Interaction of synthetic analogs of distamycin and netropsin with nucleic acids. Does curvature of ligand play a role in distamycin-DNA interactions?

Distamycin and netropsin, a class of minor groove binding nonintercalating agents, are characterized by their B-DNA and A-T basespecific interactions. To understand the CQI I ~OIT~ ~ I ~ ~aOnMd ~c hemical basis of the above specificities, the DNA-binding characteristics of a novel synthetic analogue of distamycin have been studied. The analogue, mPD derivative, has the requisite charged end groups and a number of potential hydrogen-bonding loci equal to those of distamycin. The difference in the backbone curvatures of the ligands, distamycin, the mPD derivative, and NSC 101327 (another structurally analogous compound),is a major difference between these ligands. UV and CD spectrosoopic studies reported here show the following salient features: The mPD derivative recognizes only B-DNA, to which it binds via the minor groove. On the other hand, unlike distamycin, it binds with comparable affinities to A-T and G-C base pairs in a natural DNA. These DNA-binding properties are compared with those reported earlier for distamycin and NSC 101327 [Zimmer, Ch., & Wahnert, U. (1986) Prog. Biophys. Mol. Biol. 47, 31-1121. The backbone structures of these three ligands were compared to show the progressive decrease in curvatures in the order distamycin, mPD derivative, and NSC 101327. The plausible significance of the backbone curvature vis-&vis the characteristic B-DNA and AT-specific binding of distamycin is discussed. To our knowledge, this is the first attempt (with a model synthetic analogue) to probe the possible influence of backbone curvature upon the specificity of interactions of the distamycin class of groove-binding ligands with DNA.

Structure-Reactivity Correlations of Benzoin Alkyl Ethers. Structures of 2-Methoxy-1,2-diphenylethanone (I) and 2-Isopropoxy-1,2-diphenylethanone (II)

(I): C15H1402, Mr---226.27, triclinic, Pi,a=8.441 (2), b= 10.276 (1), c= 15.342 (2)A, a=91.02 (2), ~ t= 79.26 (2), y= 105.88 (2) °, V=1256.8 (4)A 3, Z=4, D,,= 1.209 (flotation in KI),D x - 1.195 g cm -3, #(Mo, 2 = 0.7107/~) = 0.44 cm -~,F(000) = 480, T= 293 K, R -- 0.060 for 1793 significant reflections. (II): C~THlsO2, Mr= 254.83, orthorhombic, Pca21, a=8.476 (1); b= 16.098 (3), c=10.802(3)A, V=1473.9 (5) A s, Z=4, Dm=1.161 (flotation in KI), Dx= 1.148gem -3, /~(Mo, 2=0.7107 A) =0.41 cm -~, F(000) = 544, T= 293 K, R = 0.071 for 867 significant reflections. Both (I) and (II) crystallize in a cisoid conformation for the carbonyl group and alkoxy groups. Compounds (I) and (II) are photostable on irradiation in the solid state in spite of the favourable conformation of the functional groups for intramolecular H abstraction. Absence of photoreaction of (I)and (II) in the solid state is rationalized in the light of unfavourable intramolecular geometry.

X-ray studies on crystalline complexes involving amino acids and peptides. XV. Crystal structures of L-lysine D-glutamate and L-lysine D-aspartate monohydrate and the effect of chirality on molecular aggregation

