The secondary amine moieties of polyamines prepared by the reactions of aliphatic diamines, and 1,5-difluoro-2,4-dinitrobenzene, were nitrosated using sodium nitrite and aqueous concentrated sulfuric acid at low temperature. Released NO from these polymers, suspended in water or phosphate buffer solutions (PBS), was measured at increasing time intervals by colorimetric techniques using Griess Reagent. Similar tests were also conducted with model compounds. In general, both the model compounds and the corresponding polymers exhibited similar NO release profiles, with apparent half lives up to 88 h and 81 h, respectively. They were strongly dependent on the length of the alkyl chains derived from the primary amines used for the preparation of these NO-releasing materials. Results from in vitro studies using low molecular weight NO-releasing compounds with PC-12 cell are also reported. High concentration of NO induced neuronal cell death. On the other hand, low concentration of NO inhibited cell death induced by oxidative stress. This suggests that cell survival effect is NO-dependent.KEY WORDS: Nitrosated Polyamines / Nitric Oxide / Controlled Release / Cell Culture / Nitrogen monoxide, NO, more commonly known as nitric oxide, plays a critical role in a variety of biological functions.1-3 Towards the end of 1987, the discovery that mammalian cells synthesize nitric oxide, which regulates virtually every critical cellular function, has led to an explosion of research activities.4,5 For example, NO, which is produced from the amino acid L-Arginine in vivo, is involved in the regulation of neurotransmissions, blood pressure, and immune response.6 Nitric oxide can exist as a radical, NO , as a positively charged ion, NO þ (nitrosonium ion), and as nitroxyl anion (NO À ). 7 This allows NO to participate in numerous important biological functions mentioned above as well as others. Diseased states ensue when the bioavailability of NO, for a variety of reasons, becomes impaired. 8,9 Exogenous NO, derived from various families of NO-donors, has been used to ameliorate debilitating symptoms of a few of these diseases.
10A vast majority of NO-donors are low molecular weight compounds including: nitrates, nitrites, N-nitroso, C-nitroso, certain heterocycles, metal-NO complexes, and diazeniumdiolates. 10 Depending on the chemical nature of these compounds, NO is released spontaneously either in the presence or the absence of a catalyst. In the case of diazeniumdiolates, half-life of NO generation can be varied between 2 s to 56 h by changing the nature of the backbone to which the diazenuimdiolate moiety is attached.
11In contrast to the low molecular weight NO-donors, which have been investigated extensively, polymeric NO donors are new arrivals in this field. Since NO is known to prevent platelet aggregation, 12 NO generating polymers can be used as biomaterials, which are likely to come in contact with blood. In addition, the biocompatibility of implanted chemical sensors can be enhanced significantly by using NO-releasing...