Leonardo Lo Presti

Leonardo Lo Presti
University of Milan | UNIMI · Department of Chemistry

PhD in Chemistry

About

155
Publications
28,580
Reads
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1,934
Citations
Citations since 2017
75 Research Items
1399 Citations
2017201820192020202120222023050100150200250
2017201820192020202120222023050100150200250
2017201820192020202120222023050100150200250
2017201820192020202120222023050100150200250
Introduction
My fields are experimental single-crystal diffractometry and computational chemistry, with main focus on chemical bonding in solids, molecular recognition and polymorphism. I also deal with molecular dynamics studies of small organic molecules in condensed phase, with the aim of elucidating the nucleation mechanism.
Additional affiliations
September 2016 - present
University of Milan
Position
  • Professor (Assistant)
Description
  • Course on "Rational Design and structural characterization of bioactive molecules" (4 ECTS)
March 2012 - present
University of Milan
Position
  • Professor (Assistant)
Description
  • Course on 'Advanced Physical Chemical Methods for investigating Molecular and Nanostructured systems', Bachelor degree in Chemistry (3 ECTS)
September 2008 - present
University of Milan
Position
  • Professor (Assistant)
Description
  • Course on 'Crystal Chemistry', MSc in Chemical Sciences (6 ECTS)

Publications

Publications (155)
Article
The nature of CH···X interactions in organic crystals, with X being an electronegative atom, has been the subject of extensive consideration with sometimes contradictory results and ensuing opinions. We perform statistical analysis on large databases of crystal structures retrieved from the Cambridge Structural Database. Crystals containing C–H don...
Article
While there is general consensus on the fundamental role played by strong hydrogen bonds (HB) in crystal packing, the significance of weak CH···X (X = N, O, S, F, Cl) interactions is still debated. Here, ~ 250 polymorph pairs of small molecules with no strong HB donors were retrieved from the Cambridge Structural Database. Statistical analysis tool...
Article
Full-text available
Parrinello−Rahman pressure-control algebra with an anisotropic external stress field, coupled with recently developed, accurate atom−atom potentials, has been incorporated into new modules of the Milano Chemistry Molecular Simulation (MiCMoS) computer program package for application in molecular dynamics (MD) simulations for organic crystals. Simul...
Article
Full-text available
D-glucose is a strategic chemical for agri-food and pharma industries, which are now exploiting an expected increase of 5% in the global investment round from 2020 to 2028. Despite such a broad industrial interest, the reasons behind room-p monomorphism in D-glucose are unclear. The crystal structure of α-D-glucose is provided here with an unpreced...
Article
Full-text available
Various boron-containing isocyanides have been efficiently synthesized from the corresponding enantiopure β-substituted β-amino boronic acid pinacol esters, without need for protecting group interconversion, through a two-step, purification-free procedure. They were employed in a variety of isocyanide-based multicomponent reactions, proving to be r...
Article
This work is focused on the understanding of the second harmonic generation (SHG) behavior of metal halogenides−saccharide-based compounds. Three new compounds were added to a list of such compounds that were previously analyzed by our group in order to deepen the understanding of the relationship between the SHG behavior of these materials and the...
Article
Full-text available
N-chloro-N'-(p-fluorophenyl)-benzamidine (NCLBA) is a N–halamine derivative which can easily release chlorine, for example when stimulated by high-energy photons. Despite the rich chemistry performed by N–halamines, the chemical properties of the N–Cl bond are poorly investigated. In this work, we determine the accurate charge density distribution...
Article
New peptidomimetics containing a β 2,2 ‐isoxazoline amino acid, i.e. 5‐(aminomethyl)‐3‐phenyl‐4,5‐dihydroisoxazole‐5‐carboxylic acid (Isox‐β 2,2 AA), were prepared and studied by NMR and theoretical calculation. Although similar amino acid derivatives have already been prepared via 1,3‐dipolar cycloaddition reaction, neither experimental details no...