L-Lysine D-glutamate crystallizes in the monoclinic space group P2(1) with a = 4.902, b = 30.719, c = 9.679 A, beta = 90 degrees and Z = 4. The crystals of L-lysine D-aspartate monohydrate belong to the orthorhombic space group P2(1)2(1)2(1) with a = 5.458, b = 7.152, c = 36.022 A and Z = 4. The structures were solved by the direct methods and refined to R values of 0.125 and 0.040 respectively for 1412 and 1503 observed reflections. The glutamate complex is highly pseudosymmetric. The lysine molecules in it assume a conformation with the side chain staggered between the alpha-amino and the alpha-carboxylate groups. The interactions of the side chain amino groups of lysine in the two complexes are such that they form infinite sequences containing alternating amino and carboxylate groups. The molecular aggregation in the glutamate complex is very similar to that observed in L-arginine D-aspartate and L-arginine D-glutamate trihydrate, with the formation of double layers consisting of both types of molecules. In contrast to the situation in the other three LD complexes, the unlike molecules in L-lysine D-aspartate monohydrate aggregate into alternating layers as in the case of most LL complexes. The arrangement of molecules in the lysine layer is nearly the same as in L-lysine L-aspartate, with head-to-tail sequences as the central feature. The arrangement of aspartate ions in the layers containing them is, however, somewhat unusual. Thus the comparison between the LL and the LD complexes analyzed so far indicates that the reversal of chirality of one of the components in a complex leads to profound changes in molecular aggregation, but these changes could be of more than one type.

Interaction of metal ions with nucleic acids and related compounds. II. Studies on Au(III)-nucleic acid system

The nature of interaction of Au(III) with nucleic acids was studied by using methods such as uv and ir spectrophotometry, viscometry, pH titrations, and melting-temperature measurements. Au(III) is found to interact slowly with nucleic acids over a period of several hours. The uv spectra of native calf-thymus DNA 9pH 5.6 acetate buffer containing (0.01M NaCIO4) showed a shift in λ max to high wavelengths and an increase in optical density at 260 nm. There was a fourfold decrease in viscosity (expressed as ηsp/c). The reaction was faster at pH 4.0 and also with denatured DNA (pH 5.6) and whole yeast RNA (pH 5.6). The order of preference of Au(III) (as deduced from the time of completion of reaction) for the nucleic acids in RNA > denatured DNA > DNA. The reaction was found to be completely reversible with respect KCN. Infrared spectra of DNA-Au(III) complexes showed binding to both the phosphate and bases of DNA. The same conclusions were also arrived at by melting-temperature studies of Au(III)-DNA system. pH titrations showed liberation of two hydroxylions at r = 0.12 [r = moles of HAuCl4 added per mole of DNA-(P)] and one hydrogen ion at r = 0.5. The probable binding sites could be N(1)/N(7) of adenine, N(7) and/or C(6)O of guanine, N(3) of cytosine and N(3) of thymine. DNAs differing in their (G = C)-contents [Clostridium perfingens DNA(G = C, 29%), salmon sperm DNA (G + C, 42%) and Micrococcus lysodeikticus DNA(G + C, 29%), salmon sperm DNA (G = C, 72%)] behaved differently toward Au(III). The hyperchromicity observed for DNAs differing in (G + C)-content and cyanide reversal titrations indicate selectivity toward ( A + T)-rich DNA at lw values of r. Chemical analysis and job's continuous variation studies indicated the existence of possible complexes above and below r = 1. The results indicate that Au(III) ions probably bind to hte phosphate group in the initial stages of the reaction, particularly at low values of r, and participation of the base interaction also increases. Cross-linking of the two strands by Au(III) may take place, but a complete collapse of the doulbe helix is not envisaged. It is probable that tilting of the bases or rotaiton of the bases around the glucosidic bond, resulting in a significant distrotion of the double helix, might take place due to binding of Au(III) to DNA.

Effect of phenyl and phenolic acids on mevalonate-5-Phosphate decarboxylase if the brain

Phenyl and phenolic acids are known to inhibit metabolism of mevalonate in rat brain. The site of inhibition has been found to be mevalonate-5-pyrophosphate decarboxylase. Phenolic acids also inhibited mevalonate-5-phosphate kinase on preincubation. The kinetics showed that p-coumaric acid and isoferulic acid were competing with substrates, mevalonate-5-phosphate or mevalonate-5-pyre phosphate, whereas others showed an uncompetitive type of inhibition. Chlorophenoxyisobutyrate, a hypocholesterolaemic drug, had no effect on these enzymes. An improved method for the synthesis of mevalonate-5-phosphate and mevalonate-5-pyrophosphate, labeled at carbon-1, is described.

