Interaction of proflavin with deoxytetraribonucleoside triphosphate 5'-d(ApGpCpT): thermodynamic analysis from (1)H NMR data]

Temperature relationships of chemical shifts of protons of proflavin mixed with deoxytetraribonucleoside triphosphate 5'-d(ApGpCpT) in water solution were investigated on impulse NMR spectrometer (500 MHz). Procedure is suggested for calculating values of mole fractions of various associates in solution as a function against temperature. Free energies of Gibbs, entalpy and entropy were determined in the reactions of complex formation 1:1, 1:2, 2:1 of proflavin with tetranucleotide. The results point to a significant role of hydrophobic interactions during the formation of dye--tetramere duplex complexes.     

The NMR Structure of Estrone (Es)-tethered Tandem DNA Duplex: [d(5′pCAGCp3′)-Es] + [Es-d(5′ pTCCA3′)]: d(5′ pTGGAGCTG3′)

Abstract

The solution structure of an estrone (Es)-tethered tandem DNA duplex consisting of two Estethered tetranucleotides and a target octameric DNA sequence is reported. The structure of this Es-tethered tandem duplex has been compared with a corresponding natural tandem duplex without estrones. The T_m of the 3′-Es-tethered tetranucleotide part of the tandem duplex increases by 5°C, whereas the T_m of the 5′-Es-tethered tetranucleotide part increases by 7°C, compared with the corresponding natural counterpart. The NMR structures of both the Es-tethered tandem duplex and the natural counterpart have been based on 24 experimental NMR constraints per residue. Despite the fact that there is considerable distortion at the junction of two Es-tethered tetranucleotides in the major groove of the Es-tethered DNA duplex compared to the natural counterpart, both duplexes do take up B-type DNA structures. It is likely that the spatial proximity of two Es residues, and the resulting hydrophobic interaction between them might be responsible for the increase of the thermal stability of the Es-tethered tandem duplex in comparison with the natural counterpart.     

Crystal structure of the self-complementary 5''-purine start decamer d(GCACGCGTGC) in the A-DNA conformation. II.

The crystal structure of the alternating 5'-purine start decamer d(GCGCGCGCGC) was found to be in the left-handed Z-DNA conformation. Inasmuch as the A.T base pair is known to resist Z-DNA formation, we substituted A.T base pairs in the dyad-related positions of the decamer duplex. The alternating self-complementary decamer d(GCACGCGTGC) crystallizes in a different hexagonal space group, P6(1)22, with very different unit cell dimensions a = b = 38.97 and c = 77.34 A compared with the all-G.C alternating decamer. The A.T-containing decamer has one strand in the asymmetric unit, and because it is isomorphous to some other A-DNA decamers it was considered also to be right-handed. The structure was refined, starting with the atomic coordinates of the A-DNA decamer d(GCGGGCCCGC), by use of 2491 unique reflections out to 1.9-A resolution. The refinement converged to an R value of 18.6% for a total of 202 nucleotide atoms and 32 water molecules. This research further demonstrates that A.T base pairs not only resist the formation of Z-DNA but can also assist the formation of A-DNA by switching the helix handedness when the oligomer starts with a 5'-purine; also, the length of the inner Z-DNA stretch (d(CG)n) is reduced from an octamer to a tetramer. It may be noted that these oligonucleotide properties are in crystals and not necessarily in solutions.     

Crystal structure of an RNA duplex r(gugucgcac)(2) with uridine bulges.

