List of works - Paola Gratteri

2-Benzylpiperazine: A new scaffold for potent human carbonic anhydrase inhibitors. Synthesis, enzyme inhibition, enantioselectivity, computational and crystallographic studies and in vivo activity for a new class of intraocular pressure lowering age

scientific article published on 3 April 2018

4-Hydroxy-3-nitro-5-ureido-benzenesulfonamides Selectively Target the Tumor-Associated Carbonic Anhydrase Isoforms IX and XII Showing Hypoxia-Enhanced Antiproliferative Profiles

scientific article published on 28 November 2018

4-Substituted benzenesulfonamides featuring cyclic imides moieties exhibit potent and isoform-selective carbonic anhydrase II/IX inhibition

scientific article published on 19 October 2018

A highly pH-sensitive Zn(II) chemosensor.

scientific article published on 7 June 2010

A novel selective GABA(A) alpha1 receptor agonist displaying sedative and anxiolytic-like properties in rodents.

scientific article published on October 2005

Adsorptive stripping voltammetry for thiomersal assay

scientific article published on 01 February 1994

Anion and ion-pair binding by a G-2 poly(ethylene imine) dendrimer

scientific article published on 28 March 2013

Antagonism/Agonism modulation to build novel antihypertensives selectively triggering i1-imidazoline receptor activation

scientific article published on 3 April 2015

Appraisal of anti-protozoan activity of nitroaromatic benzenesulfonamides inhibiting carbonic anhydrases from Trypanosoma cruzi and Leishmania donovani

scientific article published on 01 December 2019

Aryl-4,5-dihydro-1H-pyrazole-1-carboxamide Derivatives Bearing a Sulfonamide Moiety Show Single-digit Nanomolar-to-Subnanomolar Inhibition Constants against the Tumor-associated Human Carbonic Anhydrases IX and XII

scientific article published on 09 April 2020

Assessment of human telomeric G-quadruplex structures using surface-enhanced Raman spectroscopy

scientific article published on 4 January 2017

Benzenesulfonamides Incorporating Flexible Triazole Moieties Are Highly Effective Carbonic Anhydrase Inhibitors: Synthesis and Kinetic, Crystallographic, Computational, and Intraocular Pressure Lowering Investigations

scientific article published on 21 November 2016

Benzodiazepine receptor ligands

scientific article published on 01 June 1999

Benzothiadiazinone-1,1-Dioxide Carbonic Anhydrase Inhibitors Suppress the Growth of Drug-Resistant Mycobacterium tuberculosis Strains

scientific article published in 2024

Benzoxaboroles as Efficient Inhibitors of the β-Carbonic Anhydrases from Pathogenic Fungi: Activity and Modeling Study

scientific article published on 20 October 2017

Binding of H+ and Zn(ii) ions with a new fluorescent macrocyclic phenanthrolinophane ⬇️

scientific article published on October 4, 2010

Bioisosteric Development of Multitarget Nonsteroidal Anti-Inflammatory Drug-Carbonic Anhydrases Inhibitor Hybrids for the Management of Rheumatoid Arthritis

scientific article published on 15 November 2019

Calixarenes Incorporating Sulfonamide Moieties: Versatile Ligands for Carbonic Anhydrases Inhibition

scientific article published in 2021

Cation, Anion and Ion-Pair Complexes with a G-3 Poly(ethylene imine) Dendrimer in Aqueous Solution

scientific article published on 16 May 2017

Central nicotinic receptors: structure, function, ligands, and therapeutic potential.

scientific article published in June 2007

Characterization of Sanguinaria canadensis L. fluid extract by FAB mass spectrometry

scientific article published on 01 January 1991

DNA Binding by a New Metallointercalator that Contains a Proflavine Group Bearing a Hanging Chelating Unit

scientific article published on 01 January 2008

Deciphering the Mechanism of Human Carbonic Anhydrases Inhibition with Sulfocoumarins: Computational and Experimental Studies

scientific article published on 03 May 2018

Design and optimization of the variables in the adsorptive stripping voltammetric determination of rufloxacin in tablets, human plasma and urine

scientific article published on 01 April 1995

Determinants for Tight and Selective Binding of a Medicinal Dicarbene Gold(I) Complex to a Telomeric DNA G-Quadruplex: a Joint ESI MS and XRD Investigation

scientific article

Determination of benzalkonium chloride in contact lens solutions by positive-ion fast atom bombardment mass spectrometry

scientific article published on 01 January 1989

Differential electrolytic potentiometry (DEP) with twin silver—silver sulphide membrane electrodes in micro titration of quaternary ammonium compounds

scientific article published on 01 January 1988

Discovery of New Sulfonamide Carbonic Anhydrase IX Inhibitors Incorporating Nitrogenous Bases.

