Interplay between occurrence frequencies of charged and neutral base pairs in small-molecule crystals

Abstract We used the high resolution and accuracy of the Cambridge Structural Database (CSD) to provide detailed information regarding base pairing interactions of selected nucleobases. We searched for base pairs in which nucleobases interact with each other through two or more hydrogen bonds and form more or less planar structures. The investigated compounds were either free forms or derivatives of adenine, guanine, hypoxanthine, thymine, uracil and cytosine. We divided our findings into categories including types of pairs, protonation patterns and whether they are formed by free bases or substituted ones. We found base pair types that are exclusive to small molecule crystal structures, some that can be found only in RNA containing crystal structures and many that are native to both environments. With a few exceptions, nucleobase protonation generally followed a standard pattern governed by pKa values. The lengths of hydrogen bonds did not depend on whether the nucleobases forming a base pair were charged or not. The reasons why particular nucleobases formed base pairs in a certain way varied significantly.

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Crystallographic evidence of Watson–Crick connectivity in the base pair of anionic adenine with thymine

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2008379117 ◽

2020 ◽

Vol 117 (31) ◽

pp. 18224-18230

Author(s):

Manish Kumar Mishra ◽

Steven P. Kelley ◽

Volodymyr Smetana ◽

David A. Dixon ◽

Ashley S. McNeill ◽

...

Keyword(s):

Gas Phase ◽

Base Pair ◽

Phase Reaction ◽

Base Pairs ◽

Gas Phase Reaction ◽

Neutral Base ◽

The Stability ◽

Structure Calculations ◽

Insight Into ◽

Stable Formation

Utilizing an ionic liquid strategy, we report crystal structures of salts of free anionic nucleobases and base pairs previously studied only computationally and in the gas phase. Reaction of tetrabutylammonium ([N4444]+) or tetrabutylphosphonium ([P4444]+) hydroxide with adenine (HAd) and thymine (HThy) led to hydrated salts of deprotonated adenine, [N4444][Ad]·2H2O, and thymine, [P4444][Thy]·2H2O, as well as the double salt cocrystal, [P4444]2[Ad][Thy]·3H2O·2HThy. The cocrystal includes the anionic [Ad−(HThy)] base pair which is a stable formation in the solid state that has previously not even been suggested. It exhibits Watson–Crick connectivity as found in DNA but which is unusual for the free neutral base pairs. The stability of the observed anionic bases and their supramolecular formations and hydrates has also been examined by electronic structure calculations, contributing to more insight into how base pairs can bind when a proton is removed and highlighting mechanisms of stabilization or chemical transformation in the DNA chains.

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Komplexe von Desoxyribonucleinsäure mit Azoverbindungen und Diazinen, I DNA und 2-Amio-benzo[c]cinnolin / Azo Compound and Diazine Complexes of Desoxyribonucleic Acid, I DNA and 2-Amino-benzo[c]cinnoline

Zeitschrift für Naturforschung C ◽

10.1515/znc-1975-1-207 ◽

1975 ◽

Vol 30 (1-2) ◽

pp. 29-32

Author(s):

Hermann Rau ◽

Gisela Schuster

Keyword(s):

Charge Transfer ◽

Complex Formation ◽

Small Molecule ◽

Salt Concentration ◽

Deoxyribonucleic Acid ◽

Desoxyribonucleic Acid ◽

Base Pairs ◽

Azo Compound ◽

Complex Constant

Abstract Complex formation of deoxyribonucleic acid and 2-amino-benzo [c] cinnoline is demonstrated by spectroscopic means. The small molecule though uncharged seems to intercalate between the base pairs of the deoxyribonucleic acid like the acridines. The complex constant, however, is smaller by about two orders of magnitude. The influence of salt concentration and temperature on the equilibrium is investigated. The involvement of charge-transfer contribution is suggested.

