title: Novel therapeutic agents for bone resorption. Part 1. Synthesis and protonation thermodynamics of poly(amido-amine)s containing bis-phosphonate residues.
abstract: Two poly(amido-amine)s (oligoPAM and oligoNER) containing bis-phosphonate residues were obtained by a Michael-type polyaddition of pamidronate and neridronate to 1,4-bis(acryloyl)piperazine. The SEC (size-exclusion chromatography) and the MALDI-TOF (matrix assisted laser desorption ionization) analyses were consistent with the presence of oligomeric species (2-3 kDa) and with a narrow polydispersity index. The thermodynamic results (log Ks, -DeltaH(o) , and DeltaS(o) obtained at 25 degrees C in 0.15 M NaCl) of both the oligomers and the corresponding low molecular weight precursors were in line with a cluster structure formed during the protonation of the basic nitrogen in the pamidronate. The solubility of the oligoNER with a longer aliphatic chain was improved at high pHs, allowing the evaluation of their solution properties. Preliminary biological results show that both the oligomers do not negatively affect the in vitro viability, proliferation, and cellular activity of either normal animal or human osteoblasts.
authors.affiliation: Dipartimento di Scienze e Tecnologie Chimiche e dei Biosistemi, Università di Siena, Via Aldo Moro 2, I-53100 Siena, Italy. casolaro@unisi.it
authors.forename: Mario
authors.initials: M
authors.lastname: Casolaro
authors.forename: Ilaria
authors.initials: I
authors.lastname: Casolaro
authors.forename: Adriano
authors.initials: A
authors.lastname: Spreafico
authors.forename: Caterina
authors.initials: C
authors.lastname: Capperucci
authors.forename: Bruno
authors.initials: B
authors.lastname: Frediani
authors.forename: Roberto
authors.initials: R
authors.lastname: Marcolongo
authors.forename: Nicola
authors.initials: N
authors.lastname: Margiotta
authors.forename: Rosa
authors.initials: R
authors.lastname: Ostuni
authors.forename: Raniero
authors.initials: R
authors.lastname: Mendichi
authors.forename: Filippo
authors.initials: F
authors.lastname: Samperi
authors.forename: Takehiko
authors.initials: T
authors.lastname: Ishii
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ito
mesh_terms: D001862:Bone Resorption / Q000188:drug therapy*; D002470:Cell Survival / Q000187:drug effects; D004164:Diphosphonates / Q000737:chemistry* / Q000627:therapeutic use* / Q000633:toxicity; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D000077268:Pamidronate; D010879:Piperazines; D011199:Potentiometry; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013816:Thermodynamics; D014783:Viscosity
chemical_list: D004164:Diphosphonates; D010879:Piperazines; D000077268:Pamidronate