoxyuridine 5'-monophosphate to 2'-deoxythymidine 5'-monophosphate, an essential precursor for DNA synthesis. A specific inhibition of this enzyme induces bacterial cell death. As a second round lead optimization design, new 1,2-naphthalein derivatives have been synthesized and tested against a TS-based biolibrary, including human thymidylate synthase (hTS). Docking studies have been performed to rationalize the experimentally observed affinity profiles of 1,2-naphthalein compounds toward Lactobacillus casei TS and hTS. The best TS inhibitors have been tested against a number of clinical isolates of Gram-positive-resistant bacterial strains. Compound 3,3-bis(3,5-dibromo-4-hydroxyphenyl)-1H,3H-naphtho[1,2-c]furan-1-one (5) showed significant antibacterial activity, no in vitro toxicity, and dose-response effects against Staphylococcus epidermidis (MIC=0.5-2.5 microg/mL) clinical isolate strains, which are resistant to at least 17 of the best known antibacterial agents, including vancomycin. So far this compound can be regarded as a leading antibacterial agent.
A new set of phthalein derivatives stemming from the lead compound, phenolphthalein, were designe... more A new set of phthalein derivatives stemming from the lead compound, phenolphthalein, were designed to specifically complement structural features of a bacterial form of thymidylate synthase (Lactobacillus casei, LcTS) versus the human TS (hTS) enzyme. The new compounds were screened for their activity and their specificity against TS enzymes from different species, namely, L. casei (LcTS), Pneumocystis carinii (PcTS), Cryptococcus neoformans (CnTS), and human thymidylate synthase (hTS). Apparent inhibition constants (K i) for all the compounds against LcTS were determined, and inhibition factors (IF, ratio between the initial rates of the enzymatic reaction in the presence and absence of each inhibitor) against each of the four TS species were measured. A strong correlation was found between the two activity parameters, IF and K i , and therefore the simpler IF was used as a screening factor in order to accelerate biological evaluation. Compounds 5b, 5c, 5ba, and 6bc showed substantial inhibition of LcTS while remaining largely inactive against hTS, illustrating for the first time remarkable species specificity among TSs. Due to sequence homology between the enzymes, several compounds also showed high activity and specificity for CnTS. In particular, 3-hydroxy-3-(3-chloro-4hydroxyphenyl)-6-nitro-1H,3H-naphtho[1,8-c,d]pyran-1-one (6bc) showed an IF < 0.04 for CnTS (K i) 0.45 µM) while remaining inactive in the hTS assay at the maximum solubility concentration of the compound (200 µM). In cell culture assays most of the compounds were found to be noncytotoxic to human cell lines but were cytotoxic against several species of Grampositive bacteria. These results are consistent with the enzymatic assays. Intriguingly, several compounds also had selective activity against Cr. neoformans in cell culture assay. In general, the most active and selective compounds against the Gram-positive bacteria were those designed and found in the enzyme assay to be specific for LcTS versus hTS. The original lead compound was least selective against most of the cell lines tested. To our knowledge these compounds are the first TS inhibitors selective for bacterial TS with respect to hTS.
H R-M AS N M R spectroscopy was utilized for the characterization of three cosmetic emul sions. T... more H R-M AS N M R spectroscopy was utilized for the characterization of three cosmetic emul sions. The emulsions had the same chemical composition and were prepared in the same way except the homogenization step. Magic angle spinning (M A S) of the emulsions was applied to improve signal resolution by eliminating susceptibility changes as well as residual dipolar interactions within the sample. Spin-lattice relaxation times (Tj) were determined according to the inversion recovery technique in the temperature range of-10 °C to 40 °C to find out phase changes of the sample ingredients. 'H and 13C N M R signals of the individual compo nents were assigned by use of different ID and 2D N M R experiments. The HR-M AS N M R technique offers many possibilities to further investigate samples between the liquid and the solid state.
