Interaction of polyamines, their protonated salts and metal complexes with nucleic acid fragments

The paper describes our attempt to prove earlier conclusions on the conformation and inter-ionic interactions of protonated Put, Spd and 5pm cations, based initially on the X-ray and IR data of only two types of salts: hydrochlorides and hydrated monohydrogen phosphates. These two sets of salts composed at the beginning only of native polyamines (Put4, Spd3•4 and Spm343) were later on extended by their homologs (Put2, Spd3•3 and 5pm333), and further also by nitrates of Put and 5pm. The number of water molecules within homologous sets of crystalline monohydrogen phosphate salts, meets our predictions and depends on geometry and distribution of acceptor centers within dianions of monohydrogen phosphates. Underway are microcalorimetric measurements which should help us to understand the role of water molecules within specific networks of hydrogen bonds in single crystals of hydrated phosphates. Nitrate anions having planar structure and being stabilized by charge delocalization, interact in a completely different manner with protonated Put and 5pm cations, than the tetrahydrally oriented acceptor centers of chloride and phosphate anions. As a consequence, interesting similarities observed in proton-donor activities of NH3 group within pairs of hydrochlorides and phosphates do not exist any more in nitrate within the same PA cations. The last mentioned differences could be observed by measurements of melting midpoint temperature (Tm) of standard 5S rRNA solution after addition of equimilimolar amounts of hydrochloride or nitrate salt of Spm. The latter observation seems to indicate that counteranions could modulate within quite a wide range and in a special manner the interaction of protonated PA cations with different kinds of nucleic acids. The comparisons of the interactions of protonated and fully N-methylated sperminium cations (Spm4H4 and Mei0Spm4) with 5S rRNA seems to indicate that purely electrostatic attraction which is very often assumed as the main binding force between PAs and nucleic acids, in fact plays a much less significant role than to that of the networks of specific hydrogen bonds. I. INTRODUCTORY REMARKS ON NATURALLY OCCURRING POLYAMINES AND NATURAL PRODUCT CHEMISTRY Today, it is generally accepted that aliphatic biogenic amines, especially putrescine (Put), spermine (Spm) and spermidine (Spd) count among the most important natural products present in all living organisms. Here one may ask why this class of compounds has not so far been the subject of a plenary lecture at our symposia on natural product chemistry organized every second year since 1960. It is difficult to answer this simple question and although I am the one who has posed it, I am not sure I can answer it in a convincing way. Not giving the matter much thought, one could say not without reason, that there are probably other classes of natural products which deserve this distinction more. But is this the whole truth? Certainly not. I think that a majority of organic and bioorganic chemists, as well as biochemists, ignore or underestimate this class of compounds, like I ignored them untill recently, because of their exceptionally simple molecular structure consisting of nitrogencarbon chains without chiral centers or branches, and likewise simple chemistry leading to easy and efficient total syntheses. At first sight, it seems that synthetic and physical organic chemists have already studied all the interesting and important aspects of biogenic polyamines. In fact, the accumulation of knowledge on the chemistry and structure of polyamines, especially rapid in the last 20 years, has provided incentive for the biochemical,