Paolo Scrimin - Academia.edu (original) (raw)

Papers by Paolo Scrimin

Chemistry – A European Journal

Journal of the American Chemical Society

The activity of many enzymes is regulated by associative processes. To model this mechanism, we r... more The activity of many enzymes is regulated by associative processes. To model this mechanism, we report here that the conformation of an unstructured bimetallic Zn(II) complex can be controlled by its inclusion in the cavity of a γ-cyclodextrin. This results in the formation of a catalytic bimetallic site for the hydrolytic cleavage of the RNA model substrate HPNP, whose reactivity is 30-fold larger with respect to the unstructured complex. Competitive inhibition with 1-adamantanecarboxylate displaces the metal complex from the cyclodextrin decreasing the reactivity.

ACS Catalysis

Recent studies have shown that gold nanoparticles (AuNPs) functionalized with Zn(II) complexes ca... more Recent studies have shown that gold nanoparticles (AuNPs) functionalized with Zn(II) complexes can cleave phosphate esters and nucleic acids. Remarkably, such synthetic nanonucleases appear to catalyze metal (Zn)-aided hydrolytic reactions of nucleic acids similar to metallonuclease enzymes. To clarify the reaction mechanism of these nanocatalysts, here we have comparatively analyzed two nanonucleases with a >10-fold difference in the catalytic efficiency for the hydrolysis of the 2hydroxypropyl-4-nitrophenylphosphate (HPNP, a typical RNA model substrate). We have used microsecond-long atomistic simulations, integrated with NMR experiments, to investigate the structure and dynamics of the outer coating monolayer of these nanoparticles, either alone or in complex with HPNP, in solution. We show that the most efficient one is characterized by coating ligands that promote a well-organized monolayer structure, with the formation of solvated bimetallic catalytic sites. Importantly, we have found that these nanoparticles can mimic two-metal-ion enzymes for nucleic acid processing, with Zn ions that promote HPNP binding at the reaction center. Thus, the two-metal-ion-aided hydrolytic strategy of such nanonucleases helps in explaining their catalytic efficiency for substrate hydrolysis, in accordance with the experimental evidence. These mechanistic insights reinforce the parallelism between such functionalized AuNPs and proteins toward the rational design of more efficient catalysts.

Nanomaterials

The biotin–avidin interaction is used as a binding tool for the conjugation of biomolecules for m... more The biotin–avidin interaction is used as a binding tool for the conjugation of biomolecules for more diverse applications; these include nanoparticle conjugation. Despite this, a thorough investigation on the different aggregates that may result from the interaction of biotinylated nanoparticles (gold nanoparticles, AuNPs, in this work) with avidin has not been carried out so far. In this paper, we address this problem and show the type of aggregates formed under thermodynamic and kinetic control by varying the biotinylated AuNP/avidin ratio and the order of addition of the two partners. The analysis was performed by also addressing the amount of protein able to interact with the AuNPs surface and is fully supported by the TEM images collected for the different samples and the shift of the surface plasmon resonance band. We show that the percentage of saturation depends on the size of the nanoparticles, and larger nanoparticles (19 nm in diameter) manage to accommodate a relatively ...

Nanomaterials

Drug-loaded, PEGylated, organic-modified silica (ORMOSIL) nanoparticles prepared by microemulsion... more Drug-loaded, PEGylated, organic-modified silica (ORMOSIL) nanoparticles prepared by microemulsion condensation of vinyltriethoxysilane (VTES) were investigated as potential nanovectors for cancer therapy. To target cancer stem cells, anti-CD44v6 antibody and hyaluronic acid (HA) were conjugated to amine-functionalized PEGylated ORMOSIL nanoparticles through thiol-maleimide and amide coupling chemistries, respectively. Specific binding and uptake of conjugated nanoparticles were studied on cells overexpressing the CD44v6 receptor. Cytotoxicity was subsequently evaluated in the same cells after the uptake of the nanoparticles. Internalization of nanocarriers loaded with the anticancer drug 3N-cyclopropylmethyl-7-phenyl-pyrrolo- quinolinone (MG2477) into cells resulted in a substantial increase of the cytotoxicity with respect to the free formulation. Targeting with anti-CD44v6 antibodies or HA yielded nanoparticles with similar effectiveness, in their optimized formulation.