The up-take of Gd(III) complexes of BOPTA, DTPA, DOTA, EDTP, HPDO3A, and DOTP in HRBC has been ev... more The up-take of Gd(III) complexes of BOPTA, DTPA, DOTA, EDTP, HPDO3A, and DOTP in HRBC has been evaluated by measuring the lanthanide induced shift (LIS) produced by the corresponding dysprosium complexes (DC) on the MAS-NMR resonances of water protons and free sodium ions. These complexes are important in their use as MRI contrast agents (MRI-CA) in diagnostics. 1H and 23Na MAS-NMR spectra of HRBC suspension, collected at 9.395T, show only one signal due to extra- and intra-cellular water (or sodium). In MAS spectra, the presence of DC in a cellular compartment produces the LIS of only the nuclei (water proton or sodium) in that cellular compartment and this LIS can be related to the DC concentrations (by the experimental curves of LIS vs. DC concentrations) collected in the physiological solution. To obtain correct results about LIS, the use of MAS technique is mandatory, because it guarantees the only the nuclei staying in the same cellular compartment where the LC is present show the LIS. In all the cases considered, the addition of the DC to HRBC (100% hematocrit) produced a shift of only the extra-cellular water (or sodium) signal and the gradient of concentration (GC) between extra- and intra-cellular compartments resulted greater than 100:1, when calculated by means of sodium signals. These high values of GC are direct proofs that none of the tested dysprosium complexes crosses the HRBC membrane. Since the DC are iso-structural to the gadolinium complexes the corresponding gadolinium ones (MRI-CA) do not cross the HRBC membrane and, consequently, they are not up-taken in HRBC. The GC values calculated by means of water proton signals resulted much lower than those obtained by sodium signals. This proves that the choice of the isotope is a crucial step in order to use this method in the best way. In fact, GC value depends on the lowest detectable LIS which, in turn, depends on the nature of the LC (lanthanide complex) and the observed isotopes.
ABSTRACT The chloro substituted 3,3-di-(4′-hydroxyphenyl)-1-oxo-1H,3H-naphtho[1,8-cd]pyran was sy... more ABSTRACT The chloro substituted 3,3-di-(4′-hydroxyphenyl)-1-oxo-1H,3H-naphtho[1,8-cd]pyran was synthesized in a 40/60 mixture of C6 or C7 substituted isomers, respectively. The two isomers were separated by hplc. The X-ray crystal structure of the mixture was obtained. Both the mixture and the single isomers were tested against Lactobacillus Casei thymidylate synthase. The X-ray analysis clearly revealed co-crystallization of the two isomeric species. The apparent Ki of the mixture was 0.8 muM, while those of the C6 and C7 substituted isomers were 0.42 and 0.52 muM, respectively, thus showing that the position of the chlorine in the naphthalene ring was not critical for enzymatic activity.
Journal of the American Oil Chemists' Society, 2000
Analytical measurements and proton nuclear magnetic resonance (1H NMR) spectra of phenolic extrac... more Analytical measurements and proton nuclear magnetic resonance (1H NMR) spectra of phenolic extracts were performed on a set of italian extra‐virgin olive oils from different cultivars and geographical locations of Apulia region. Multivariate statistical analysis (principal component analysis, hierarchical clustering analysis, and discriminant analysis) was applied separately to analytical and NMR data. Analytical parameters, in particular fatty acid compositions, permit the discrimination of olive variety, while 1H NMR data of phenolic extracts permit a classification according to the geographical origin of the samples.
Journal of the American Oil Chemists' Society, 2004
Characterization of the lipid fraction of raw cow and buffalo milk samples, collected in differen... more Characterization of the lipid fraction of raw cow and buffalo milk samples, collected in different breeding areas in Apulia, a region of southern Italy, were performed by means of 1H NMR. The aim of this work was to establish whether FA composition data obtained by 1H NMR can be used in the differentiation of buffalo and cow milk samples according to species. A complete assignment of the signals present in the spectrum was attempted by COSY, heteronuclear coherence spectra. Quantification of FA was carried out by inserting the integrals of particular peaks in suitable calculations. Multivariate statistical analysis, conducted on the results of the quantification, permitted buffalo and cow milks to be distinguished.
