Computational study of energetic nitrogen-rich derivatives of 1,4-bis(1-azo-2,4-dinitrobenzene)-iminotetrazole

The heats of formation (HOFs), electronic structure, energetic properties, and thermal stabilities for a series of 1,4-bis(1-azo-2,4-dinitrobenzene)-iminotetrazole derivatives with different substituents and substitution positions and numbers of nitrogen atoms in the nitrobenzene rings were studied using the DFT-B3LYP method. All the substituted compounds have higher HOFs than their parent compounds. As the number of nitrogen atoms in the nitrobenzene ring increases, the HOFs of the derivatives with the same substituent rise gradually. Replacing carbon atoms in the nitrobenzene with nitrogen atoms to form N–N bonds is very helpful in improving their HOFs. Most of the substituted compounds have higher HOMO–LUMO gaps than the corresponding unsubstituted compounds. Substitution of the –NO₂, –NF₂, or –ONO₂ group and an increase in the number of nitrogen atoms in the nitrobenzene rings are useful for enhancing their detonation performance. The substituents’ substitution is not favorable for improving thermal stability. Considering detonation performance and thermal stability, five compounds may be considered potential candidates for high energy density compounds (HEDCs).     

Computational investigation of the properties of double furazan-based and furoxan-based energetic materials

As a kind of promising energetic materials, the double furazan-based and furoxan-based compounds have raised concerns of many researchers in recent years. In this paper, the optimized structures, energetic properties, heat of formation (HOF), detonation properties, and bond dissociation energies of these compounds were calculated by density functional theory (DFT) method. The results show that the N-O bond, which is close to the adjacent coordinated oxygen atom in furoxan ring, is more fragile than the other N-O bonds in the ring. The double furazan-based derivatives are more stable than the double furoxan-based derivatives. All the titled compounds are divided into five groups because of the different substitute groups on both ends. The HOFs of the substances offer the order of 4 group (the both ends are 1,2,3,4-tetrazine ) ≈ 5 group (1,2,4,5-tetrazine) > 3 group (tetrazole) ≈ 1 group (1,2,3-triazole) > 2 group (1,2,4-triazole). All the title compounds also can be divided into three types with the different linkages, -N=N-, -N=N(O)-, and -NH-NH-. The results show that the HOFs of the compounds with different linkages obey the order -N=N- type > -N=N(O)- type> -NH-NH- type. For all titled compounds, bis(4-(1,2,4,5-tetrazin-3-yl)-1,2,5-oxadiazol-3-yl) diazene (E5) has the best gas-phase and solid-phase HOFs. The heat of detonation(Q) of bis(3-(1,2,3,4-tetrazin-5-yl)-1,2,5-oxidiazole-2 -oxide)diazene-1,2-diyl (B4) is the best of all titled compounds. The density of bis((3-2H-tetrazol-5-yl)-1,2,5-oxidiazole -2-oxide)oxidodiazene-1,2-diyl (A3) is the best and the second best is bis((4-2H-tetrazol-5-yl)-1,2,5-oxidiazol-3-yl) diazene (E3). The detonation velocities and detonation pressure of A3 and E3 are better than other titled compounds. 1,2-bis((4-2H-tetrazol-5-yl)-1,2,5 -oxidiazol-3-yl) diazene-1-oxide (D3) and 1,2-bis((4-2H-tetrazol-5-yl)-1,2,5-oxidiazol-3-yl) hydrazine (F3) have superior D and P with low sensitivity. The tetrazole ring plays a vital role in improving detonation velocities and pressure. The results can provide some foundational information for designing new high-density energetic materials.     