Article
Various isocyanide‐based multicomponent reactions prove to be highly reliable when β‐substituted β‐amino boronic esters are employed as the amine component, allowing the efficient synthesis of unprecedented peptidomimetics and heteroatom‐rich boron‐containing small molecules. In particular, the scope of the Ugi reaction is widely exploited, to give...
Article
Full-text available
Cannabidiol‐C4 1 (CBD‐C4, cannabidibutol) is a natural product present in the extracts of Cannabis. Its isolation has not been reported to date. The aim of the proposed synthesis is to secure the availability of the pure compound, its spectroscopic characterization, and to confirm its presence in low amounts in the extracts. The enantioselective to...
Article
Full-text available
Treatment of 4-(2-hydroaminoalkylidenyl)- and 4-(2-hydroxyalkylidenyl)-substituted isoxazol-5(4H)-ones with catalytic amounts of [RuCl2(p-cymene)]2, without any additive, afforded pyrazole- and isoxazole-4-carboxylic acids, respectively. The presence of an intramolecular H-bond in these substrates was the key to divert the classical mechanism towar...
Article
Full-text available
Addressing the asymmetric synthesis of oxindole-based α-aminoboronic acids, instead of the expected products we disclosed the efficient homocoupling of oxindole-based N - tert -butanesulfinyl imines, with the generation of chiral, quaternary 1,2-diamines in a mild and completely stereoselective way. The obtained 3,3′-bisoxindole derivatives were fu...
Preprint
Full-text available
Addressing the asymmetric synthesis of oxindole-based a-amino boronic acids, instead of the expected products we disclosed the efficient homocoupling of oxindole-based N- tert -butanesulfinyl imines, with the generation of chiral, quaternary 1,2-diamines in a mild and completely stereoselective way. The obtained 3,3′-bisoxindoles derivatives were f...
Poster
Full-text available
Solvent screening and crystallizations allowed us to devise a simple and reproducible procedure to obtain single crystals of α-D-glucose from EtOH and hexane and to discover a new solvated form of β-D-glucose with acetonitrile. We also showed that, in some cases, low resolution XRD is not sufficient to detect the presence of disorder and we managed...
Presentation
Full-text available
How does crystallization begin? An answer to this apparently simple question is out of reach for current experimental techniques, which are blind to transient supramolecular aggregates that may occur in the no man’s land between a homogeneous liquid state and a suspension of crystal nuclei. Despite an increasing understanding of the thermodynamics...
Article
The science of organic crystals and materials has seen in a few decades a spectacular improvement from months to minutes for an X-ray structure determination and from single-point lattice energy calculations to dynamic simulation of hundreds of thousands of atoms. While diffraction experiments now proceed in compact, almost tabletop apparatus, theo...
Article
Full-text available
The Pd(II)-catalyzed reaction of N-allyl-2-aminophenols in the presence of PhI(OCOR)2 as the oxidant resulted in an alkoxyacyloxylation process, with the formation of functionalized dihydro-1,4-benzoxazines. The reaction performed in the absence of palladium catalyst switched to an intramolecular Diels–Alder reaction (IMDA) pathway, which was the r...
Article
Full-text available
An oxidative Pd‐catalyzed intra‐intermolecular dioxygenation of (aza‐)alkenols has been reported, with total regioselectivity. To study the stereoselectivity, different chiral ligands as well as different hypervalent‐iodine compounds have been compared. In particular, by using a C‐6 modified pyridinyl‐oxazoline (Pyox) ligand and hypervalent iodine...
Article
We here describe the first Cu-catalysed, diastereoselective 1,2-addition of 1,1-diborylmethane to chiral ketimines for the synthesis of quaternary stereocenters and spiro compounds. The method provides easy access to a range of chiral, highly functionalized compounds, namely oxindole-based β,β'-disubstituted β-amino boronates, boron-containing pept...
Article
Full-text available
In the last few decades optical imaging techniques based on nonlinear optical properties have been of interest for biosensing applications. This work focuses on two isostructural and isomorphous sugar-derived metal–organic frameworks (MOFs) with second-harmonic generation (SHG) properties, in order to investigate their possible application as biose...