scientific article published on 21 November 2017

Discovery of β-Adrenergic Receptors Blocker-Carbonic Anhydrase Inhibitor Hybrids for Multitargeted Antiglaucoma Therapy

scientific article published on 13 June 2018

Dithiocarbamates effectively inhibit the β-carbonic anhydrase from the dandruff-producing fungus Malassezia globosa.

scientific article published on 27 December 2016

Dual-tail arylsulfone-based benzenesulfonamides differently match the hydrophobic and hydrophilic halves of human carbonic anhydrases active sites: Selective inhibitors for the tumor-associated hCA IX isoform.

scientific article published on 10 April 2018

Enhancement of the tail hydrophobic interactions within the carbonic anhydrase IX active site via structural extension: Design and synthesis of novel N-substituted isatins-SLC-0111 hybrids as carbonic anhydrase inhibitors and antitumor agents

scientific article published on 02 November 2018

Experimental design and multivariate calibration in the development, set-up and validation of a differential pulse polarographic and UV spectrophotometric method for the simultaneous plasmatic determination of the therapeutic metronidazole–pefloxac

article

Experimental design in the development of voltammetric method for the assay of omeprazole

article

Experimental design strategies in the optimization and robustness testing of adsorptive stripping voltammetric conditions for kynurenic acid determination

scientific article published on 01 June 1997

FILO (field interaction ligand optimization): a simplex strategy for searching the optimal ligand interaction field in drug design.

scientific article published in January 2001

From random to rational: A discovery approach to selective subnanomolar inhibitors of human carbonic anhydrase IV based on the Castagnoli-Cushman multicomponent reaction

scientific article published on 26 August 2019

Halogenated isophthalamides and dipicolineamides: the role of the halogen substituents in the anion binding properties

scientific article published on 05 June 2020

Hypericins and thioredoxin reductase: Biochemical and docking studies disclose the molecular basis for effective inhibition by naphthodianthrones

scientific article

Inhibition of Malassezia globosa carbonic anhydrase with phenols

scientific article published on 18 March 2017

Inhibition of the β-carbonic anhydrase from the dandruff-producing fungus Malassezia globosa with monothiocarbamates.

scientific article published in December 2017

Insights into docking and scoring neuronal alpha4beta2 nicotinic receptor agonists using molecular dynamics simulations and QM/MM calculations.

scientific article published in November 2009

Interaction of a gold(i) dicarbene anticancer drug with human telomeric DNA G-quadruplex: solution and computationally aided X-ray diffraction analysis

Interactions of selected gold(iii) complexes with DNA G quadruplexes

scientific article published on 01 February 2015

Lipoyl-Homotaurine Derivative (ADM_12) Reverts Oxaliplatin-Induced Neuropathy and Reduces Cancer Cells Malignancy by Inhibiting Carbonic Anhydrase IX (CAIX).

scientific article

Metal ion binding by a G-2 poly(ethylene imine) dendrimer. Ion-directed self-assembling of hierarchical mono- and two-dimensional nanostructured materials.

scientific article

Modeling and biological investigations of an unusual behavior of novel synthesized acridine-based polyamine ligands in the binding of double helix and G-quadruplex DNA.

scientific article published on December 2010

N-Nitrosulfonamides as Carbonic Anhydrase Inhibitors: A Promising Chemotype for Targeting Chagas Disease and Leishmaniasis

scientific article published on 27 November 2018

Natural Polyphenols Selectively Inhibit β-Carbonic Anhydrase from the Dandruff-Producing Fungus Malassezia globosa: Activity and Modeling Studies.