European Journal of Organic Chemistry

Nanomaterials

The challenge to obtain plasmonic nanosystems absorbing light in the near infrared is always open... more The challenge to obtain plasmonic nanosystems absorbing light in the near infrared is always open because of the interest that such systems pose in applications such as nanotherapy or nanodiagnostics. Here we describe the synthesis in an aqueous solution devoid of any surfactant of Au-nanowires of controlled length and reasonably narrow dimensional distribution starting from Au-nanoparticles by taking advantage of the properties of glucosamine phosphate under aerobic conditions and substoichiometric nanoparticle passivation. Oxygen is required to enable the process where glucosamine phosphate is oxidized to glucosaminic acid phosphate and H2O2 is produced. The process leading to the nanosystems comprises nanoparticles growth, their aggregation into necklace-like aggregates, and final fusion into nanowires. The fusion requires the consumption of H2O2. The nanowires can be passivated with an organic thiol, lyophilized, and resuspended in water without losing their dimensional and opti...

Biopolymers, Jan 12, 2018

Gold nanoparticles are known to aggregate in the presence of proper multifunctional compounds. Fo... more Gold nanoparticles are known to aggregate in the presence of proper multifunctional compounds. For those larger than 3 nm, the process can be followed with the naked eye because the surface plasmon absorption band of the particles shifts to longer wavelengths and the solution color changes from red to blue. To exploit this property, we have used amino acids and peptides as crosslinking agents in ethanol at low µM concentrations. In the case of amino acids, we report a straightforward protocol for their colorimetric identification. We also report that the presence of precise secondary structure and conformational constraints in oligopeptides, directly influence their crosslinking ability. A discussion on the nature of the interactions that induce these phenomena is also reported.

Organic Preparations and Procedures International, 1991

Separ Sci Technol, 1982

The degradation with nitric acid of kerosene-type diluents of TBP in the reprocessing of nuclear ... more The degradation with nitric acid of kerosene-type diluents of TBP in the reprocessing of nuclear fuel leads to the formation of primary nitroalkanes. These, under acid conditions, may hydrolyze to hydroxamic acids, HA, which are well-known complex-ing agents of many metal ions, including Zr. The formation of very stable HA-Zr complexes has been proposed as a rationale for the retention of Zr in the diluents. However, the results of this study carried out in a model system, the acid-catalyzed conversion of 1-nitropropane to propanhydroxamic acid, and the subsequent hydrolysis to carboxylic acid and hydroxylamine—easily extensible to the actual reprocessing processes—indicate that in these systems the equilibrium concentration of hydroxamic acids attainable is too low (10 to 10 M) to account for the “zirconium retention” phenomenon.

Http Dx Doi Org 10 1080 15257770008033049, Sep 24, 2006

The hydrolytic activity of the 1,3,5-triaminocyclohexane derivatives TACH, TACI and TMCA complexe... more The hydrolytic activity of the 1,3,5-triaminocyclohexane derivatives TACH, TACI and TMCA complexed to Zn(II) and Cu(II) towards a model phosphoric ester and plasmid DNA has been evaluated by means of spectroscopic and gel-electrophoresis techniques. At conditions close to physiological, a prominent cleavage effect mediated by the nature of the ligand and metal ion was generally observed. TACI complexes are the most active in relaxing supercoiled DNA, the effect being explained by the affinity of the hydroxylated ligand for the nucleic acid. As indicated by the dependence of cleavage efficiency upon pH, Zn(II)-complexes act by a purely hydrolytic mechanism. In the case of Cu(II)-complexes, although hydrolysis should be prominent, involvement of an oxidative pathway cannot be completely ruled out.

Journal of the Chemical Society, Perkin Transactions 2, 1986

... or Zinc( 11) Roberto Fornasier, Daria Milani, Paolo Scrimin,' and Um... more ... or Zinc( 11) Roberto Fornasier, Daria Milani, Paolo Scrimin,' and Umberto Tonellato Centro 'Meccanismi di Reazioni Organiche del C. NR, lstituto di Chimica Organica, Universita di Pado va, 35 73 7 Padova, Italy The kinetic ...