Code
MiCMOS (Chemistry at Milano Molecular Simulation) is a set of Fortran computer programs for the simulation of the condensed states of small-molecule organic matter, using empirical potential energy schemes, ab initio-derived semiempirical energy calculation schemes, in a static approach analyzing only one point in phase space, or in an evolutionary...
Article
Full-text available
The experimental electron density distribution (EDD) of 1-methyluracil (1-MUR) was obtained by single crystal X-ray diffraction (XRD) experiments at 23 K. Four different structural models fitting an extensive set of XRD data to a resolution of (sinθ/λ)max = 1.143 Å −1 are compared. Two of the models include anharmonic temperature factors, whose inc...
Article
Full-text available
Nanocomposites are at the heart of the present nanotechnology revolution in several strategic fields, including Green Chemistry, sensors and pollutant remediation. The promising and extensively examined nanotitania photocatalysts have performances hampered by the rapid recombination of photogenerated charge carriers. To better understand these mate...
Article
We perform redundant x-ray diffraction versus temperature experiments in bulk transparent KTN. We find a violation of the standard perovskite cubic-to-tetragonal symmetry breaking at the Curie point in the form of an orthorhombic cell distortion. The lattice distortion spans coherently macroscopic volumes of the sample and is characterized by a neg...
Article
Full-text available
Multipolar refinements of structural models fitting extensive sets of X-ray diffraction (XRD) data from single crystals of 1,3-bis(dimethylamino)squaraine [SQ, C8H12N2O2] and its dihydrate [SQDH, C8H12N2O2•2H2O], collected at very low T (18 ± 1 K for SQ, 20 ± 1 K for SQDH), led to an accurate description of their crystal electron density distributi...
Article
Full-text available
Despite its role in spin density functional theory and it being the basic observable for describing and understanding magnetic phenomena, few studies have appeared on the electron spin density subtleties thus far. A systematic full topological analysis of this function is lacking, seemingly in contrast to the blossoming in the last 20 years of many...
Article
Full-text available
Large dark prismatic crystals (P -1) consisting of closely packed centrosymmetric [Cu(4,7-dichloroquinoline)2]2 Br4 binuclear units are formed when 4,7-dichloroquinoline (DCQ, C9H5NCl2) binds copper(II). Cu2+ adopts a strongly distorted square pyramidal coordination geometry, perturbed by electrostatic interactions with two axial µ-Br ligands actin...
Research Proposal
Full-text available
This is a working hypothesis - still to be proved - that focuses on the possible active lysosomal transport of 4-aminoquinoline compounds, which we hypothesize to be a suitable target for hydroxychloroquine-like drugs against SARS-CoV2 infection. We are studying 4-aminoquinoline antiplasmodials since some years now (see for example Cryst. Growth D...
Article
Full-text available
The application of various isonitrile-based multicomponent reactions to protected (2-oxoethyl)boronic acid (as the carbonyl component) is described. The Ugi reaction, both in the four components and in the four centers–three components versions, and the van Leusen reaction, proved effective at providing small libraries of MIDA-protected β-aminoboro...
Article
A set of 377 crystal structures extracted from the Cambridge Structural Database and matched to the experimental sublimation enthalpies of the corresponding materials is used to calibrate a new intermolecular potential field for organic compounds. The scheme includes usual R-6- R-12 Lennard-Jones dispersion-repulsion terms, with parameters for C, H...
Article
The palladium-catalyzed aminoazidation of aminoalkenes yielding azidomethyl-substituted nitrogen-containing heterocycles was developed. The procedure requires oxidative conditions and occurs at room temperature in the presence of hydrogen peroxide and NaN 3 as the azide source. These conditions provide selective exo-cyclization/azidation of the car...
Article
The CLP-dyncry molecular dynamics (MD) program suite and force field environment is introduced and validated with its ad hoc features for the treatment of organic crystalline matter. The package, stemming from a preliminary implementation on organic liquids (Gavezzotti & Lo Presti, 2019), includes modules for the preliminary generation of molecular...