The crystal structure of a nonamer RNA duplex with a uridine bulge in each strand, r(gugucgcac)(2), was determined at 1.4 A resolution. The structure was solved by multiple anomalous diffraction phasing method using a three-wavelength data set collected at the Advanced Protein Source and refined to a final R(work)/R(free) of 21.2 %/23.4 % with 33,271 independent reflections (Friedel pairs unmerged). The RNA duplex crystallized in the tetragonal space group P4(1)22 with two independent molecules in the asymmetric unit. The unit cell dimensions are a=b=47.18 A and c=80.04 A. The helical region of the nonamer adopts the A-form conformation. The uridine bulges assume similar conformations, with uracils flipping out and protruding into the minor groove. The presence of the bulge induces very large twist angles (approximately +50 degrees) between the base-pairs flanking the bulges while causing profound kinks in the helix axis at the bulges. This severe twist and the large kink in turn produces a very narrow major groove at the middle of the molecule. The ribose sugars of the guanosines before the bulges adopt the C2'-endo conformation while the rest, including the bulges, are in the C3'-endo conformation. The intrastrand phosphate-phosphate (P-P) distance of the phosphate groups flanking the bulges (approximately 4.4 A) are significantly shorter than the average P-P distance in the duplex (6.0 A). This short distance between the two phosphate groups brings the non-bridging oxygen atoms close to each other where a calcium ion is bound to each strand. The calcium ions in molecule 1 are well defined while the calcium ions in molecule 2 are disordered.     

Visualization of drug-nucleic acid interactions at atomic resolution. IX. Structures of two N,N-dimethylproflavine: 5-iodocytidylyl (3'-5') guanosine crystalline complexes

This paper describes two complexes containing N,N-dimethylproflavine and the dinucleoside monophosphate, 5-iodocytidylyl (3'-5') guanosine (iodoCpG). The first complex is triclinic, space group P1, with unit cell dimensions a = 11.78 A, b = 14.55 A, c = 15.50 A, alpha = 89.2 degrees, beta = 86.2 degrees, gamma = 96.4 degrees. The second complex is monoclinic, space group P21, with a = 14.20 A. b = 19.00 A, c = 20.73 A, beta = 103.6 degrees. Both structures have been solved to atomic resolution and refined by Fourier and least squares methods. The first structure has been refined anisotropically to a residual of 0.09 on 5,025 observed reflections using block diagonal least squares, while the second structure has been refined anisotropically to a residual of 0.13 on 2,888 reflections with full matrix least squares. The asymmetric unit in both structures contains two dimethylproflavine molecules and two iodoCpG molecules; the first structure has 16 water molecules (a total of 134 non-hydrogen atoms), while the second structure has 18 water molecules (a total of 136 non-hydrogen atoms). Both structures demonstrate intercalation of dimethylproflavine between base-paired iodoCpG dimers. In addition, dimethylproflavine molecules stack on either side of the intercalated duplex, being related by a unit cell translation along b and a axes, respectively. The basic structural feature of the sugar-phosphate chains accompanying dimethylproflavine intercalation in both structures is the mixed sugar puckering pattern: C3' endo (3'-5') C2' endo. This same structural information is again demonstrated in the accompanying paper, which describes a complex containing dimethylproflavine with deoxyribo-CpG. Similar information has already appeared for other "simple" intercalators such as ethidium, acridine orange, ellipticine, 9-aminoacridine, N-methyl-tetramethylphenanthrolinium and terpyridine platinum. "Complex" intercalators, however, such as proflavine and daunomycin, have given different structural information in model studies. We discuss the possible reasons for these differences in this paper and in the accompanying paper.     

1H-NMR structural analysis of ethidium bromide complexation with self-complementary deoxytetranucleotides 5′-d (ApCpGpT), 5′-d (ApGpCpT), and 5′-d (TpGpCpA) in aqueous solution

Complexation of the trypanocidal drug, ethidium bromide (EB), and the self-complementary deoxytetraribonucleoside triphosphates, 5′-d(ApCpGpT), 5′-d(ApGpCpT), and 5′-d(TpGpCpA), in aqueous salt solution has been investigated using one-dimensional and two-dimensional 500/600 MHz ¹H-nmr spectroscopy. Six hundred megahertz two-dimensional homonuclear ¹H-nmr spectroscopy (nuclear Overhauser effect spectroscopy) was used for a qualitative determination of the structures of EB binding with the deoxytetranucleotides. Concentration dependencies of proton chemical shifts of the molecules have been measured at constant temperatures (T = 303 or 308 K). Different successive schemes of complex formation between the dye molecule and the tetranucleotides have been examined by taking into account various molecular associations in solution, viz., 1:1, 1:2, 2:1 and 2:2 complexes. Equilibrium reaction constants and the limiting proton chemical shifts in the complexes have been determined. The relative contributions of different types of complexes in the equilibrium mixture have been determined and special features of the dynamic equilibrium have been revealed by analysis of chemical shifts as a function of both the dye and tetranucleotide concentrations. The present analysis leads to the conclusion that EB binds preferentially to the pyrimidine-purine sites of the tetranucleotide duplexes. The results show that the energy of EB binding depends on the base content in the pyrimidine-purine sites of the tetramers and on the nucleotide residuals flanking the preferential site. The most favorable structures of the 1:2 and 2:2 complexes of the dye with the tetranucleotides have been constructed using calculated values of induced chemical shifts of EB protons in conjunction with intermolecular nuclear Overhauser effects. The structures of the EB:tetranucleotide complexes depend on tetramer base sequence and are characterized by differences in helix parameters. © 1996 John Wiley & Sons, Inc.     