Progress in Colloid & Polymer Science, 1991

The rate of complexation of metal ions by lipophilic extractants solubilized in microheterogeneou... more The rate of complexation of metal ions by lipophilic extractants solubilized in microheterogeneous systems (micellar solutions or microemulasions) is shown to be of major interest from both fundamental and applied points of view. Results for copper complexing rates in different microheterogeneous systems indicate considerable decrease compared to typical values reported in homogeneous media, especially in the presence of a cationic surfactant.

ChemInform, 1995

ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance t... more ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Soil Biology and Biochemistry, 1991

HEf is a water-soluble humic constituent of molecular size compatible with uptake by plant roots.... more HEf is a water-soluble humic constituent of molecular size compatible with uptake by plant roots. In naturally-occurring humic material, HEI is usually encased in macrostructured, high-molecularweight, humic constituents (HSp) without biological activity. One prerequisite for any direct biological action by humic substances is therefore dissociation of the HECHSp structure. In order to investigate the above interaction, the effects of HEf and HSp on nitrate uptake and microsomal (M2+ K+) ATPax activity in oat roots were studied. HEf stimulated nitrate uptake with a peak value at I .O mg C I-', K+-stimulated ATPase activity of oat root microsomes, and H+ extrusion from roots, but it decreased ATP concentrations and did not influence 0, consumption. In contrast. HSp inhibited NO; transport al concentrations higher than 0.5 mg C I-'. and showed only negligible efkcts on the considered variables. These results suggest that HU stimulates NO; transport by activating K+-stimulate ATPase. whose activity lowered the ATP content of the cell. These effects are probably due both to the surfactant bchaviour of humic substances (critical micellc concentration is 0.25 mg C ml-' for HEf and 0.36 mg C ml-' for HSp) and to their biological activity. INTROIWCTION Naturally-occurring humic substances arc found in physiologically inactive forms. Their contribution to soil fertility is connected to improved chemical and mechanical properties (Whitehcad, 1963). although extcnsivc studies have demonstrated dircxt biological activity either favourablc or unfavourablc on plant metabolism (Vaughan and Malcolm. 1985). The most probable agents for these actions are the smail-mol~ular-size humic fractions taken up by roots and transported to metabolic targets (Vaughan

Journal of the Chemical Society, Perkin Transactions 1, 1988

Journal of the Chemical Society, Perkin Transactions 1, 1982

Chemistry – A European Journal

Journal of the American Chemical Society

The activity of many enzymes is regulated by associative processes. To model this mechanism, we r... more The activity of many enzymes is regulated by associative processes. To model this mechanism, we report here that the conformation of an unstructured bimetallic Zn(II) complex can be controlled by its inclusion in the cavity of a γ-cyclodextrin. This results in the formation of a catalytic bimetallic site for the hydrolytic cleavage of the RNA model substrate HPNP, whose reactivity is 30-fold larger with respect to the unstructured complex. Competitive inhibition with 1-adamantanecarboxylate displaces the metal complex from the cyclodextrin decreasing the reactivity.

ACS Catalysis

Recent studies have shown that gold nanoparticles (AuNPs) functionalized with Zn(II) complexes ca... more Recent studies have shown that gold nanoparticles (AuNPs) functionalized with Zn(II) complexes can cleave phosphate esters and nucleic acids. Remarkably, such synthetic nanonucleases appear to catalyze metal (Zn)-aided hydrolytic reactions of nucleic acids similar to metallonuclease enzymes. To clarify the reaction mechanism of these nanocatalysts, here we have comparatively analyzed two nanonucleases with a >10-fold difference in the catalytic efficiency for the hydrolysis of the 2hydroxypropyl-4-nitrophenylphosphate (HPNP, a typical RNA model substrate). We have used microsecond-long atomistic simulations, integrated with NMR experiments, to investigate the structure and dynamics of the outer coating monolayer of these nanoparticles, either alone or in complex with HPNP, in solution. We show that the most efficient one is characterized by coating ligands that promote a well-organized monolayer structure, with the formation of solvated bimetallic catalytic sites. Importantly, we have found that these nanoparticles can mimic two-metal-ion enzymes for nucleic acid processing, with Zn ions that promote HPNP binding at the reaction center. Thus, the two-metal-ion-aided hydrolytic strategy of such nanonucleases helps in explaining their catalytic efficiency for substrate hydrolysis, in accordance with the experimental evidence. These mechanistic insights reinforce the parallelism between such functionalized AuNPs and proteins toward the rational design of more efficient catalysts.