Theoretical design of energetic nitrogen-rich derivatives of 1,7-diamino-1,7-dinitrimino-2,4,6-trinitro-2,4,6-triazaheptane

The heats of formation (HOFs), energetic properties, and thermal stability of a series of 1,7-diamino-1,7-dinitrimino-2,4,6-trinitro-2,4,6-triazaheptane derivatives with different substituents, different numbers of substituents, and different original chains are found by using the DFT-B3LYP method. The results show that -NO₂ or -NH₂ is an effective substituent for increasing the gas-phase HOFs of the title compounds, especially -NO₂ group. As the numbers of substitutents increase, their HOFs enhance obviously. Increasing the length of original chain is helpful for improving their HOFs. The substitution of -NO₂ is useful for enhancing their detonation performances and the effects of the length of original chains on detonation properties are coupled with those of the substituents. An analysis of the BDE of the weakest bonds indicates that the substitution of the -NH₂ groups and replacing the -NO₂ groups of N-NO₂ by the -NH₂ groups are favorable for improving their thermal stability, while the substitution of -NO₂ and increasing the length of original chain decrease their thermal stability. Considering the detonation performance and thermal stability, seven compounds may be considered as the potential candidates of high energy density compounds.     

Theoretical investigation on the heats of formation and detonation performance in polydinitroaminocubanes

A series of polydinitroaminocubanes have been designed computationally. We calculated the heats of formation, the detonation velocity (D) and detonation pressure (P) of the title compounds by density function theory (DFT) with 6-311?G** basis set. The relationship between the heats of formation and the molecular structures is discussed. The result shows that all cubane derivatives have high and positive heats of formation, which increase with increasing number of dinitroamino groups. The detonation performances of the title compound were estimated by Kamlet-Jacobs equation, and the result indicated that most cubane derivatives have good detonation performance over RDX (hexahydro-1,3,5-trinitro-1,3,5-trizine) and HMX (1,3,5,7-tetranitro-1,3,5,7-tetraazacyclooctane). In addition, we also found that the heat of detonation (Q) is another very important impact in increasing detonation performance except density. The relative stabilities of the title compound are discussed in the terms of the calculated heats of formation, and the energy gaps between the frontier orbitals. The results have not only shown that these compounds may be used as high energy density compounds (HEDCs), but also provide some useful information for further investigation.     

Characterization of nitrogen-bridged 1,2,4,5-tetrazine-, furazan-, and 1H-tetrazole-based polyheterocyclic compounds: heats of formation, thermal stability, and detonation properties

The heats of formation (HOFs), thermal stability, and detonation properties for a series of nitrogen-bridged 1,2,4,5-tetrazine-, furazan-, and 1H-tetrazole-based polyheterocyclic compounds (3,6-bis(1H-1,2,3,4-tetrazole-5-ylamino)-1,2,4,5- tetrazine (TST), 3,6-bis(furazan-5-ylamino)-1,2,4,5-tetrazine (FSF), 3,4-bis(1,2,4,5- tetrazine-3-ylamino)-furazan (SFS), 3,4-bis(1H-1,2,3,4-tetrazole-5-ylamino)-furazan (TFT), 1,5-bis(1,2,4,5-tetrazine-3-ylamino)-1H-1,2,3,4-tetrazole (STS), and 1,5-bis(furazan-3-ylamino)-1H-1,2,3,4-tetrazole (FTF) derivatives) were systematically studied by using density functional theory. The results show that the -N(3) or -NHNH(2) group plays a very important role in increasing the HOF values of the derivatives. Among these series, the SFS derivatives have lower energy gaps, while the TFT derivatives have higher ones. Incorporation of the -NH(2) group into the FSF, SFS, STS, or FTF ring is favorable for enhancing its thermal stability, whereas the substitution of the -NHNH(2) group could increase the thermal stability of the TST, SFS, STS, or FTF ring. The calculated detonation properties indicate that the -NO(2) or -NF(2) is very helpful for enhancing the detonation performance for these derivatives. Considering the detonation performance and thermal stability, six derivatives may be regarded as promising candidates of high-energy density materials (HEDMs). These results provide basic information for the molecular design of novel HEDMs.     