... of these model com-pounds prompted us to investigate the solid-state structure of a series of... more ... of these model com-pounds prompted us to investigate the solid-state structure of a series of polyoxyethylenated dode-canols and their ... References 1. Rosh M (1971) Tenside Detergents 8:302 2. Schneider G, Gulden W (1984) Proc of World Surfactants Congress 4:305 3 ...
C-H activation of benzylic methyl groups has been realized catalytically under mild conditions th... more C-H activation of benzylic methyl groups has been realized catalytically under mild conditions through intramolecular reaction on a palladium complex. † Electronic supplementary information (ESI) available: selected spectroscopic data for compounds 6, 7, 15 and 16. See http://www.rsc.org/ suppdata/cc/b0/b005182i/ Scheme 1 Scheme 2 Reagents and conditions: i, 10% mol Pd(OAc) 2 , KOAc, DMF, N 2 , 18 h, 105 °C, 91% conversion. Scheme 3 Proposed mechanism for the palladium-catalyzed synthesis of 6 and 7. Solvent or reagent molecules as ligands are omitted for simplicity.
A new potential ligand for paramagnetic complexes acting as a receptor-specific MRI contrast agen... more A new potential ligand for paramagnetic complexes acting as a receptor-specific MRI contrast agent was investigated by means of one-and two-dimensional NMR spectroscopy and mass spectrometry. A complete assignment of the structure is reported.
Journal of Photochemistry and Photobiology A: Chemistry, 1997
... isomers of some merocyanines: a 1 N and theoretical CS INFO study of the structures and elect... more ... isomers of some merocyanines: a 1 N and theoretical CS INFO study of the structures and electronic spectra Ivan Baraldi a, Stefano Ghelli a, Zhanna A. Krasnaya b, Fabio Momicchioli a, Aleksandr S. Tatikolov &#x27;, Davide ... [7] D. Frackowiak, M. Niedbalska, M. Romanowski and 1 ...
Asymmetric benzimidazolo carbo, di- and tricarbocyanines form ion pairs of the solvent-separated ... more Asymmetric benzimidazolo carbo, di- and tricarbocyanines form ion pairs of the solvent-separated and contact types with different counterions in tetrahydrofuran, toluene and toluene–nitrile mixtures. The dissociation constants of the ion pairs in tetrahydrofuran, evaluated from conductivity data, do not depend on the length of the polymethine chain and show only a small decrease with decreasing counterion size. The absorption and
Abstract The 1 H NMR spectra of the labile photoisomers of 3,3′-diethyloxa- and 3,3′-diethylthiac... more Abstract The 1 H NMR spectra of the labile photoisomers of 3,3′-diethyloxa- and 3,3′-diethylthiacarbocyanines have been recorded for the first time. Analysis of these spectra leads to the identification of the photoisomer of the first dye as a mono-cis form obtained by twisting about the central polymethine bond, and to the suggestion that the photoisomerization of the second dye takes place around the external polymethine bond. These assignments are shown to be generally consistent with the results of earlier experimental and theoretical studies of the ground- and excited-state behaviour of these compounds.
Thymidylate synthase (TS, ThyA) catalyzes the reductive methylation of 2&amp;amp;amp;amp;amp;... more Thymidylate synthase (TS, ThyA) catalyzes the reductive methylation of 2&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;-deoxyuridine 5&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;-monophosphate to 2&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;-deoxythymidine 5&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;-monophosphate, an essential precursor for DNA synthesis. A specific inhibition of this enzyme induces bacterial cell death. As a second round lead optimization design, new 1,2-naphthalein derivatives have been synthesized and tested against a TS-based biolibrary, including human thymidylate synthase (hTS). Docking studies have been performed to rationalize the experimentally observed affinity profiles of 1,2-naphthalein compounds toward Lactobacillus casei TS and hTS. The best TS inhibitors have been tested against a number of clinical isolates of Gram-positive-resistant bacterial strains. Compound 3,3-bis(3,5-dibromo-4-hydroxyphenyl)-1H,3H-naphtho[1,2-c]furan-1-one (5) showed significant antibacterial activity, no in vitro toxicity, and dose-response effects against Staphylococcus epidermidis (MIC=0.5-2.5 microg/mL) clinical isolate strains, which are resistant to at least 17 of the best known antibacterial agents, including vancomycin. So far this compound can be regarded as a leading antibacterial agent.