scientific article published on 25 March 2018

New Rigid Nicotine Analogues, Carrying a Norbornane Moiety, Are Potent Agonists of α7 and α3* Nicotinic Receptors

scientific article published on 08 February 2019

Novel 4/3-((4-oxo-5-(2-oxoindolin-3-ylidene)thiazolidin-2-ylidene)amino) benzenesulfonamides: Synthesis, carbonic anhydrase inhibitory activity, anticancer activity and molecular modelling studies.

scientific article published in August 2017

Novel Diamide-Based Benzenesulfonamides as Selective Carbonic Anhydrase IX Inhibitors Endowed with Antitumor Activity: Synthesis, Biological Evaluation and In Silico Insights.

scientific article published on 20 May 2019

Novel indolin-2-one-based sulfonamides as carbonic anhydrase inhibitors: Synthesis, in vitro biological evaluation against carbonic anhydrases isoforms I, II, IV and VII and molecular docking studies.

scientific article published on 11 January 2017

Novel insights on saccharin- and acesulfame-based carbonic anhydrase inhibitors: design, synthesis, modelling investigations and biological activity evaluation

scientific article published on 01 December 2020

Perfluoroalkyl Substances of Significant Environmental Concern Can Strongly Inhibit Human Carbonic Anhydrase Isozymes

scientific article published on 04 March 2020

Phosphorus vs sulphur: discovery of benzenephosphonamidates as new versatile sulfonamide-mimic chemotypes acting as carbonic anhydrase inhibitors

scientific article published on 14 December 2018

Polypharmacology of epacadostat: a potent and selective inhibitor of the tumor associated carbonic anhydrases IX and XII

scientific article published on 01 May 2019

Role of the Benzodioxole Group in the Interactions between the Natural Alkaloids Chelerythrine and Coptisine and the Human Telomeric G-Quadruplex DNA. A Multiapproach Investigation.

scientific article published on 17 November 2017

Searching for a reliable orientation of ligands in their binding site: comparison between a structure-based (Glide) and a ligand-based (FIGO) approach in the case study of PDE4 inhibitors

scientific article published on 01 March 2005

Selective binding and fluorescence sensing of diphosphate in H2OviaZn2+-induced allosteric regulation of the receptor structure

scientific article published on 07 November 2011

Selenols: a new class of carbonic anhydrase inhibitors

scientific article published on 01 January 2019

Sensing Zn2+ in Aqueous Solution with a Fluorescent Scorpiand Macrocyclic Ligand Decorated with an Anthracene Bearing Tail

scientific article published on 17 March 2020

Solid State and Solution Study on the Formation of Inorganic Anion Complexes with a Series of Tetrazine-Based Ligands

scientific article published on 16 June 2019

Solution NMR Structure of a Ligand/Hybrid-2-G-Quadruplex Complex Reveals Rearrangements that Affect Ligand Binding

Solution NMR Structure of a Ligand/Hybrid-2-G-Quadruplex Complex Reveals Rearrangements that Affect Ligand Binding.

scientific article published on 19 May 2017

Solution and Solid-State Analysis of Binding of 13-Substituted Berberine Analogues to Human Telomeric G-quadruplexes

scientific article

Spectroscopic, Molecular Modeling, and NMR-Spectroscopic Investigation of the Binding Mode of the Natural Alkaloids Berberine and Sanguinarine to Human Telomeric G-Quadruplex DNA

article

Steroids interfere with human carbonic anhydrase activity by using alternative binding mechanisms

scientific article published on 01 December 2018

Synthesis and benzodiazepine receptor affinity of pyrazolo[1,5-a]pyrimidine derivatives. 3. New 6-(3-thienyl) series as alpha 1 selective ligands.

scientific article

Synthesis and biological evaluation of novel 9-heteroaryl substituted 7-chloro-4,5-dihydro-4-oxo-1,2,4-triazolo[1,5-a]quinoxaline-2-carboxylates (TQX) as (R,S)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) receptor antagonists.

scientific article

Synthesis and carbonic anhydrase inhibition of polycyclic imides incorporating N-benzenesulfonamide moieties

scientific article published on 29 July 2017

Synthesis, SAR and in vitro evaluation of new cyclic Arg-Gly-Asp pseudopentapeptides containing a s-cis peptide bond as integrin alphavbeta3 and alphavbeta5 ligands.

scientific article

Synthesis, biological evaluation and computational studies of novel iminothiazolidinone benzenesulfonamides as potent carbonic anhydrase II and IX inhibitors.