Density functional calculations for a high energy density compound of formula C6H6?n (NO2) n

A series of polynitroprismanes, C(6)H(6-n )(NO(2))(n) (n?=?1-6) intended for use as high energy density compounds (HEDCs) were designed computationally. Their electronic structures, heats of formation, interactions between nitro groups, specific enthalpies of combustion, bond dissociation energies, and explosive performances (detonation velocities and detonation pressures) were calculated using density functional theory (DFT) with the 6-311 G** basis set. The results showed that all of the polynitroprismanes had high positive heats of formation that increased with the number of substitutions for the prismane derivatives, while the specific enthalpy of combustion decreased as the number of nitro groups increased. In addition, the range of enthalpy of combustion reducing is getting smaller. Interactions between ortho (vicinal) groups deviate from the group additivity rule and decrease as the number of nitro groups increases. In terms of thermodynamic stability, all of the polynitroprismanes had higher bond dissociation energies (BDEs) than RDX and HMX. Detonation velocities and detonation pressures were estimated using modified Kamlet-Jacobs equations based on the heat of detonation (Q) and the theoretical density of the molecule (ρ). It was found that ρ, D, and P are strongly linearly related to the number of nitro groups. Taking both their energetic properties and thermal stabilities into account, pentanitroprismane and hexanitroprismane are potential candidate HEDCs.     

Molecular design of aminopolynitroazole-based high-energy materials

The density functional theory (DFT) was employed to calculate the energetic properties of several aminopolynitroazoles. The calculations were performed to study the effect of amino and nitro substituents on the heats of formation, densities, detonation performances, thermal stabilities, and sensitivity characteristics of azoles. DFT-B3LYP, DFT-B3PW91, and MP2 methods utilizing the basis sets 6-31 G* and 6-311 G (2df, 3p) were adopted to predict HOFs via designed isodesmic reactions. All of the designed aminopolynitroazoles had heats of formation of >220 kJ mol(-1). The crystal densities of the aminopolynitroazoles were predicted with the cvff force field. All of the energetic azoles had densities of >1.83 g/cm(3). The detonation velocities and pressures were evaluated using the Kamlet-Jacobs equations, utilizing the predicted densities and heats of formation. It was found that aminopolynitroazoles have a detonation velocity of about 9.1 km/s and detonation pressure of 36 GPa. The bond dissociation energies for the C-NO(2) and N-NO(2) bonds were analyzed to investigate the stabilities of the designed molecules. The charge on the nitro group was used to assess impact sensitivity in the present study. The results obtained imply that the designed molecules are stable and are expected to be candidates for high-energy materials (HEMs).     

A computational study of ANTA and NTO derivatives

This work is a study of 5-amino-3-nitro-1,2,4-triazole (ANTA), 3-nitro-1,2,4-triazol-5-one (NTO), and nitrated derivatives of ANTA and NTO. RDX and TNT were studied for comparison. ANTA and NTO are low-sensitive high explosives with detonation properties comparable to 2,4,6-trinitrotoluene (TNT) and 1,3,5-trinitroperhydro-1,3,5-triazine (RDX). We showed previously that nitrated NTO and ANTA compounds, when used in a glycidyl azide polymer (GAP) matrix in rocket propellants, could give impulses above 2600 m/s and that the oxygen balance is positive. If used in aluminized explosives, the heat of detonation may be increased to a practical level significantly above RDX/aluminum compositions. Here, we use two different methods for sensitivity and two density functional theory functionals, B3LYP and M06-2X with the 6-31G(d) basis set, together with the complete basis set method CBS-4M. Calculations indicate that most of the nitrated derivatives have nearly equal sensitivity to RDX. Significantly different bond dissociation energies in the nitrimino functional group are predicted, although most models give much the same result.     