Molecular and crystal structure of (1----3)-alpha-D-glucan triacetate.

A crystal and molecular structure for GTA I, the low temperature polymorph of (1----3)-alpha-D-glucan triacetate, is proposed on the basis of X-ray diffraction analysis of well-oriented films, combined with stereochemical model refinement. The unit cell is monoclinic with parameters a = 30.17 A, b = 17.42 A, c (fibre axis) = 12.11 A, and beta = 90 degrees C. The probable space group is P2(1) with b axis unique. Six molecular chains pass through the unit cell with alternating polarity and with three independent chains comprising the asymmetric unit. The chain axes are located in a hexagonal packing arrangement. The chain backbone conformation is a left-handed, three-fold helix, but all nine O(6) acetyl groups of the asymmetric unit are in non-equivalent rotational positions. The most probable structure is indicated by X-ray residuals R = 0.261 and R" = 0.283, based on 62 reflection intensities (41 observed and 21 unobserved).     

Crystal structure of the topoisomerase II poison 9-amino-[N-(2-dimethylamino)ethyl]acridine-4-carboxamide bound to the DNA hexanucleotide d(CGTACG)2.

The structure of the complex formed between d(CGTACG)(2) and the antitumor agent 9-amino-[N-(2-dimethylamino)ethyl]acridine-4-carboxamide has been solved to a resolution of 1.6 A using X-ray crystallography. The complex crystallized in space group P6(4) with unit cell dimensions a = b = 30.2 A and c = 39.7 A, alpha = beta = 90 degrees, gamma = 120 degrees. The asymmetric unit contains a single strand of DNA, 1. 5 drug molecules, and 29 water molecules. The final structure has an overall R factor of 19.3%. A drug molecule intercalates between each of the CpG dinucleotide steps with its side chain lying in the major groove, and the protonated dimethylamino group partially occupies positions close to ( approximately 3.0 A) the N7 and O6 atoms of guanine G2. A water molecule forms bridging hydrogen bonds between the 4-carboxamide NH and the phosphate group of the same guanine. Sugar rings adopt the C2'-endo conformation except for cytosine C1 which moves to C3'-endo, thereby preventing steric collision between its C2' methylene group and the intercalated acridine ring. The intercalation cavity is opened by rotations of the main chain torsion angles alpha and gamma at guanines G2 and G6. Intercalation perturbs helix winding throughout the hexanucleotide compared to B-DNA, steps 1 and 2 being unwound by 8 degrees and 12 degrees, respectively, whereas the central TpA step is overwound by 17 degrees. An additional drug molecule, lying with the 2-fold axis in the plane of the acridine ring, is located at the end of each DNA helix, linking it to the next duplex to form a continuously stacked structure. The protonated N,N-dimethylamino group of this "end-stacked" drug hydrogen bonds to the N7 atom of guanine G6. In both drug molecules, the 4-carboxamide group is internally hydrogen bonded to the protonated N-10 atom of the acridine ring. The structure of the intercalated complex enables a rationalization of the known structure-activity relationships for inhibition of topoisomerase II activity, cytotoxicity, and DNA-binding kinetics for 9-aminoacridine-4-carboxamides.     