Nanomaterials

The biotin–avidin interaction is used as a binding tool for the conjugation of biomolecules for m... more The biotin–avidin interaction is used as a binding tool for the conjugation of biomolecules for more diverse applications; these include nanoparticle conjugation. Despite this, a thorough investigation on the different aggregates that may result from the interaction of biotinylated nanoparticles (gold nanoparticles, AuNPs, in this work) with avidin has not been carried out so far. In this paper, we address this problem and show the type of aggregates formed under thermodynamic and kinetic control by varying the biotinylated AuNP/avidin ratio and the order of addition of the two partners. The analysis was performed by also addressing the amount of protein able to interact with the AuNPs surface and is fully supported by the TEM images collected for the different samples and the shift of the surface plasmon resonance band. We show that the percentage of saturation depends on the size of the nanoparticles, and larger nanoparticles (19 nm in diameter) manage to accommodate a relatively ...

Nanomaterials

Drug-loaded, PEGylated, organic-modified silica (ORMOSIL) nanoparticles prepared by microemulsion... more Drug-loaded, PEGylated, organic-modified silica (ORMOSIL) nanoparticles prepared by microemulsion condensation of vinyltriethoxysilane (VTES) were investigated as potential nanovectors for cancer therapy. To target cancer stem cells, anti-CD44v6 antibody and hyaluronic acid (HA) were conjugated to amine-functionalized PEGylated ORMOSIL nanoparticles through thiol-maleimide and amide coupling chemistries, respectively. Specific binding and uptake of conjugated nanoparticles were studied on cells overexpressing the CD44v6 receptor. Cytotoxicity was subsequently evaluated in the same cells after the uptake of the nanoparticles. Internalization of nanocarriers loaded with the anticancer drug 3N-cyclopropylmethyl-7-phenyl-pyrrolo- quinolinone (MG2477) into cells resulted in a substantial increase of the cytotoxicity with respect to the free formulation. Targeting with anti-CD44v6 antibodies or HA yielded nanoparticles with similar effectiveness, in their optimized formulation.

European Journal of Organic Chemistry

Nanomaterials

The challenge to obtain plasmonic nanosystems absorbing light in the near infrared is always open... more The challenge to obtain plasmonic nanosystems absorbing light in the near infrared is always open because of the interest that such systems pose in applications such as nanotherapy or nanodiagnostics. Here we describe the synthesis in an aqueous solution devoid of any surfactant of Au-nanowires of controlled length and reasonably narrow dimensional distribution starting from Au-nanoparticles by taking advantage of the properties of glucosamine phosphate under aerobic conditions and substoichiometric nanoparticle passivation. Oxygen is required to enable the process where glucosamine phosphate is oxidized to glucosaminic acid phosphate and H2O2 is produced. The process leading to the nanosystems comprises nanoparticles growth, their aggregation into necklace-like aggregates, and final fusion into nanowires. The fusion requires the consumption of H2O2. The nanowires can be passivated with an organic thiol, lyophilized, and resuspended in water without losing their dimensional and opti...

Biopolymers, Jan 12, 2018

Gold nanoparticles are known to aggregate in the presence of proper multifunctional compounds. Fo... more Gold nanoparticles are known to aggregate in the presence of proper multifunctional compounds. For those larger than 3 nm, the process can be followed with the naked eye because the surface plasmon absorption band of the particles shifts to longer wavelengths and the solution color changes from red to blue. To exploit this property, we have used amino acids and peptides as crosslinking agents in ethanol at low µM concentrations. In the case of amino acids, we report a straightforward protocol for their colorimetric identification. We also report that the presence of precise secondary structure and conformational constraints in oligopeptides, directly influence their crosslinking ability. A discussion on the nature of the interactions that induce these phenomena is also reported.

Organic Preparations and Procedures International, 1991

Separ Sci Technol, 1982

The degradation with nitric acid of kerosene-type diluents of TBP in the reprocessing of nuclear ... more The degradation with nitric acid of kerosene-type diluents of TBP in the reprocessing of nuclear fuel leads to the formation of primary nitroalkanes. These, under acid conditions, may hydrolyze to hydroxamic acids, HA, which are well-known complex-ing agents of many metal ions, including Zr. The formation of very stable HA-Zr complexes has been proposed as a rationale for the retention of Zr in the diluents. However, the results of this study carried out in a model system, the acid-catalyzed conversion of 1-nitropropane to propanhydroxamic acid, and the subsequent hydrolysis to carboxylic acid and hydroxylamine—easily extensible to the actual reprocessing processes—indicate that in these systems the equilibrium concentration of hydroxamic acids attainable is too low (10 to 10 M) to account for the “zirconium retention” phenomenon.