Theoretical studies of -NH2 and -NO2 substituted dipyridines

In this work, the experimental synthesized bipyridines 3,3'-Dinitro-2,2'-bipyridine (DNBPy), 3,3'-Dinitro-2,2'-bipyridine-1,1'-dioxide (DNBPyO), and (3-Nitro-2-pyridyl)(5-nitro-2-pyridyl) amine (NPyA), and a set of designed dipyridines that have similar frameworks but different linkages and substituents with NPyA were studied theoretically at the B3LYP/6-31G* level of density functional theory. The gas-phase heats of formation were predicted based on the isodesmic reactions and the condensed-phase heats of formation and heats of sublimation were estimated in the framework of the Politzer approach. The crystal densities have been computed from molecular packing. Results show that this method gives a good estimation of density in comparison with the available experimental data for DNBPy, DNBPyO, and NPyA. The predicted detonation velocities and pressures indicate that the performance of dipyridines linked with -O-, -NH-, or -CH(2)- bridges have not been improved compared with that of the directly linked dipyridines, but all derivatives have better detonation properties than DNBPy, DNBPyO, and NPyA because of the presence of more nitro groups. An analysis of the bond dissociation energies (BDEs) or the impact sensitivity (h (50)) suggests that introduction of different bridges but not substituents has little influence on thermal stability. The calculated h (50) may be more reliable than BDE for predicting stability. Four bridged bipyridines have quite good detonation performance and low sensitivity.     

1,3,5-Triazine multiselector systems: New tools for chiral discrimination

2-Hexylamino-4-[(S)-1-(1-naphthyl)ethylamino]-6-L-valyl-L-valyl-L-valine isopropylester-1,3,5-triazine (1), a molecule characterized by two different chiral selectors, and 2-hexylamino-4,6-bis-L-valyl-L-valyl-L-valine isopropylester-1,3,5-triazine (2) and 2-ethoxy-4-hexylamino-6-[(S)-1-(1-naphthyl) ethylamino]-1,3,5-triazine (3), systems in which a single kind of chiral selector is present, have been prepared. The enantiodiscriminating ability in solution of the three compounds toward the N-3,5-dinitrobenzoyl derivatives of 1-phenylethylamine (4) or valine methylester (5) has been investigated by ¹H nuclear magnetic resonance (NMR) spectroscopy: 1 shows an improved versatility, relative to 2 and 3, as a chiral solvating agent for NMR spectroscopy. On the basis of the indications obtained, the usefulness of 2-chloro-4-[(S)-1-(1-naphthyl)ethylamino]-6-L-val-L-val-L-valine isopropylester-1,3,5-triazine (1a), a direct precursor of 1, as chiral solvating agent for the determination by NMR of the enantiomeric compositions of derivatives of amines, amino alcohols, amino acids, and carboxyl acids bearing a 3,5-dinitrophenyl moiety, has been demonstrated. Chirality 9:113–121, 1997. © 1997 Wiley-Liss, Inc.     

Photosynthetic electron transport inhibition by 2-substituted 4-alkyl-6-benzylamino-1,3,5-triazines with thylakoids from wild-type and atrazine-resistant Chenopodium album

The effect of 2-benzylamino-1,3,5-triazines on photosynthetic electron transport (PET) was measured with thylakoids isolated from atrazine-resistant, wild-type Chenopodium album, and spinach to find novel 1,3,5-triazine herbicides bearing a strong PET inhibition. The PET inhibition assay with Chenopodium (wild-type and resistant), yielded a resistance ratio (R/W = I50 (resistant)/I50 (wild-type)) of 324 for atrazine while for benzylamino-1,3,5-triazine derivatives of diamino-1,3,5-triazines a R/W of 11 to 160 was found. The compounds having a benzylamino group at one of the amino groups in the diamino-1,3,5-triazines have a resistant ratio down to one half to 1/30 of the atrazine value. The average resistance ratio of 21 benzylamino derivatives of monoamino-1,3,5-triazines was found to be about 4.0. The inhibition of 21 benzylamino-1,3,5-triazines assayed with atrazine-resistant Chenopodium thylakoids, indicated by pI50 (R)-values, correlated well with the PET inhibition pI50 (W) of wild-type thylakoids from Chenopodium.     