Visualization of drug-nucleic acid interactions at atomic resolution. VIII. Structures of two ethidium/dinucleoside monophosphate crystalline complexes containing ethidium: cytidylyl(3'-5') guanosine

This paper describes two complexes containing ethidium and the dinucleoside monophosphate, cytidylyl(3'-5')guanosine (CpG). Both crystals are monoclinic, space group P2l, with unit cell dimensions as follows: modification 1: a = 13.64 A, b = 32.16 A, c = 14.93 A, beta = 114.8 degrees and modification 2: a = 13.79 A, b = 31.94 A, c = 15.66 A, beta = 117.5 degrees. Each structure has been solved to atomic resolution and refined by Fourier and least squares methods; the first has been refined to a residual of 0.187 on 1,903 reflections, while the second has been refined to a residual of 0.187 on 1,001 reflections. The asymmetric unit in both structures contains two ethidium molecules and two CpG molecules; the first structure has 30 water molecules (a total of 158 non-hydrogen atoms), while the second structure has 19 water molecules (a total of 147 non-hydrogen atoms). Both structures demonstrate intercalation of ethidium between base-paired CpG dimers. In addition, ethidium molecules stack on either side of the intercalated duplex, being related by a unit cell translation along the a axis. The basic feature of the sugar-phosphate chains accompanying ethidium intercalation in both structures is: C3' endo (3'-5') C2' endo. This mixed sugar-puckering pattern has been observed in all previous studies of ethidium intercalation and is a feature common to other drug-nucleic acid structural studies carried out in our laboratory. We discuss this further in this paper and in the accompanying papers.     

The crystal structure of N4-methylcytosine.guanosine base-pairs in the synthetic hexanucleotide d(CGCGm4CG).

The structure of d(CGCGm4CG) were m4C = N4-methylcytosine has been determined by crystallographic methods. The crystals are multifaced prisms, with orthorhombic space group P2(1)2(1)2(1) and unit cell dimensions of a = 17.98, b = 30.77 and c = 44.75A. The asymmetric unit consists of one duplex of hexanucleotide and 49 waters. The R-factor is 0.189 for 1495 reflections with F > or = sigma(F) to a resolution limit of 1.8A. The double helix has a Z-DNA type structure which appears to be intermediate in structure to the two previously characterised structure types for Z-DNA hexamers. The two m4C.G base-pairs adopt structures that are very similar to those of the equivalent base-pairs in the structure of the native sequence d(CGCGCG) except for the presence of the methyl groups which are trans to the N3 atoms of their parent nucleotides and protrude into the solvent region. The introduction of the modified base-pairs into the d(CGCGCG) duplex appears to have a minimal effect on the overall base-pair morphology of the Z-DNA duplex.     

Visualization of drug-nucleic acid interactions at atomic resolution. X. Structure of a N,N-dimethylproflavine: deoxycytidylyl(3'-5')deoxyguanosine crystalline complex

N,N-dimethylproflavine forms a crystalline complex with deoxycytidylyl(3'-5')deoxyguanosine (d-CpG), space group P2(1)2(1)2, with a = 21.37 A, b = 34.05 A, c = 13.63 A. The structure has been solved to atomic resolution and refined by Fourier and least squares methods to a residual of 0.18 on 2,032 observed reflections. The structure consists of two N,N-dimethylproflavine molecules, two deoxycytidylyl (3'-5')deoxyguanosine molecules and 16 water molecules, a total of 128 nonhydrogen atoms. As with other structures of this type, N,N-dimethylproflavine molecules intercalate between base-paired d-CpG dimers. In addition, dimethylproflavine molecules stack on either side of the intercalated duplex, being related by a unit cell translation along the c axis. Both sugar-phosphate chains demonstrate the mixed sugar puckering geometry: C3' endo (3'-5') C2' endo. This same intercalative geometry has been seen in two other complexes containing N,N-dimethylproflavine and iodoCpG, described in the accompanying paper. Taken together, these studies indicate a common intercalative geometry present in both RNA- and DNA- model systems. Again, N,N-dimethylproflavine behaves as a simple intercalator, intercalating asymmetrically between guanine-cytosine base-pairs. The free amino- group on the intercalated dimethylproflavine molecule does not hydrogen bond directly to the phosphate oxygen. Other aspects of the structure will be presented.     