Article
Full-text available
The indium-mediated allylation of novel 3-(2-Boc-hydrazono)indolin-2-one derivatives, followed by a palladium-catalysed carboamination reaction, is described to afford unprecedented spirocyclic oxindoles in good yields. The method provides an efficient access to both cis and trans diastereoisomers of highly functionalized compounds, bearing an N-Bo...
Presentation
Full-text available
Most Active Pharmaceutical Ingredients (API) can be prepared in various crystalline forms [1] displaying largely different physical/chemical properties and bioavailability. Salt formation represents the most common and simplest chemical way to modify the overall features but also the toxicity and biopharmaceutical availability of a drug substance....
Presentation
Full-text available
We present CLPdyn, a freely available code intended to perform Molecular Dynamics simulations of organic molecules in condensed phase.[1–3] CLPdyn can handle both continuous phases (liquids, crystals) and finite-size clusters (liquid droplets, nanoparticles), and exploits the thoroughly tested Coulomb-London-Pauli atom-atom intermolecular potential...
Conference Paper
Full-text available
We present CLPdyn, a freely available code intended to perform Molecular Dynamics simulations of organic molecules in condensed phase.[1–3] CLPdyn can handle both continuous phases (liquids, crystals) and finite-size clusters (liquid droplets, nanoparticles), and exploits the thoroughly tested Coulomb-London-Pauli atom-atom intermolecular potential...
Cover Page
Full-text available
Growing crystals in a gel matrix is possible to induce a huge variety of crystal shapes but also deep morphological and structural modifications, including disordered intergrowth crystals, macro- and micromorphology alterations, and gel inclusion phenomena. Moreover, thanks to their versatility, gel diffusion techniques represent a powerful tool to...
Article
Full-text available
A phenomenological study is carried out on a complex two-component diffusion-reacting system in gel, that is, the Cd-1,3-bis(4-pyridyl)propane (Cd-bpp) coordination polymer. The latter can exist in three solid forms, which exploit a 1:1 correspondence among the Cd/bpp ratio, the crystal structure and the crystal morphology (1/2: bipyramids; 2/3: ne...
Cover Page
Full-text available
The Front Cover shows a playful representation of the fascination to explore, that always moved science forward. In particular, the exploration of the Chemical Space is a challenging experience that excites creativity and enthusiasm of the organic chemists. The 2‐piperidine ethanol appears as a kite in the hands of a bold researcher to give vent to...
Article
The aminoarylation reaction of N-allylureas under oxidative palladium catalysis, in the absence of ligands and by using inexpensive H2O2 as the sole oxidant, occurs in a chemo- and regioselective fashion. This intramolecular process takes place via a 5-exo-trig cyclization, and represents an easy approach to 4-arylmethyl imidazolidinones.
Article
A sequence of seven reactions (stereocontrolled allylation, Mitsunobu reaction, ring closing metathesis and amino/amido intramolecular nucleophilic addition) efficiently convert the unexpensive starting 2‐piperidine ethanol in a small library of enatiomerically pure nitrogen containing compounds characterized by three new scaffolds that present a r...
Article
A procedure for the iodoamination of unfunctionalized olefins tethered to a tosyl‐protected NH‐group has been developed. The combined use of KI and H2O2 in aqueous medium was effective for the preparation of iodomethyl‐substituted nitrogen‐containing heterocycles. The selective exo‐trig iodocyclization provided 1,2‐bifunctional 5‐, 6‐, and 7‐member...
Article
In the context of personalized medicine, there is a growing interest in materials bearing at the same time diagnostic and therapy functions. This article reports a cheap and easily reproducible procedure to obtain materials with a high potential for these applications. Three new strontium iodide-fructose-based metal-organic frameworks with formulae...
Article
Five organic salts of the antiplasmodial drug piperaquine (PQ, C29H32Cl2N6) were synthesized and characterized by X–ray diffraction methods. The corresponding solubilities in water and acetic acid solutions were evaluated in the 20 – 50 ºC T range by UV–Vis spectroscopy, with the aim of elucidating how they depend on chemical, structural and thermo...