scientific article published on 31 January 2018

Tales of the Unexpected: The Case of Zirconium(IV) Complexes with Desferrioxamine

scientific article published on 02 June 2019

The [Au(9-methylcaffein-8-ylidene)2]+ / DNA Tel23 System: Solution, Computational and Biological Studies.

scientific article

The crystal structure of human telomeric DNA complexed with berberine: an interesting case of stacked ligand to G-tetrad ratio higher than 1:1

scientific article

The three-tails approach as a new strategy to improve selectivity of action of sulphonamide inhibitors against tumour-associated carbonic anhydrase IX and XII

publication published on 01 December 2022

Total syntheses of casuarine and its 6-O-alpha-glucoside: complementary inhibition towards glycoside hydrolases of the GH31 and GH37 families

scientific article

Use of Innovative (Micro)Extraction Techniques to Characterise Harpagophytum procumbens Root and its Commercial Food Supplements

scientific article

X-Ray diffraction analyses of the natural isoquinoline alkaloids Berberine and Sanguinarine complexed with double helix DNA d(CGTACG) ⬇️

scientific article published on March 22, 2011

α,γ-Diketocarboxylic Acids and Their Esters Act as Carbonic Anhydrase IX and XII Selective Inhibitors

scientific article published on 19 February 2019

List of works by Paola Gratteri

2-Benzylpiperazine: A new scaffold for potent human carbonic anhydrase inhibitors. Synthesis, enzyme inhibition, enantioselectivity, computational and crystallographic studies and in vivo activity for a new class of intraocular pressure lowering age

4-Hydroxy-3-nitro-5-ureido-benzenesulfonamides Selectively Target the Tumor-Associated Carbonic Anhydrase Isoforms IX and XII Showing Hypoxia-Enhanced Antiproliferative Profiles

4-Substituted benzenesulfonamides featuring cyclic imides moieties exhibit potent and isoform-selective carbonic anhydrase II/IX inhibition

A highly pH-sensitive Zn(II) chemosensor.

A novel selective GABA(A) alpha1 receptor agonist displaying sedative and anxiolytic-like properties in rodents.

Adsorptive stripping voltammetry for thiomersal assay

Anion and ion-pair binding by a G-2 poly(ethylene imine) dendrimer

Antagonism/Agonism modulation to build novel antihypertensives selectively triggering i1-imidazoline receptor activation

Appraisal of anti-protozoan activity of nitroaromatic benzenesulfonamides inhibiting carbonic anhydrases from Trypanosoma cruzi and Leishmania donovani

Aryl-4,5-dihydro-1H-pyrazole-1-carboxamide Derivatives Bearing a Sulfonamide Moiety Show Single-digit Nanomolar-to-Subnanomolar Inhibition Constants against the Tumor-associated Human Carbonic Anhydrases IX and XII

Assessment of human telomeric G-quadruplex structures using surface-enhanced Raman spectroscopy

Benzenesulfonamides Incorporating Flexible Triazole Moieties Are Highly Effective Carbonic Anhydrase Inhibitors: Synthesis and Kinetic, Crystallographic, Computational, and Intraocular Pressure Lowering Investigations

Benzodiazepine receptor ligands

Benzothiadiazinone-1,1-Dioxide Carbonic Anhydrase Inhibitors Suppress the Growth of Drug-Resistant Mycobacterium tuberculosis Strains

Benzoxaboroles as Efficient Inhibitors of the β-Carbonic Anhydrases from Pathogenic Fungi: Activity and Modeling Study

Binding of H+ and Zn(ii) ions with a new fluorescent macrocyclic phenanthrolinophane ⬇️

Bioisosteric Development of Multitarget Nonsteroidal Anti-Inflammatory Drug-Carbonic Anhydrases Inhibitor Hybrids for the Management of Rheumatoid Arthritis

Calixarenes Incorporating Sulfonamide Moieties: Versatile Ligands for Carbonic Anhydrases Inhibition

Cation, Anion and Ion-Pair Complexes with a G-3 Poly(ethylene imine) Dendrimer in Aqueous Solution

Central nicotinic receptors: structure, function, ligands, and therapeutic potential.