Crystal structure of the self-complementary 5''-purine start decamer d(GCGCGCGCGC) in the Z-DNA conformation. I.

Alternating self-complementary oligonucleotides starting with a 5'-pyrimidine usually form left-handed Z-DNA; however, with a 5'-purine start sequence they form the right-handed A-DNA. Here we report the crystal structure of the decamer d(GCGCGCGCGC) with a 5'-purine start in the Z-DNA form. The decamer crystallizes in the hexagonal space group P6(5)22, unit cell dimensions a = b = 18.08 and c = 43.10 A, with one of the following four dinucleotide diphosphates in the asymmetric unit: d(pGpC)/d(GpCp)/d(pCpG)/d(CpGp). The molecular replacement method, starting with d(pGpC) of the isomorphous Z-DNA hexamer d(araC-dG)3 without the 2'-OH group of arabinose, was used in the structure analysis. The method gave the solution only after the sugar-phosphate conformation of the GpC step was manipulated. The refinement converged to a final R value of 18.6% for 340 unique reflections in the resolution range 8.0-1.9 A. A result of the sequence alternation is the alternation in the nucleotide conformation; guanosine is C3'-endo, syn, and cytidine is C2'-endo, anti. The CpG step phosphodiester conformation is the same as ZI or ZII, whereas that of the GpC step phosphodiester is "intermediate" in the sense that zeta (O3'-P bond) is the same as ZII but alpha (P-O5' bond) is the same as ZI. The duplexes generated from the dinucleotide asymmetric unit are stacked one on top of the other in the crystal to form an infinite pseudocontinuous helix. This renders it a quasi-polymerlike structure that has assumed the Z-DNA conformation further strengthened by the long inner Z-forming stretch d(CG)4. An interesting feature of the structure is the presence of water strings in both the major and the minor grooves. In the minor groove the cytosine carbonyl oxygen atoms of the GpC and CpG steps are cross-bridged by water molecules that are not themselves hydrogen bonded but are enclosed by the water rings in the mouth of the minor groove. In the major groove three independent water molecules form a zigzagging continuous water string that runs throughout the duplex.     

Anthracycline binding to DNA. High-resolution structure of d(TGTACA) complexed with 4'-epiadriamycin.

Crystallographic methods have been applied to determine the high-resolution structure of the complex formed between the self-complementary oligonucleotide d(TGTACA) and the anthracycline antibiotic 4'-epiadriamycin. The complex crystallises in the tetragonal system, space group P4(1)2(1)2 with a = 2.802 nm and c = 5.293 nm, and an asymmetric unit consisting of a single DNA strand, one drug molecule and 34 solvent molecules. The refinement converged with an R factor of 0.17 for the 2381 reflections with F greater than or equal to 3 sigma F in the resolution range 0.70-0.14 nm. Two asymmetric units associate such that a distorted B-DNA-type hexanucleotide duplex is formed incorporating two drug molecules that are intercalated at the TpG steps. The amino sugar of 4'-epiadriamycin binds in the minor groove of the duplex and displays different interactions from those observed in previously determined structures. Interactions between the hydrophilic groups of the amino sugar and the oligonucleotide are all mediated by solvent molecules. Ultraviolet melting measurements and comparison with other anthracycline-DNA complexes suggest that these indirect interactions have a powerful stabilising effect on the complex.     

The molecular structure of a 4'-epiadriamycin complex with d(TGATCA) at 1.7A resolution: comparison with the structure of 4'-epiadriamycin d(TGTACA) and d(CGATCG) complexes.