Article
The atom–atom intermolecular force field AA–CLP is applied to the Molecular Dynamics simulation of liquid nanoclusters of benzene, chloroform, methanol and pyridine. Bulk liquids are also simulated for validation and comparison with experimental data. The applied software has been produced de novo to deal with the unusual analytical form of the int...
Article
Full-text available
Two conformational crystal polymorphs of 3-diethylamino-4-(4-methoxyphenyl)-1,1-dioxo-4H-1l 6 ,2-thiazete-4-carbonitrile (DTC) have been analyzed in the 100 K-room temperature range by single crystal X-ray diffraction and high quality DFT calculations. DTC has strongly polar as well as aliphatic substituents but no hydrogen bonding groups, and thus...
Article
Following the discovery of a type III allosteric modulator of cyclin‐dependent kinase 2 (CDK2) characterized by a hexahydrocyclopenta[c]quinolone scaffold, three different series of its derivatives were synthesized and biologically evaluated. Docking of the synthesized compounds into the allosteric pocket of CDK2 allowed the elucidation of structur...
Data
Electronic Supplementary Information for "The TACO puzzle: a phase–transition mystery revisited", by Angelo Gavezzotti, Silvia Rizzato and Leonardo Lo Presti, Crystal Growth Des. 2018,DOI: 10.1021/acs.cgd.8b01461
Article
The organic salt (5–methyl–1–thia–5–azacyclo–octane–1–oxide) perchlorate (TACO) is known to undergo a single crystal to single crystal phase transition in the 276–298 K T range without change in the external shape of the sample. Despite extensive computational and experimental investigations, no safe conclusions about the transition mechanism could...
Article
Full-text available
A multicomponent Ugi reaction involving isatin, isocyanide and β-amino acid components has been developed. The reactions proceeded smoothly to give β-lactam-containing 3,3-disubstituted oxindoles in only one step and generally high yields. When chiral, non racemic, β-amino acids were used, products were obtained as enantiomerically pure β-lactams d...
Article
Flexible, stimuli-responsive metal-organic frameworks (MOFs) are very attractive as functional materials due to their wealth of tuneable structural and physical properties. Such compounds are commonly investigated by X-ray powder diffraction (XRPD) or spectroscopic techniques, as in most cases single-crystal X-ray diffraction experiments are not su...
Article
Full-text available
The rise of drug-resistant influenza A virus strains motivates the development of new antiviral drugs, with different structural motifs and substitution. Recently, we explored the use of a bicyclic (bicyclo[3.1.0]hexane) analogue of sialic acid that was designed to mimic the conformation adopted during enzymatic cleavage within the neuraminidase (N...
Data
Crystal structure of compound 15c. (PDF)
Data
Crystallographic information of compound 15c. (CIF)
Data
1H- and 13C- NMR spectra of compounds. (PDF)
Article
We developed two Ugi-type three-component reactions of spirooxindole-fused 3-thiazolines, isocyanides and either carboxylic acids or trimethylsilylazide, to give highly functionalized spirooxindole-fused thiazolidines. Two diverse libraries were generated using practical and robust procedures affording the products in typically good yields. The obt...
Article
Magnetic properties of open-shell systems depend on their unpaired electron density distribution. Accurate spin density (SD) is difficult to retrieve, both from polarized neutron diffraction (PND) data and from quantum approaches, and its interpretation is not trivial. The Source Function is a useful tool to interpret SD distributions and their acc...
Poster
Full-text available
Malaria is caused by the Plasmodium protozoa, which infect human through the bite of Anopheles mosquitoes. After entering the erythrocytes, Plasmodium digests the hemoglobin, releasing free toxic heme (Fe(III)-protoporphyrin-IX) into its digestive vacuole (DV). The dimerization of the free heme and its subsequent sequestration into triclinic hemozo...
Article
Full-text available
A concerted theoretical and experimental investigation of the silver/anatase hybrid nanocomposite, a very promising material for advanced sensing applications, is presented. We measure its exceptional electrochemical virtues in terms of current densities and reproducibility, providing their explanation at the atomic-scale level, and demonstrating h...