Reactions of tetrahalogeno-o-benzoquinones—Part VII. Reaction of alkyl-2-naphthols with tetrachloro-o-benzoquinone

Reaction of 8-methyl-2-naphthol (4a) with the quinone3 gave a mixture of 8-methyl-2,2-(tetrachlorohenylenedioxy)naphthalen-1(2H)-one (1b) and 8-methyl-1,1-(tetrachloro-o-phenylenedioxy)naphthalen-2(1H)-one (2b) in almost equal amounts. Similarly, reaction of the naphthols (4b), (4d) and (4e) with3 gave the corresponding dienones (1c &2c), (1e &2e) and (1f &2f) in almost equal amounts. Reaction of 8-t-butyl-2-naphthol (4c) with3 gave exclusively 8-t-butyl-2,2-(tetrachloro--henylenedioxy)-naphthalen-1(2H)-one (1d). Oxidation of 3-t-butyl-2-naphthol (4f) with3 gave a mixture of 3-t-butyl-2,2-(tetrachloro-o-phenylendioxy) nephthalene-1(2H)-one(1g) and 3-t-butyl-1,1-(tetrachloro--phenylenedioxy)naphthelen-2 (1H)-one (2g) in the ratio 1∶6. Thus, onlyt-butyl group exherts pronounced steric influence on the rearrangement observed in the reaction of β-naphthol with the quinone3. Structures of all the compounds have been established by spectral data.

Synthesis, crystal structures and magnetic behavior of two 3D coordination polymers using N-(4/3-arboxyphenyl)iminodiacetic acids as bridging ligands

Research on structure and magnetic properties of polynuclear metal complexes to understand the structural and chemical factors governing the electronic exchange coupling mediated by multi-atom bridging ligands is of growing interest. Hydrothermal treatment of Ni(NO3)(2)center dot 6H(2)O with N-(4-carboxyphenyl)iminodiacetic acid N-4(H(3)CPIDA)] at 150 degrees C yielded a 3D coordination polymer of general formula Ni-3{N-4( CPIDA)}(2)(H2O)(3)]center dot 6H(2)O (1). An analogous network of general formula Co-3{N-3(CPIDA)}(2)(H2O)(3)]center dot 3H(2)O (2) was synthesized using N-(3-carboxyphenyl) iminodiacetic acid N-3(H(3)CPIDA)] in combination with Co(NO3)(2)center dot 6H(2)O under identical reaction condition. Both the complexes contain trinuclear secondary building unit, and crystallized in monoclinic system with space groups C2/c (1) and P2(1)/c (2), respectively. Variable temperature magnetic characterization of these complexes in the temperature range of 2-300 K indicated the presence of overall ferromagnetic and antiferromagnetic behavior for 1 and 2, respectively. Density functional theory calculations (B3LYP functional) were performed for further insight on the trinuclear units to provide a qualitative theoretical interpretation on the overall magnetic behavior of the complexes 1 and 2. (C) 2010 Elsevier B.V. All rights reserved.

Supramolecular Chirality in Organogels: A Detailed Spectroscopic, Morphological, and Rheological Investigation of Gels (and Xerogels) Derived from Alkyl Pyrenyl Urethanes

This Article addresses the formation of chiral supramolecular structures in the organogels derived from chiral organogelator 1R (or 2R), and its mixtures with its enantiomer (1S) and achiral analogue 3 by extensive circular dichroism (CD) spectroscopic measurements. Morphological analysis by atomic force microscopy (AFM) and scanning electron microscopy (SEM) were complemented by the measurements of their bulk properties by thermal stability and rheological studies. Specific molecular recognition events (1/3 vs 2/3) and solvent effects (isooctane vs dodecane) were found to be critical in the formation of chiral aggregates. Theoretical studies were also carried out to understand the interactions responsible for the formation of the superstructures.