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Selective Small Molecule Recognition of RNA Base Pairs

ACS Combinatorial Science ◽

10.1021/acscombsci.8b00049 ◽

2018 ◽

Vol 20 (8) ◽

pp. 482-491 ◽

Cited By ~ 14

Author(s):

Hafeez S. Haniff ◽

Amanda Graves ◽

Matthew D. Disney

Keyword(s):

Small Molecule ◽

Base Pairs ◽

Molecule Recognition

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Importance of Model Size in Quantum Mechanical Studies of DNA Intercalation

10.26434/chemrxiv.9936473.v1 ◽

2019 ◽

Author(s):

Drew P. Harding ◽

Laura J. Kingsley ◽

Glen Spraggon ◽

Steven Wheeler

Keyword(s):

Binding Site ◽

Small Molecule ◽

Computational Cost ◽

Dna Intercalation ◽

Interaction Energies ◽

Base Pairs ◽

Dna Base ◽

Dna Base Pairs ◽

Model Size ◽

Reliable Interaction

There is currently a dearth of effective computational tools to design nucleobase-targeting small molecules and molecular mechanics force-fields for nucleobases lag behind their protein-focused counterparts. While quantum chemical methods can provide reliable interaction energies for small molecule-nucleobase interactions, these come at a steep computational cost. As a first step toward refining available tools for predicting small molecule-nucleobase interactions, we assessed the convergence of DFT-computed interaction energies with increasing binding site model size. We find that while accurate intercalator interaction energies can be derived from binding site models featuring only the flanking nucleotides for uncharged intercalators that bind parallel to the DNA base pairs, errors remain significant even when including distant nucleotides for intercalators that are charged, exhibit groove-binding tails that engage in non-covalent interactions with distant nucleotides, or that bind perpendicular to the DNA base pairs. Consequently, binding site models that include at least three adjacent nucleotides are required to consistently predict converged binding energies. The computationally inexpensive HF-3c method is shown to provide reliable interaction energies and can be routinely applied to such large models.<br>

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Importance of Model Size in Quantum Mechanical Studies of DNA Intercalation

10.26434/chemrxiv.9936473 ◽

2019 ◽

Author(s):

Drew P. Harding ◽

Laura J. Kingsley ◽

Glen Spraggon ◽

Steven Wheeler

Keyword(s):

Binding Site ◽

Small Molecule ◽

Computational Cost ◽

Dna Intercalation ◽

Interaction Energies ◽

Base Pairs ◽

Dna Base ◽

Dna Base Pairs ◽

Model Size ◽

Reliable Interaction

There is currently a dearth of effective computational tools to design nucleobase-targeting small molecules and molecular mechanics force-fields for nucleobases lag behind their protein-focused counterparts. While quantum chemical methods can provide reliable interaction energies for small molecule-nucleobase interactions, these come at a steep computational cost. As a first step toward refining available tools for predicting small molecule-nucleobase interactions, we assessed the convergence of DFT-computed interaction energies with increasing binding site model size. We find that while accurate intercalator interaction energies can be derived from binding site models featuring only the flanking nucleotides for uncharged intercalators that bind parallel to the DNA base pairs, errors remain significant even when including distant nucleotides for intercalators that are charged, exhibit groove-binding tails that engage in non-covalent interactions with distant nucleotides, or that bind perpendicular to the DNA base pairs. Consequently, binding site models that include at least three adjacent nucleotides are required to consistently predict converged binding energies. The computationally inexpensive HF-3c method is shown to provide reliable interaction energies and can be routinely applied to such large models.<br>

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A privileged ternary blend enabling non-fullerene organic photovoltaics with over 14% efficiency

Journal of Materials Chemistry C ◽

10.1039/d0tc02778b ◽

2020 ◽

Vol 8 (43) ◽

pp. 15135-15141

Author(s):

Jing Yan ◽

Yuan-Qiu-Qiang Yi ◽

Jianqi Zhang ◽

Huanran Feng ◽

Yanfeng Ma ◽

...

Keyword(s):

Small Molecule ◽

Organic Photovoltaics ◽

Power Conversion ◽

Ternary Blend ◽

Conversion Efficiencies

Two non-fullerene small molecule acceptors, NT-4F and NT-4Cl, were designed and synthesized. Power conversion efficiencies of 11.44% and 14.55% were achieved for NT-4Cl-based binary and ternary devices, respectively.

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