Article
The synthesis of analogues of the natural compound l-tricholomic acid and of its threo diastereoisomer was accomplished in order to explore their affinity for glutamate ionotropic receptors. In this study, fourteen new unnatural amino acids, characterized by a 3-hydroxy-▵2-isoxazoline or 3-hydroxy-▵2-pyrazoline-skeleton, were obtained exploiting, a...
Conference Paper
Full-text available
The Source Function (SF) tool [1] is applied to the analysis of the ab-initio spin density in two azido Cu(II) dinuclear complexes, where the azido group, acting as a coupler between the copper atoms, is linked to the metal centers either in an End-On or in an End-End fashion. The SF for the spin density [2] highlights to which extent the magnetic...
Article
The Source Function (SF) tool was applied to the analysis of the theoretical spin density in azido Cu II dinuclear complexes, where the azido group, acting as a coupler between the Cu II cations, is linked to the metal centres either in an end-on or in an end–end fashion. Results for only the former structural arrangement are reported in the presen...
Article
The possible occurrence of static/dynamic disorder at the Mg site in pyrope (Mg3Al2Si3O12), with or without anharmonic contribution to the thermal vibrations even at low temperatures, has been largely debated but conclusions were contrasting. Here a report is given on the experimental charge density distribution, ρEXP, of synthetic pyrope at T = 30...
Presentation
Full-text available
Malaria is due to protozoa of the genus Plasmodium, which infect human red blood cells and digest the host hemoglobin. Degradation of the latter in the acidic food vacuole (pH~ 5) releases free hematin (hydroxylated Fe protoporphyrin-IX, FePPIX(OH)), which is toxic to the parasite [1]. Therefore, Plasmodium deactivates hematin by promoting its crys...
Data
A survey of crystal structures including two organic compounds unable to form hydrogen bonding has been carried out using the Cambridge Structural Database. Such systems are common and numerous. Association modes mostly include stacking of flat systems, one of them usually being an aromatic hydrocarbon. “Alternate-ladder” (AL) and “slanted column”...
Article
A survey of crystal structures including two organic compounds unable to form hydrogen bonding has been carried out using the Cambridge Structural Database. Such systems are common and numerous. Association modes mostly include stacking of flat systems, one of them usually being an aromatic hydrocarbon. “Alternate-ladder” (AL) and “slanted column”...
Article
Full-text available
The surface functionalization of TiO2-based materials with alkylsilanes is attractive in several cutting-edge applications, such as photovoltaics, sensors, and nanocarriers for the controlled release of bioactive molecules. (3-Aminopropyl)triethoxysilane (APTES) is able to self-assemble to form monolayers on TiO2 surfaces, but its adsorption geomet...
Article
The availability of well characterized allosteric modulators is of crucial importance for investigating allosteric regulation of protein function. In a recently identified inactive conformation of CDK2 an open allosteric pocket has been detected and proposed as a site to accommodate allosteric inhibitors. Previous structure-based approaches allowed...
Cover Page
Full-text available
The inside cover picture shows the first small-molecule allosteric inhibitor of cyclin-dependent kinase 2 (CDK2) binding within an allosteric pocket in the proximity of the αC helix and distinct from the ATP binding site. The target compound was fully characterized through chemical synthesis, X-ray crystallography, modeling studies, and biological...
Presentation
Full-text available
The debate over nonmetal doping of TiO2, in particular N-doping, has extended for more than a decade. Although the benefits of these materials in terms of visible light absorption are often outweighed by a loss of stability and enhanced charge carrier recombination, the debate over N-doped TiO2 has spurred other more fundamental questions about the...
Data
It is known that N-doping of TiO2 is beneficial in terms of visible light absorption, but it is also often associated to detrimental effects,typically a loss of stability and an enhanced charge carrier recombination. The debate over N-doped TiO2 is still open and has spurred other more fundamental questions about the nature of TiO2 defects and the...