F. Bellucci

Bio: F. Bellucci is an academic researcher. The author has contributed to research in topics: Resonance & Hydrogen bond. The author has an hindex of 3, co-authored 5 publications receiving 62 citations.

Structure of a nucleoside N1‐analogue of formycin B exhibiting the 'mid‐anti,C(3')‐endo' conformation

Abstract: 6-Benzyl-3-methyl1-(,8-D-ribofuranosyl)-7Hpyrazolo[4,3-d]pyrimidin-7-one, CIsH20N4Os, M r = 372.38, orthorhombic, P212121, a = 5 . 4 4 2 ( 1 ) , b = 13.387 (2), c = 23.759 (4)A, V = 1730.9 (6) A 3, z = 4, D x = 1.43 Mg m -3, Mo Ka, ,71. = 0.71069 A, /z = 0 . 1 0 m m -~, T = 2 9 4 K , F(000)=784, final R = 0.039 for 1154 observed reflections [ I> 20"(1)]. NNucleoside analogues of formycin A and B are studied as potential antiviral and antitumor agents. The conformational parameters of the present compound are: a C(3')-endo (3E/3T2) ribose conformation, a midanti glycosidic bond rotation [Z= 66.4 (4) °] and a gauche-trans conformation around the ribose C(4 ' ) C(5') bond. The hydrogen bonding in the crystal is analyzed in terms of graph formalism and it is found to correspond {according to the formalism of Kuleshova & Zorky IActa Cryst. (1980), B36, 2113-21151} to the F66(3,4,6) or F68(2,3,4,6) graphs according to whether the bifurcated hydrogen bonds are considered to be single or double bonds. Introduction. The C-nucleoside formycin A (I) is an isomer of adenosine, where imidazole replaces the pyrazole ring. Both formycin A and its analogue and metabolite formycin B (II) have been identified in naturally occurring systems; it has been found that they have definite antiviral and antitumor properties and are generally thought to be able to substitute for adenosine in several enzymatic reactions occurring at the nucleotide level. For these reasons a number of studies have been undertaken both on Cand N-nucleosides, the latter differing from the former in the substitution position of the ribofuranosyl ring. In particular, crystal and molecular structures of several C-nucleosides [formycin A.H20 (Prusiner, Brennan & Sundaralingam, 1973); formycin A.HBr (Koyama, Umezawa & Iitaka, 1974); formycin B and oxoformycin B (Koyama, Nakamura, Umezawa & Iitaka, 1976)1 and N-nucleosides (Altona & Sundaralingam, 1972, and references therein; Sprang, Scheller, Rohrer & Sundaralingam, 1978; Srikrishnam, Parthasarathy, De & Chheda, 1983) have been determined. 0108-2701/85/101449-04501.50 HO-~"~Z'" I H ~ u 2 " O \ I H H2°I g "

Predicting Hydrogen-Bond Strengths from Acid−Base Molecular Properties. The pKa Slide Rule: Toward the Solution of a Long-Lasting Problem

Abstract: Unlike normal chemical bonds, hydrogen bonds (H-bonds) characteristically feature binding energies and contact distances that do not simply depend on the donor (D) and acceptor (:A) nature. Instead, their chemical context can lead to large variations even for a same donor−acceptor couple. As a striking example, the weak HO−H···OH2 bond in neutral water changes, in acidic or basic medium, to the 6-fold stronger and 15% shorter [H2O···H···OH2]+ or [HO···H···OH]− bonds. This surprising behavior, sometimes called the H-bond puzzle, practically prevents prediction of H-bond strengths from the properties of the interacting molecules. Explaining this puzzle has been the main research interest of our laboratory in the last 20 years. Our first contribution was the proposal of RAHB (resonance-assisted H-bond), a new type of strong H-bond where donor and acceptor are linked by a short π-conjugated fragment. The RAHB discovery prompted new studies on strong H-bonds, finally leading to a general H-bond classification ...

Intramolecular Hydrogen Bonding in Medicinal Chemistry

Abstract: The formation of intramolecular hydrogen bonds has a very pronounced effect on molecular structure and properties. We study both aspects in detail with the aim of enabling a more rational use of this class of interactions in medicinal chemistry. On the basis of exhaustive searches in crystal structure databases, we derive propensities for intramolecular hydrogen bond formation of five- to eight-membered ring systems of relevance in drug discovery. A number of motifs, several of which are clearly underutilized in drug discovery, are analyzed in more detail by comparing small molecule and protein-ligand X-ray structures. To investigate effects on physicochemical properties, sets of closely related structures with and without the ability to form intramolecular hydrogen bonds were designed, synthesized, and characterized with respect to membrane permeability, water solubility, and lipophilicity. We find that changes in these properties depend on a subtle balance between the strength of the hydrogen bond interaction, geometry of the newly formed ring system, and the relative energies of the open and closed conformations in polar and unpolar environments. A number of general guidelines for medicinal chemists emerge from this study.

C‒H‒O Hydrogen Bonding in Crystals

Abstract: An overview is given on C–H···O hydrogen bonding in the solid state. Following a short survey of the early literature, the general properties of C–H···O bonding are discussed. The structural characteristics and some physical consequences of C–H···O bonds are described. A number of special systems are discussed in greater detail; these include water acceptors, inclusion complexes, and some biological structures.

Are short, low-barrier hydrogen bonds unusually strong?

Abstract: In a symmetric hydrogen bond (H-bond), the hydrogen atom is perfectly centered between the two donor atoms. The energy diagram for hydrogen motion is thus a single-well potential, rather than the double-well potential of a more typical H-bond, in which the hydrogen is covalently bonded to one atom and H-bonded to the other. Examples of symmetric H-bonds are often found in crystal structures, and they exhibit the distinctive feature of unusually short length: for example, the O−O distance in symmetric OHO H-bonds is found to be less than 2.5 A. In comparison, the O−O distance in a typical asymmetric H-bond, such as ROH···OR2, ranges from about 2.7 to 3.0 A. In this Account, we briefly review and update our use of the method of isotopic perturbation to search for a symmetric, centered, or single-well-potential H-bond in solution. Such low-barrier H-bonds are thought to be unusually strong, owing perhaps to the resonance stabilization of two identical resonance forms [A−H···B ↔ A···H−B]. This presumptive bon...

Hydrogen-Bonding: An Update

Abstract: This article focusses on the crystallographic research aimed at a better understanding of hydrogen bonds which has been published since January 1990. In the interest of continuity, earlier work is quoted when it relates to that published during this period.