Synthesis of glycosides in which the aglycon is an N-(Hydroxymethyl)amino-1,3,5-triazine derivative

The synthesis of analogues of the anti-tumour drug 2-[N-(hydroxymethyl)methylamino]-4,6-bis (dimethylamino)-1,3,5-triazine (HMPMM) in which the OH or a dimethylamino group is replaced by a carbohydrate has been explored. Triazinyl β-glycosides were readily prepared by reaction of sugars with trimethyl-triazinylammonium salts. These were made with one or two methylamino groups on the triazine for reaction with formaldehyde to give the cytotoxic NMeCH2OH group. However, reaction of the triazinyl glycosides with formaldehyde gave complex intractable mixtures. When the carbohydrate portion was changed to the fully protected 2,3,4,6-tetra-O-acetyl glucose a good yield of the 2-[N-(hydroxymethyl)methylamino]-4-(dimethylamino)-1,3,5-triazin-2-yl tetra-O-acetyl β-glucoside was obtained. However, de-acetylation using sodium methoxide also removed the N–CH2OH group. We are investigating protection of the base-sensitive N–CH2OH group as trialkylsilyl and benzyl ethers and are looking at de-acetylation methods that are more selective. We have prepared glycosides in which the sugar is joined through the oxygen of the NMeCH2OH group. Coupling of acetobromoglucose with HMPMM catalysed by silver salts was not successful. Although methyl and cyclohexyl derivatives of HMPMM may be produced in high yields by reaction of HMPMM with methyl and cyclohexyl alcohols under acidic catalysis, production of glycosides in this way gave poor yields. MNDO calculations on reactions of HMPMM helped us devise improved reaction conditions for the condensation of 2,3,4,6-tetra-O-acetyl glucose with HMPMM and its derivatives. The best procedure to generate one of the target glycosides is to react 2,3,4,6-tetra-O-acetyl glucose and formaldehyde with 2-methylamino- 4,6-bis(dimethylamino)-1,3,5-triazine. The β-glycoside product was de-acetylated using potassium carbonate in dry methanol. Abbreviations: HMM, hexamethylmelamine (2) or 2,4,6-tris(dimethylamino)-1,3,5-triazine; HMPMM, hydroxymethylpentamethylmelamine or 2-[N-(hydroxymethyl)-methylamino]-4,6-bis(dimethylamino)-1,3,5-triazine; PMM, Pentamethylmelamine or 2-methylamino-4,6-bis(dimethylamino)-1,3,5-triazine; TBMS, t-Butyldimethylsilyl; p-TSA, p-Toluenesulphonic acid This revised version was published online in November 2006 with corrections to the Cover Date.     

Quantum chemical studies on the aminopolynitropyrazoles

We have explored the geometric and electronic structures, band gap, thermodynamic properties, density, detonation velocity and detonation pressure of aminopolynitropyrazoles using the density functional theory (DFT) at the B3LYP/aug-cc-pVDZ level. The calculated detonation velocity and detonation pressure, stability and sensitivity of model compounds appear to be promising compared to the known explosives 3,4-dinitro-1 H-pyrazole (3,4-DNP), 3,5-dinitro-1 H-pyrazole (3,5-DNP), hexahydro-1,3,5-trinitro-1,3,5-triazinane (RDX) and octahydro-1,3,5,7-tetranitro-l,3,5,7-tetraazocane (HMX). The position of NH₂ group in the polynitropyrazoles presumably determines the structure, stability, sensitivity, density, detonation velocity and detonation pressure.     