Characterization of Sanguinaria canadensis L. fluid extract by FAB mass spectrometry

DNA Binding by a New Metallointercalator that Contains a Proflavine Group Bearing a Hanging Chelating Unit

Deciphering the Mechanism of Human Carbonic Anhydrases Inhibition with Sulfocoumarins: Computational and Experimental Studies

Design and optimization of the variables in the adsorptive stripping voltammetric determination of rufloxacin in tablets, human plasma and urine

Determinants for Tight and Selective Binding of a Medicinal Dicarbene Gold(I) Complex to a Telomeric DNA G-Quadruplex: a Joint ESI MS and XRD Investigation

Determination of benzalkonium chloride in contact lens solutions by positive-ion fast atom bombardment mass spectrometry

Differential electrolytic potentiometry (DEP) with twin silver—silver sulphide membrane electrodes in micro titration of quaternary ammonium compounds

Discovery of New Sulfonamide Carbonic Anhydrase IX Inhibitors Incorporating Nitrogenous Bases.

Discovery of β-Adrenergic Receptors Blocker-Carbonic Anhydrase Inhibitor Hybrids for Multitargeted Antiglaucoma Therapy

Dithiocarbamates effectively inhibit the β-carbonic anhydrase from the dandruff-producing fungus Malassezia globosa.

Dual-tail arylsulfone-based benzenesulfonamides differently match the hydrophobic and hydrophilic halves of human carbonic anhydrases active sites: Selective inhibitors for the tumor-associated hCA IX isoform.

Enhancement of the tail hydrophobic interactions within the carbonic anhydrase IX active site via structural extension: Design and synthesis of novel N-substituted isatins-SLC-0111 hybrids as carbonic anhydrase inhibitors and antitumor agents

Experimental design and multivariate calibration in the development, set-up and validation of a differential pulse polarographic and UV spectrophotometric method for the simultaneous plasmatic determination of the therapeutic metronidazole–pefloxac

Experimental design in the development of voltammetric method for the assay of omeprazole

Experimental design strategies in the optimization and robustness testing of adsorptive stripping voltammetric conditions for kynurenic acid determination

FILO (field interaction ligand optimization): a simplex strategy for searching the optimal ligand interaction field in drug design.

From random to rational: A discovery approach to selective subnanomolar inhibitors of human carbonic anhydrase IV based on the Castagnoli-Cushman multicomponent reaction

Halogenated isophthalamides and dipicolineamides: the role of the halogen substituents in the anion binding properties

Hypericins and thioredoxin reductase: Biochemical and docking studies disclose the molecular basis for effective inhibition by naphthodianthrones

Inhibition of Malassezia globosa carbonic anhydrase with phenols

Inhibition of the β-carbonic anhydrase from the dandruff-producing fungus Malassezia globosa with monothiocarbamates.

Insights into docking and scoring neuronal alpha4beta2 nicotinic receptor agonists using molecular dynamics simulations and QM/MM calculations.

Interaction of a gold(i) dicarbene anticancer drug with human telomeric DNA G-quadruplex: solution and computationally aided X-ray diffraction analysis

Interactions of selected gold(iii) complexes with DNA G quadruplexes

Lipoyl-Homotaurine Derivative (ADM_12) Reverts Oxaliplatin-Induced Neuropathy and Reduces Cancer Cells Malignancy by Inhibiting Carbonic Anhydrase IX (CAIX).

Metal ion binding by a G-2 poly(ethylene imine) dendrimer. Ion-directed self-assembling of hierarchical mono- and two-dimensional nanostructured materials.

Modeling and biological investigations of an unusual behavior of novel synthesized acridine-based polyamine ligands in the binding of double helix and G-quadruplex DNA.

N-Nitrosulfonamides as Carbonic Anhydrase Inhibitors: A Promising Chemotype for Targeting Chagas Disease and Leishmaniasis

Natural Polyphenols Selectively Inhibit β-Carbonic Anhydrase from the Dandruff-Producing Fungus Malassezia globosa: Activity and Modeling Studies.

New Rigid Nicotine Analogues, Carrying a Norbornane Moiety, Are Potent Agonists of α7 and α3* Nicotinic Receptors

Novel 4/3-((4-oxo-5-(2-oxoindolin-3-ylidene)thiazolidin-2-ylidene)amino) benzenesulfonamides: Synthesis, carbonic anhydrase inhibitory activity, anticancer activity and molecular modelling studies.