The structure of the complex between d(TGATCA) and the anthracycline 4'-epiadriamycin has been determined by crystallographic methods. The crystals are tetragonal, space group P4(1)2(1)2 with unit cell dimensions of a = 28.01, c = 52.95A. The asymmetric unit consists of one strand of hexanucleotide, one molecule of 4'-epiadriamycin and 34 waters. The R-factor is 20.2% for 1694 reflections with F greater than or equal to 2 sigma F to 1.7A. Two asymmetric units associate to generate a duplex complexed with two drug molecules at the d(TpG) steps of the duplex. The chromophore intercalates between these base pairs with the anthracycline amino-sugar positioned in the minor groove. The double helix is a distorted B-DNA type structure. Our structure determination of d(TGATCA) complexed to 4'-epiadriamycin allows for comparison with the previously reported structures of 4'-epiadriamycin bound to d(TGTACA) and to d(CGATCG). The three complexes are similar in gross features and the intercalation geometry is the same irrespective of whether a d(CpG) or d(TpG) sequence is involved. However, the orientation of the amino-sugar displays a dependence on the sequence adjacent to the intercalation site. The flexibility of this amino-sugar may help explain why this class of antibiotics displays a relative insensitivity to base sequence when they bind to DNA.     

Effects of proflavin and photoactivated proflavin on the template function of single-stranded DNA

DNA context-specific effects of the association of proflavin, single-stranded DNA and DNA polymerase on DNA polymerization reactions were examined. Frameshift mutations induced by the presence of proflavin during in vitro DNA replication of a single-stranded DNA template by the Klenow fragment of Escherichia coli DNA polymerase I were sequenced. More than 80% of the frameshifts were one base-pair deletions opposite purine bases that were immediately 3' to pyrimidines. Purines (Pu) that were not adjacent to pyrimidines (Py) were not deletion sites. The remaining deletions were opposite template pyrimidines that were also immediately 3' to another pyrimidine. All pyrimidine site deletions occurred in the context 5' PyPyPu 3'. In additional experiments, the site-specific inhibition of processive DNA polymerization by proflavin was examined. A novel inhibition of polymerization was found opposite all pyrimidines in the template when proflavin-template complexes were exposed to ten seconds of white light. This inhibition of polymerization is reversible. Longer photoactivation led to an altered pattern of DNA sequence-specific inhibition that was not reversible. The role of DNA sequence-specific interactions of proflavin with DNA in proflavin mutagenesis is discussed.     

Reporter molecules as probes of DNA conformation: structure of a crystalline complex containing 2-methyl-4-nitroaniline ethylene dimethylammonium hydrobromide--5-iodocytidylyl (3'-5')guanosine

2-Methyl-4-nitroaniline ethylene dimethylammonium hydrobromide forms a crystalline complex with the self-complementary dinucleoside monophosphate, 5- iodocytidylyl (3'-5')guanosine. The crystals are tetragonal, with a = b = 32.192 A and c = 23.964 A, space group P4(3)2(1)2. The structure has been solved to atomic resolution by Patterson and Fourier methods, and refined by full matrix least squares. 5- Iodocytidylyl (3'-5')guanosine molecules are held together in pairs through Watson-Crick base-pairing, forming an antiparallel duplex structure. Nitroaniline molecules stack above and below guanine-cytosine pairs in this duplex structure. In addition, a third nitroaniline molecule stacks on one of the other two nitroaniline molecules. The asymmetric unit contains two 5- iodocytidylyl (3'-5')guanosine molecules, three nitroaniline molecules, one bromide ion and thirty-one water molecules, a total of 160 atoms. Details of the structure are described.     

Crystal structure analysis of an A-DNA fragment at 1.8 A resolution: d(GCCCGGGC).

Single crystals of the self-complementary octadeoxyribonucleotide d(GCCCGGGC) have been analysed by X-ray diffraction methods at a resolution of 1.8 A. The tetragonal unit cell of space group P4(3)2(1)2 has dimensions of a = 43.25 A and c = 24.61 A and contains eight strands of the oligonucleotide. The structure was refined by standard crystallographic techniques to an R factor of 17.1% using 1359 3 sigma structure factor observations. Two strands of the oligonucleotide are related by the crystallographic dyad axis to form a DNA helix in the A conformation. The d(GCCCGGGC) helix is characterized by a wide open major groove, a near perpendicular orientation of base pairs to the helix axis and an unusually small average helix twist angle of 31.3 degrees indicating a slightly underwound helix with 11.5 base pairs per turn. Extensive cross-strand stacking between guanine bases at the central cytosine-guanine step is made possible by a number of local conformational adjustments including a fully extended sugar-phosphate backbone of the central guanosine nucleotide.     