Theoretical investigations on the structure, density, thermodynamic and performance properties of amino-, methyl-, nitroso- and nitrotriazolones

We have studied herein the effect of position and the number of -NO, -NO₂, -NH₂ and -CH₃ groups on the structure, stability, impact sensitivity, density, thermodynamic and detonation properties of triazolones by performing density functional theory calculations at the B3LYP/aug-cc-pVDZ level. The optimized structures, vibrational frequencies and thermodynamic values for triazolones have been obtained in their ground state. Kamlet-Jacob equations were used to calculate the detonation velocity and detonation pressure of model compounds. The detonation properties of NNTO (D 8.75 to 9.10 km/s, P 34.0 to 37.57 GPa), DNTO (D 8.80 to 9.05 km/s, P 35.55 to 38.27 GPa), ADNTO (D 9.01 to 9.42 km/s and P 37.81 to 41.10 GPa) and ANNTO (D 8.58 to 9.0 km/s, P 30.81 to 36.25 GPa) are compared with those of 1,3,5-trinitro-1,3,5-triazine (RDX) (D 8.75 km/s, P 34.70 Gpa) and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) (D 8.96 km/s, P 35.96 GPa). The designed compounds satisfy the criteria of high energy materials.     

Synthesis and evaluation of 1,3,5-triazine derivatives as sunscreens useful to prevent skin cancer

The incidence of skin cancers such as non-melanoma skin cancer and malignant melanoma has increased in the last few years mainly because of chronic exposure to ultraviolet (UV) radiation. Sunscreens protect the skin against harmful UV radiations; however, some limitations of these products justify the discovery of new UV filters. Novel 1,3,5-triazine derivatives (12a-h) obtained by the optimization of prototype resveratrol were synthesized and characterized. All compounds exhibited sun protection factor (SPF) and UVA protection factor (UVAPF) in the range of 3–17 and 3–13, respectively. These values were superior to resveratrol and the UV filter ethylhexyl triazone (EHT) currently available on the market. In addition, all compounds demonstrated in vitro antioxidant activity and thermal stability with the decomposition at temperatures above 236 °C. In conclusion, the novel 1,3,5-triazine derivatives have emerged as new UV filters with antioxidant effect useful to prevent skin cancer.     

Computational studies on polynitropurines as potential high energy density materials

As part of a search for high energy density materials (HEDMs), a series of purine derivatives with nitro groups were designed computationally. The relationship between the structures and the performances of these polynitropurines was studied. Density functional theory (DFT) at the B3LYP/6-311G** level was employed to evaluate the heats of formation (HOFs) of the polynitropurines by designing an isodesmic reaction method. Results indicated that the HOFs were influenced by the number and positions of substituent groups. Detonation properties were evaluated using the Kamlet–Jacobs equations, based on the theoretical densities and heats of formation of the polynitropurines. The relative stabilities of the polynitropurines were studied via the pyrolysis mechanism and the UB3LYP/6-311G** method. Homolysis of the ring–NO₂ bond is predicted to be the initial step in the thermal decomposition of these purine derivatives. Considering their detonation properties and relative stabilities, the tetranitropurine (D1) derivatives may be regarded as potential candidates for practical HEDCs. These results may provide useful information for further investigations.     

The search for new powerful energetic transition metal complexes based on 3,3′-dinitro-5,5′-bis-1,2,4-triazole-1,1′-diolate anion: a DFT study

In this study, employing a new high oxygen balance energetic 3,3′-dinitro-5,5′-bis-1,2,4-triazole-1,1′-diolate anion (DNBTDO) as the bidentate ligand, NH₃ and NH₂NO₂ as short energetic ligands, and Cu/Ni as the metal atoms, two series of novel energetic metal complexes were computationally designed. Their structures and properties were studied by density functional theory, electrostatic potential data, and molecular mechanics methods. The results showed that the designed metal complexes have high detonation performance and acceptable sensitivity: Cu/Ni(DNBTDO)(NH₂NO₂)₂ (A3/B3) have better detonation properties and lower sensitivity than the most powerful CHNO explosive hexanitrohexaazaisowurtzitane, Cu/Ni(DNBTDO)(NH₃)(NH₂NO₂) (A2/B2) have comparable energetic performance and sensitivity with 1,3,5,7-tetranitro-1,3,5,7-tetrazocane, Ni(DNBTDO)(NH₃)₂ (B1) has comparative energy level and sensitivity with 1,3,5-trinitro-1,3,5-triazinane. These five energetic metal complexes may be attractive to energetic materials researchers. Besides, both the energetic ligands and metal atoms could have a great influence on the structures, heats of formation, detonation properties, and stability of energetic metal complexes, and the effects are coupled with each other. This study may be helpful in the search for and development of new improved energetic materials.     

