Thermochemistry of aqueous solutions of alkylated nucleic acid bases. VI. Enthalpies of hydration of 2-alkyl-9-methyladenines

Enthalpies of solution in water, delta H0sol, and vant'Hoff enthalpies of sublimation, delta H0subl, were determined experimentally for a number of crystalline 2-alkyl derivatives of 9-methyladenine: m2(2,9)Ade, e2m9Ade, pr2m9Ade and but2m9Ade. Standard enthalpies of hydration, delta H0hydr derived from these data were corrected for the calculated cavity terms, delta H0cav, to yield enthalpies of interaction, delta H0int, of the solutes with their hydration shells. The apparent residual contribution of alkyl groups, R, to the enthalpy of interaction delta delta H0int (R) was found to increase linearly with the number of CH2 groups added upon alkyl substitution, whereas this contribution calculated per unit area of the water-accessible molecular surface, SB, of alkyl residues delta delta H0int (R): delta SB(R) appeared constant over the whole series of the compounds investigated. This indicates that alkyl groups substituted at the C(2) carbon atom of the adenine contribute additively to the van der Waals' part of the enthalpy of interaction and do not affect the electrostatic part of the energy of interaction of the solutes with their hydration shells.     

Binding of Substrates by Purine Nucleoside Phosphorylase (PNP) from Cellulomonas Sp. - Kinetic and Spectrofluorimetric Studies

Abstract

Dissociation constants and stoichiometry of binding for interaction of Cellulomonas sp. purine nucleoside phosphorylase with its substrates: inosine/guanosine, orthophosphate, guanine/hypoxanthine and D-ribose-1-phosphate were studied by kinetic and spectrofluorimetric methods.     

Two fluorogenic substrates for purine nucleoside phosphorylase,selective for mammalian and bacterial forms of the enzyme

Two nontypical nucleosides, 7-β-d-ribosyl-2,6-diamino-8-azapurine and 8-β-d-ribosyl-2,6-diamino-8-azapurine, have been found to exhibit moderately good, and selective, substrate properties toward calf and bacterial (Escherichia coli) forms of purine nucleoside phosphorylase (PNP). The former compound is effectively phosphorolysed by calf PNP and the latter by PNP from E. coli. Both compounds are fluorescent with λ_max ∼ 425 to 430 nm, but the reaction product, 2,6-diamino-8-azapurine, emits in a different spectral region (λ_max ∼ 363 nm) with nearly 40% yield, providing a strong fluorogenic effect at 350 to 360 nm.     

Characteristics of long-term survivors of brain metastases from lung cancer

Background and aim

Long-term survival of lung cancer patients with brain metastases (BM) is very rare. Our aim is to report the characteristics of patients who survived for at least three years after a BM diagnosis.

Materials and methods

Nineteen lung cancer patients who had survived ≥3 years after a BM diagnosis were identified in our database. Seven (37%) had undergone whole-brain radiotherapy (WBRT) only, five (26%) BM surgery + WBRT, three (16%) BM surgery + WBRT + BM radiosurgery, and four (21%) no WBRT (one, surgery; one, radiosurgery; two, BM surgery + radiosurgery). Their characteristics were compared with historical data for 322 lung cancer patients with BM (control group, CG), who had received WBRT between 1986 and 1997.

Results

Median survival from BM in long survivors group was 73 months (in CG – 4 months). Characteristics comparison: median age 55 vs. 58 (CG), p = 0.16; female sex 68% vs. 28% (CG), p = 0.003; RTOG/RPA class 1 – 75% vs. 13% (CG), p = 0.00001; adenocarcinoma histology 84% vs. 24% (CG), p < 0.00001; control of primary tumor 95% vs. 27% (CG), p < 0.00001; extracranial metastases 0 vs. 26% (CG), p = 0.01; single BM 63% vs. 9% (CG), p = 0.00001; surgery of BM 53% vs. 14% (CG), p = 0.00001.

Conclusions

Beside prognostic factors already recognized as favorable in patients with BM, the adenocarcinoma histology and female sex were prevalent in long-term survivors of BM from lung cancer.     

Fluorescence emission properties of 8-aza analogues of caffeine,theophylline, and related N-alkyl xanthines

Fluorescence emission properties of 8-azacaffeine, 8-azatheophylline and other N-alkylated 8-azaxanthines (8-azaXan) have been examined. It is shown that N-methylated 8-azaxanthines, as well as 8-azatheophylline, are highly fluorescent in aqueous medium as the neutral, and, in some instances, also as the monoanionic, forms. 8-Azacaffeine exhibits moderate emission, but its isomer, 1,3,8-trimethyl-8-azaXan, is highly fluorescent. All three 8-azaxanthines monomethylated on the triazole ring, as well as 8-azaxanthosine, exhibit increased acidity in the excited state. Some fluorescent pyrazolo[4,3-d]pyrimidine-5,7-diones, xanthine congeners of pyrazolo[4,3-d]pyrimidines, are also reported. Many of these are good fluorescent probes in enzymatic, receptor binding, and nucleic acid systems, some examples of which are presented. In particular, 8-azaXan is an excellent fluorescent probe for purine nucleoside phosphorylases, as a fluorogenic substrate in the reverse, synthetic pathway.     

Barrier to rotation and conformation of the -NR2 group in cytosine and its derivatives. Part II. Experimental and theoretical dipole moments of methylated cytosines.

The dipole moments of several cytosine, methylaminocytosine and dime-thylaminocytosine derivatives with and without an ortho methyl group were determined experimentally in dioxane and benzene. Calculations of total energies and dipole moments were performed by the CNDO/2 and INDO methods for sp2 and sp3 hybridization of exocyclic nitrogen for different values of rotational angle phiC-N. Comparison of the experimental dipole moments with those calculated for the energy minima suggests that the conformation of the dimethylamino group is not planar and differs from that found in cytosine. 1,5,7-Trimethylcytosine, with the dipole moment of 7 Deby units, was considered to be the model compound which closely reproduces the dipole moment of cytosine.