Visualization of Drug-Nucleic Acid Interactions at Atomic Resolution. IX. Structures of Two N,N-Dimethylproflavine: 5-Iodocytidylyl (3′-5′) Guanosine Crystalline Complexes

Abstract

This paper describes two complexes containing N,N-dimethylproflavine and the dinucleoside monophosphate, 5-iodocytidylyl(3′-5′)guanosine (iodoCpG). The first complex is triclinic, space group PI, with unit cell dimensions a = 11.78 Å, b = 14.55 Å, c = 15.50 Å, a = 89.2°, β = 86.2°, γ = 96.4°. The second complex is monoclinic, space group P2₁, with a = 14.20 Å, b = 19.00 Å, c = 20.73 Å, β = 103.6°. Both structures have been solved to atomic resolution and refined by Fourier and least squares methods. The first structure has been refined anisotropically to a residual of 0.09 on 5,025 observed reflections using block diagonal least squares, while the second structure has been refined isotropically to a residual of 0.13 on 2,888 reflections with full matrix least squares. The asymmetric unit in both structures contains two dimethylproflavine molecules and two iodoCpG molecules; the first structure has 16 water molecules (a total of 134 non-hydrogen atoms), while the second structure has 18 water molecules (a total of 136 non-hydrogen atoms). Both structures demonstrate intercalation of dimethylproflavine between base-paired iodoCpG dimers. In addition, dimethylproflavine molecules stack on either side of the intercalated duplex, being related by a unit cell translation along b and a axes, respectively.

The basic structural feature of the sugar-phosphate chains accompanying dimethylproflavine intercalation in both structures is the mixed sugar puckering pattern: C3′ endo (3′-5′) C2′ endo. This same structural information is again demonstrated in the accompanying paper, which describes a complex containing dimethylproflavine with deoxyribo-CpG.

Similar information has already appeared for other “simple” intercalators such as ethidium, acridine orange, ellipticine, 9-aminoacridine, N-methyl-tetramethylphenanthrolinium and terpyridine platinum. “Complex” intercalators, however, such as proflavine and daunomycin, have given different structural information in model studies. We discuss the possible reasons for these differences in this paper and in the accompanying paper.     

Crystal structures and spectroscopic studies of ternary compounds of Ni(II) with ethylenediamine and 5'GMP and 5'IMP

Two metal complexes [Ni(en)5'GMPH)2(H2O)2] (en).6.5H2O and [Ni(en)(5'IMPH)2(H2O)2].13H2O have been synthesized in the form of suitable crystals for x-ray crystallography (en = ethylenediamine, 5'GMP = guanosine 5'-monophosphate, 5'IMP = inosine 5'-monophosphate). The 5'GMP complex crystallizes in a monoclinic space group P21 (Z = 4) with a = 12.317(2), b = 28.417(4), c = 12.290(2)A, beta (deg) = 89.59(2). The 5'IMP complex is tetragonal, space group P4122 (Z = 4), with a = 12.119(3), b = 12.119(3), c = 28.560(4)A, beta (deg) = 90.0. The crystal structures of both complexes were refined from diffractometer data to conventional R values of 0.073 for the 5'GMP compound (5,284 observed reflections, 1,322 variables) and 0.030 for the 5'-IMP compound (1,529 observed reflections, 296 variables). In both structures, the Ni(II) is surrounded by two water molecules, one chelate ethylenediamine, and two nucleotide molecules. The synthesis was carried out from Ni(en)2Cl2.0.5H2O and the nucleotide in water medium. The dimer structure of the initial complex is broken, and one ethylenediamine is substituted by two molecules of the nucleotide with the N(7) of the purine ring in cis-position. Differences between both structures are largely due to retention in the structure or loss of the en molecule substituted and to the intermolecular hydrogen bonds of the en molecule coordinated. A third complex of composition [Ni(en)(5'IMPH)2(H2O)2] (en).6H2O similar to the 5'GMP complex has been obtained in the form of blue crystals, but unfortunately its crystal structure failed to be refined. This complex is isostructural with the monoclinic one.