Solvent effect on the conformation of the Hoechst 33258 agent

Sapse, Anne‐Marie; Mezei, Mihaly; Karakhanov, Iuli; Jain, Duli C.

doi:10.1016/s0166-1280(96)04861-0

Cited by 6 publications

(4 citation statements)

References 20 publications

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“…This conformational behavior is similar to that found for other aromatic compounds constituted by two rings attached by a single bond [38,39]. On the other hand, the present results are in poor agreement with those reported at the HF/3-21G and HF/STO-3G levels [7,8], which tend to overestimate the stability of the planar conformations. However, this semiempirical method overestimated the deviation of the inter-ring dihedral angles a and b with respect the planarity by about 10°.…”

Section: Conformational Preferences Of the Aromatic Fragments For Hoesupporting

confidence: 78%

“…Comparison of our results with those previously reported indicate a qualitative agreement with those obtained at the AM1 semiempirical level [6] whereas no agreement is found with those computed at the HF/3-21G and HF/STO-3G levels [7,8]. Comparison of our results with those previously reported indicate a qualitative agreement with those obtained at the AM1 semiempirical level [6] whereas no agreement is found with those computed at the HF/3-21G and HF/STO-3G levels [7,8].…”

Section: Discussionsupporting

confidence: 66%

“…It is an N-methyl piperazine derivative with two benzimidazole groups and one phenol group. More recently, Sapse et al [8] studied the eect of the solvent on the conformation of Hoechst 33258 using the SM1a mode [27]. The results indicated that Hoechst 33258 does not adopt a planar conformation, but is similar to those observed in DNA complexes by X-ray crystallography.…”

Section: Introductionmentioning

confidence: 98%

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An ab initio study of the conformational preferences of Hoechst 33258 in gas-phase and aqueous solution environments

Alemán¹

1998

Theoretical Chemistry Accounts: Theory, Computation, and Modeli

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A quantum mechanical study of the conformational preferences of Hoechst 33258, a synthetic minor groove-binding drug, has been performed in both gas-phase and aqueous solution. Gas-phase calculations were performed at the HF/6-31G(d) and MP2/6-31G(d) levels of theory, whereas calculations in the aqueous solution phase were performed using the PCM model with the 6-31G(d) basis set. The molecule was divided into three fragments, which were submitted to a systematic and detailed conformational study. The results clearly indicate that Hoechst 33258 does not adopt a planar conformation in either the gas-phase or aqueous solution. Thus, a folded conformation is not induced by binding of the molecule to DNA, but is an intrinsic property of the compound.

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Section: Conformational Preferences Of the Aromatic Fragments For Hoesupporting

confidence: 78%

Section: Discussionsupporting

confidence: 66%

Section: Introductionmentioning

confidence: 98%

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An ab initio study of the conformational preferences of Hoechst 33258 in gas-phase and aqueous solution environments

Alemán¹

1998

Theoretical Chemistry Accounts: Theory, Computation, and Modeli

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“…Hoechst 33258, 2′-(4-hydroxyphenyl)-5-[5-(4-methylpiperazine-1-yl)benzimidazo-2-yl]bezimidazole, is a synthetic bis-(benzimidazole) derivative developed by the Hoechst Pharmaceutical Co. 1 Since the early 1970s, various research work on this compound has been done. Hoechst 33258 has been widely used as a fluorescent DNA stain.…”

Section: Introductionmentioning

confidence: 99%

Multiple Binding Modes for Dicationic Hoechst 33258 to DNA

Guan

Shi

et al. 2007

J. Phys. Chem. B

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The binding of dicationic Hoechst 33258 (ligand) to DNA was characterized by means of the fluorescence spectra, fluorescence intensity titration, time-resolved fluorescence decay, light scattering, circular dichroism, and fluorescence thermal denaturation measurements, and two binding modes were distinguished by the experimental results. Type 1 binding has the stoichiometry of one ligand to more than 12 base pairs, and it is defined as quasi-minor groove binding which has the typical prolonged fluorescence lifetime of about 4.4 ns. In type 1 binding, planar conformation of the ligand is favorable. Type 2 binding with phosphate to ligand ratio (P/L) < 2.5 has the stoichiometry of one ligand to two phosphates. It is defined as a highly dense and orderly stacked binding with DNA backbone as the template. Electrostatic interactions between doubly protonated ligands and negatively charged DNA backbone play a predominant role in the type 2 binding mode. The characteristics of this type of binding result in a twisted conformation of the ligand that has a fluorescence lifetime of less than 1 ns. The results also indicate that the binding is in a cooperative manner primarily by stacking of the aromatic rings of the neighboring ligands. Type 1 binding is only observed for double-stranded DNA (dsDNA) with affinity constant of 1.83 x 10(7) M-1. In the type 2 binding mode, the binding affinity constants are 4.9 x 10(6) and 4.3 x 10(6) M-1 for dsDNA and single-stranded DNA (ssDNA), respectively. The type 2 binding is base pair independent while the type 1 binding is base pair related. The experiments described in this paper revealed that the dication bindings are different from the monocation bindings reported by previous study. The dication binding leads to stronger aggregation at low ligand concentration and results in orderly arrangements of the ligands along DNA chains. Furthermore the dication binding is demonstrated to be beneficial for enhancing the DNA's stability.

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Ab Initioand DFT Studies on the Structure, Infrared Spectrum, and Thermodynamic Properties of Hoechst 33258

Wang

Qiu

et al. 2005

Jnl Chinese Chemical Soc

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Ab initio and DFT(B3LYP) levels of theory, with basis sets of 3–21G, 6–31G*, and LanL2DZ, have been applied to the specific DNA binder Hoechst 33258. All calculations lead to a structure with two benzimidazole groups and one phenyl group being coplanar. Atoms H33 and H37 bear large positive charges, and the distance between the two atoms is about 5 Å, which allows the molecule interacting with the negative sites of neighboring bases in the DNA helix and thus facilitates Hoechst 33258 to gravitate on AT‐rich regions in the minor groove of DNA, owing to the deeper negative potential in such sequences. The most stable conformer corresponds to the dihedral angles of ca. 0° for ϕ1‐2‐14‐15 and ϕ27‐26‐5‐4, and 180° for ϕ20‐19‐11‐12. This fact provides clear evidence that Hoechst 33258 has an arc‐like shape with coplanar aromatic rings. Both the HOMO and the LUMO are made up of the Pz orbitals of the non‐hydrogen atoms in two benzimidazole groups and one phenyl group. On going from the ground state to the first singlet excited state, the lengths of the single bonds between the aromatic rings decrease, and the aromatic rings are more conjugated with each other in the excited state. The heat of formation (ΔHf) of Hoechst 33258, evaluated from the isodesmic reaction, is 406.32 kJ/mol at the B3LYP/6–31G* level.

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Solvent effect on the conformation of the Hoechst 33258 agent

Cited by 6 publications

References 20 publications

An ab initio study of the conformational preferences of Hoechst 33258 in gas-phase and aqueous solution environments

An ab initio study of the conformational preferences of Hoechst 33258 in gas-phase and aqueous solution environments

Multiple Binding Modes for Dicationic Hoechst 33258 to DNA

Ab Initioand DFT Studies on the Structure, Infrared Spectrum, and Thermodynamic Properties of Hoechst 33258

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