A new set of phthalein derivatives stemming from the lead compound, phenolphthalein, were designe... more A new set of phthalein derivatives stemming from the lead compound, phenolphthalein, were designed to specifically complement structural features of a bacterial form of thymidylate synthase (Lactobacillus casei, LcTS) versus the human TS (hTS) enzyme. The new compounds were screened for their activity and their specificity against TS enzymes from different species, namely, L. casei (LcTS), Pneumocystis carinii (PcTS), Cryptococcus neoformans (CnTS), and human thymidylate synthase (hTS). Apparent inhibition constants (K i) for all the compounds against LcTS were determined, and inhibition factors (IF, ratio between the initial rates of the enzymatic reaction in the presence and absence of each inhibitor) against each of the four TS species were measured. A strong correlation was found between the two activity parameters, IF and K i , and therefore the simpler IF was used as a screening factor in order to accelerate biological evaluation. Compounds 5b, 5c, 5ba, and 6bc showed substantial inhibition of LcTS while remaining largely inactive against hTS, illustrating for the first time remarkable species specificity among TSs. Due to sequence homology between the enzymes, several compounds also showed high activity and specificity for CnTS. In particular, 3-hydroxy-3-(3-chloro-4hydroxyphenyl)-6-nitro-1H,3H-naphtho[1,8-c,d]pyran-1-one (6bc) showed an IF < 0.04 for CnTS (K i) 0.45 µM) while remaining inactive in the hTS assay at the maximum solubility concentration of the compound (200 µM). In cell culture assays most of the compounds were found to be noncytotoxic to human cell lines but were cytotoxic against several species of Grampositive bacteria. These results are consistent with the enzymatic assays. Intriguingly, several compounds also had selective activity against Cr. neoformans in cell culture assay. In general, the most active and selective compounds against the Gram-positive bacteria were those designed and found in the enzyme assay to be specific for LcTS versus hTS. The original lead compound was least selective against most of the cell lines tested. To our knowledge these compounds are the first TS inhibitors selective for bacterial TS with respect to hTS.
H R-M AS N M R spectroscopy was utilized for the characterization of three cosmetic emul sions. T... more H R-M AS N M R spectroscopy was utilized for the characterization of three cosmetic emul sions. The emulsions had the same chemical composition and were prepared in the same way except the homogenization step. Magic angle spinning (M A S) of the emulsions was applied to improve signal resolution by eliminating susceptibility changes as well as residual dipolar interactions within the sample. Spin-lattice relaxation times (Tj) were determined according to the inversion recovery technique in the temperature range of-10 °C to 40 °C to find out phase changes of the sample ingredients. 'H and 13C N M R signals of the individual compo nents were assigned by use of different ID and 2D N M R experiments. The HR-M AS N M R technique offers many possibilities to further investigate samples between the liquid and the solid state.
The up-take of Gd(III) complexes of BOPTA, DTPA, DOTA, EDTP, HPDO3A, and DOTP in HRBC has been ev... more The up-take of Gd(III) complexes of BOPTA, DTPA, DOTA, EDTP, HPDO3A, and DOTP in HRBC has been evaluated by measuring the lanthanide induced shift (LIS) produced by the corresponding dysprosium complexes (DC) on the MAS-NMR resonances of water protons and free sodium ions. These complexes are important in their use as MRI contrast agents (MRI-CA) in diagnostics. 1H and 23Na MAS-NMR spectra of HRBC suspension, collected at 9.395T, show only one signal due to extra- and intra-cellular water (or sodium). In MAS spectra, the presence of DC in a cellular compartment produces the LIS of only the nuclei (water proton or sodium) in that cellular compartment and this LIS can be related to the DC concentrations (by the experimental curves of LIS vs. DC concentrations) collected in the physiological solution. To obtain correct results about LIS, the use of MAS technique is mandatory, because it guarantees the only the nuclei staying in the same cellular compartment where the LC is present show the LIS. In all the cases considered, the addition of the DC to HRBC (100% hematocrit) produced a shift of only the extra-cellular water (or sodium) signal and the gradient of concentration (GC) between extra- and intra-cellular compartments resulted greater than 100:1, when calculated by means of sodium signals. These high values of GC are direct proofs that none of the tested dysprosium complexes crosses the HRBC membrane. Since the DC are iso-structural to the gadolinium complexes the corresponding gadolinium ones (MRI-CA) do not cross the HRBC membrane and, consequently, they are not up-taken in HRBC. The GC values calculated by means of water proton signals resulted much lower than those obtained by sodium signals. This proves that the choice of the isotope is a crucial step in order to use this method in the best way. In fact, GC value depends on the lowest detectable LIS which, in turn, depends on the nature of the LC (lanthanide complex) and the observed isotopes.