Novel Diamide-Based Benzenesulfonamides as Selective Carbonic Anhydrase IX Inhibitors Endowed with Antitumor Activity: Synthesis, Biological Evaluation and In Silico Insights.

Novel indolin-2-one-based sulfonamides as carbonic anhydrase inhibitors: Synthesis, in vitro biological evaluation against carbonic anhydrases isoforms I, II, IV and VII and molecular docking studies.

Novel insights on saccharin- and acesulfame-based carbonic anhydrase inhibitors: design, synthesis, modelling investigations and biological activity evaluation

Perfluoroalkyl Substances of Significant Environmental Concern Can Strongly Inhibit Human Carbonic Anhydrase Isozymes

Phosphorus vs sulphur: discovery of benzenephosphonamidates as new versatile sulfonamide-mimic chemotypes acting as carbonic anhydrase inhibitors

Polypharmacology of epacadostat: a potent and selective inhibitor of the tumor associated carbonic anhydrases IX and XII

Role of the Benzodioxole Group in the Interactions between the Natural Alkaloids Chelerythrine and Coptisine and the Human Telomeric G-Quadruplex DNA. A Multiapproach Investigation.

Searching for a reliable orientation of ligands in their binding site: comparison between a structure-based (Glide) and a ligand-based (FIGO) approach in the case study of PDE4 inhibitors

Selective binding and fluorescence sensing of diphosphate in H2OviaZn2+-induced allosteric regulation of the receptor structure

Selenols: a new class of carbonic anhydrase inhibitors

Sensing Zn2+ in Aqueous Solution with a Fluorescent Scorpiand Macrocyclic Ligand Decorated with an Anthracene Bearing Tail

Solid State and Solution Study on the Formation of Inorganic Anion Complexes with a Series of Tetrazine-Based Ligands

Solution NMR Structure of a Ligand/Hybrid-2-G-Quadruplex Complex Reveals Rearrangements that Affect Ligand Binding

Solution NMR Structure of a Ligand/Hybrid-2-G-Quadruplex Complex Reveals Rearrangements that Affect Ligand Binding.

Solution and Solid-State Analysis of Binding of 13-Substituted Berberine Analogues to Human Telomeric G-quadruplexes

Spectroscopic, Molecular Modeling, and NMR-Spectroscopic Investigation of the Binding Mode of the Natural Alkaloids Berberine and Sanguinarine to Human Telomeric G-Quadruplex DNA

Steroids interfere with human carbonic anhydrase activity by using alternative binding mechanisms

Synthesis and benzodiazepine receptor affinity of pyrazolo[1,5-a]pyrimidine derivatives. 3. New 6-(3-thienyl) series as alpha 1 selective ligands.

Synthesis and biological evaluation of novel 9-heteroaryl substituted 7-chloro-4,5-dihydro-4-oxo-1,2,4-triazolo[1,5-a]quinoxaline-2-carboxylates (TQX) as (R,S)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) receptor antagonists.

Synthesis and carbonic anhydrase inhibition of polycyclic imides incorporating N-benzenesulfonamide moieties

Synthesis, SAR and in vitro evaluation of new cyclic Arg-Gly-Asp pseudopentapeptides containing a s-cis peptide bond as integrin alphavbeta3 and alphavbeta5 ligands.

Synthesis, biological evaluation and computational studies of novel iminothiazolidinone benzenesulfonamides as potent carbonic anhydrase II and IX inhibitors.

Tales of the Unexpected: The Case of Zirconium(IV) Complexes with Desferrioxamine

The [Au(9-methylcaffein-8-ylidene)2]+ / DNA Tel23 System: Solution, Computational and Biological Studies.

The crystal structure of human telomeric DNA complexed with berberine: an interesting case of stacked ligand to G-tetrad ratio higher than 1:1

The three-tails approach as a new strategy to improve selectivity of action of sulphonamide inhibitors against tumour-associated carbonic anhydrase IX and XII

Total syntheses of casuarine and its 6-O-alpha-glucoside: complementary inhibition towards glycoside hydrolases of the GH31 and GH37 families

Use of Innovative (Micro)Extraction Techniques to Characterise Harpagophytum procumbens Root and its Commercial Food Supplements