A theoretical study on the structures,thermodynamic properties and detonation performances of azidamines

A series of azidamines were studied at the B3LYP/6-311+G(2df) level of density functional theory. Thermodynamic properties were calculated and increased quantitatively with the increasing temperature as well as the number of azido groups. The azidamines are highly energetic with large enthalpies of formation. The detonation performances of the azidamines were evaluated and their performances are comparable to those of hexahydro-1,3,5-trinitro-1,3,5-trizine and 1,3,5,7-tetranitro-1,3,5,7-tetraazacyclooctane. However, they are sensitive to impact as well as halogen azides according to the small potential energy barriers.     

Theoretical design and characterisation on the fluorinated nitrophenyl azidotriazoles

Fluorinated molecules containing pyridyl- or phenyl-triazole moiety are useful materials in high-energy applications. In this work, based on the structure of N-(2, 4-dinitrophenyl)-3-azido-1H-1, 2, 4-triazole (I), two fluorinated nitrophenyl azidotriazoles (II and III) were designed by modifying I with the –CF₃ or –NF₂ group and were studied using the density functional theory (DFT). Compound I is a synthesised nitrophenyl azidotriazole with high heat of formation and acceptable detonation performance and thermal stability. Compared with I, the density and detonation properties of II and III are obviously improved, especially those of II. To better characterise II, the spectra (IR and UV/vis), thermal stability and pyrolysis mechanism were investigated. The thermal decomposition mechanism of II is similar to that of I, i.e. the azido triazole fragment is the initial spot of decomposition, while the thermal stability of II is better. The better performance of II suggests that it is worth further experimental investigations.     

Oligonucleotide N-alkylphosphoramidates: synthesis and binding to polynucleotides

A few different methods for the preparation of oligonucleotide N-alkylphosphoramidates were compared directly. One of these, involving the use of protected nucleoside phosphites as building blocks, provided the requisite N-alkylphosphoramidates via oxidation of the intermediate dinucleoside methyl phosphites with iodine in the presence of the appropriate alkylamine. This method was found to have several attractive features, including the use of building blocks identical with those employed for the synthesis of DNA and compatibility with procedures and instruments employed for the stepwise synthesis of oligonucleotides by solution and solid-phase methods. This procedure was used to make several di-, tri-, and tetranucleotide N-alkylphosphoramidates derived from deoxyadenosine and thymidine; alkyl substituents included N,N-dimethyl, N-butyl, N-octyl, N-dodecyl, and N-(5-aminopentyl). The aminoalkyl derivative of d(TpT) (24) was used to demonstrate the feasibility of introducing an intercalative agent to the alkylphosphoramidate moiety of such derivatives. The oligonucleotide N-alkylphosphoramidates were separated into their component diastereomers and characterized structurally by a number of techniques including circular dichroism, high-field 1H NMR spectroscopy, FAB mass spectrometry, and enzymatic digestion to authentic nucleosides and nucleotides. Physicochemical characterization of several di- and trinucleotide alkyl-phosphoramidates revealed that the adenine nucleotide analogues formed stable complexes with poly-(thymidylic acid). The stabilities of these complexes were found to increase with increasing chain length of the N-alkylphosphoramidate substituents. The finding that N-alkylphosphoramidate substituents can enhance the binding of certain oligonucleotides to their complementary polynucleotides suggests the existence of a novel source of polynucleotide affinity.