ABSTRACT The chloro substituted 3,3-di-(4′-hydroxyphenyl)-1-oxo-1H,3H-naphtho[1,8-cd]pyran was sy... more ABSTRACT The chloro substituted 3,3-di-(4′-hydroxyphenyl)-1-oxo-1H,3H-naphtho[1,8-cd]pyran was synthesized in a 40/60 mixture of C6 or C7 substituted isomers, respectively. The two isomers were separated by hplc. The X-ray crystal structure of the mixture was obtained. Both the mixture and the single isomers were tested against Lactobacillus Casei thymidylate synthase. The X-ray analysis clearly revealed co-crystallization of the two isomeric species. The apparent Ki of the mixture was 0.8 muM, while those of the C6 and C7 substituted isomers were 0.42 and 0.52 muM, respectively, thus showing that the position of the chlorine in the naphthalene ring was not critical for enzymatic activity.
Journal of the American Oil Chemists' Society, 2000
Analytical measurements and proton nuclear magnetic resonance (1H NMR) spectra of phenolic extrac... more Analytical measurements and proton nuclear magnetic resonance (1H NMR) spectra of phenolic extracts were performed on a set of italian extra‐virgin olive oils from different cultivars and geographical locations of Apulia region. Multivariate statistical analysis (principal component analysis, hierarchical clustering analysis, and discriminant analysis) was applied separately to analytical and NMR data. Analytical parameters, in particular fatty acid compositions, permit the discrimination of olive variety, while 1H NMR data of phenolic extracts permit a classification according to the geographical origin of the samples.
Journal of the American Oil Chemists' Society, 2004
Characterization of the lipid fraction of raw cow and buffalo milk samples, collected in differen... more Characterization of the lipid fraction of raw cow and buffalo milk samples, collected in different breeding areas in Apulia, a region of southern Italy, were performed by means of 1H NMR. The aim of this work was to establish whether FA composition data obtained by 1H NMR can be used in the differentiation of buffalo and cow milk samples according to species. A complete assignment of the signals present in the spectrum was attempted by COSY, heteronuclear coherence spectra. Quantification of FA was carried out by inserting the integrals of particular peaks in suitable calculations. Multivariate statistical analysis, conducted on the results of the quantification, permitted buffalo and cow milks to be distinguished.
... of these model com-pounds prompted us to investigate the solid-state structure of a series of... more ... of these model com-pounds prompted us to investigate the solid-state structure of a series of polyoxyethylenated dode-canols and their ... References 1. Rosh M (1971) Tenside Detergents 8:302 2. Schneider G, Gulden W (1984) Proc of World Surfactants Congress 4:305 3 ...
C-H activation of benzylic methyl groups has been realized catalytically under mild conditions th... more C-H activation of benzylic methyl groups has been realized catalytically under mild conditions through intramolecular reaction on a palladium complex. † Electronic supplementary information (ESI) available: selected spectroscopic data for compounds 6, 7, 15 and 16. See http://www.rsc.org/ suppdata/cc/b0/b005182i/ Scheme 1 Scheme 2 Reagents and conditions: i, 10% mol Pd(OAc) 2 , KOAc, DMF, N 2 , 18 h, 105 °C, 91% conversion. Scheme 3 Proposed mechanism for the palladium-catalyzed synthesis of 6 and 7. Solvent or reagent molecules as ligands are omitted for simplicity.
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Papers by Stefano Ghelli