Http Dx Doi Org 10 1080 15257770008033049, Sep 24, 2006

The hydrolytic activity of the 1,3,5-triaminocyclohexane derivatives TACH, TACI and TMCA complexe... more The hydrolytic activity of the 1,3,5-triaminocyclohexane derivatives TACH, TACI and TMCA complexed to Zn(II) and Cu(II) towards a model phosphoric ester and plasmid DNA has been evaluated by means of spectroscopic and gel-electrophoresis techniques. At conditions close to physiological, a prominent cleavage effect mediated by the nature of the ligand and metal ion was generally observed. TACI complexes are the most active in relaxing supercoiled DNA, the effect being explained by the affinity of the hydroxylated ligand for the nucleic acid. As indicated by the dependence of cleavage efficiency upon pH, Zn(II)-complexes act by a purely hydrolytic mechanism. In the case of Cu(II)-complexes, although hydrolysis should be prominent, involvement of an oxidative pathway cannot be completely ruled out.

Journal of the Chemical Society, Perkin Transactions 2, 1986

... or Zinc( 11) Roberto Fornasier, Daria Milani, Paolo Scrimin,' and Um... more ... or Zinc( 11) Roberto Fornasier, Daria Milani, Paolo Scrimin,' and Umberto Tonellato Centro 'Meccanismi di Reazioni Organiche del C. NR, lstituto di Chimica Organica, Universita di Pado va, 35 73 7 Padova, Italy The kinetic ...

Progress in Colloid & Polymer Science, 1991

The rate of complexation of metal ions by lipophilic extractants solubilized in microheterogeneou... more The rate of complexation of metal ions by lipophilic extractants solubilized in microheterogeneous systems (micellar solutions or microemulasions) is shown to be of major interest from both fundamental and applied points of view. Results for copper complexing rates in different microheterogeneous systems indicate considerable decrease compared to typical values reported in homogeneous media, especially in the presence of a cationic surfactant.

ChemInform, 1995

ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance t... more ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Soil Biology and Biochemistry, 1991

HEf is a water-soluble humic constituent of molecular size compatible with uptake by plant roots.... more HEf is a water-soluble humic constituent of molecular size compatible with uptake by plant roots. In naturally-occurring humic material, HEI is usually encased in macrostructured, high-molecularweight, humic constituents (HSp) without biological activity. One prerequisite for any direct biological action by humic substances is therefore dissociation of the HECHSp structure. In order to investigate the above interaction, the effects of HEf and HSp on nitrate uptake and microsomal (M2+ K+) ATPax activity in oat roots were studied. HEf stimulated nitrate uptake with a peak value at I .O mg C I-', K+-stimulated ATPase activity of oat root microsomes, and H+ extrusion from roots, but it decreased ATP concentrations and did not influence 0, consumption. In contrast. HSp inhibited NO; transport al concentrations higher than 0.5 mg C I-'. and showed only negligible efkcts on the considered variables. These results suggest that HU stimulates NO; transport by activating K+-stimulate ATPase. whose activity lowered the ATP content of the cell. These effects are probably due both to the surfactant bchaviour of humic substances (critical micellc concentration is 0.25 mg C ml-' for HEf and 0.36 mg C ml-' for HSp) and to their biological activity. INTROIWCTION Naturally-occurring humic substances arc found in physiologically inactive forms. Their contribution to soil fertility is connected to improved chemical and mechanical properties (Whitehcad, 1963). although extcnsivc studies have demonstrated dircxt biological activity either favourablc or unfavourablc on plant metabolism (Vaughan and Malcolm. 1985). The most probable agents for these actions are the smail-mol~ular-size humic fractions taken up by roots and transported to metabolic targets (Vaughan

Journal of the Chemical Society, Perkin Transactions 1, 1988

Journal of the Chemical Society, Perkin Transactions 1, 1982