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Role of pH in the stability of cytosine-cytosine mismatch and canonical AT and GC base pairs mediated with silver ion: a DFT study

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Abstract

Metallo-nucleic acids have been investigated for their applications in the field of nanodevices and genetic expansion. The cytosine-Ag+-cytosine mismatch base pair interactions and their stability in nucleic acids have attracted the attention of chemists. We report a systematic study of canonical, mismatch, Ag+ mediated system with CC, AT, and GC base pairs computationally. The stability of such mismatch base pairs is dependent on the pH range ~ 5 to 9 and the duplexes beyond this range are unstable. The DFT calculations performed with the model DNA duplexes comprising of such mismatch pairs reveal the stability trend while varying the pH conditions. The stability of canonical Watson–Crick ATGC base pairs was compared with the CCAT and CCGC mismatch base pairs and the calculated results at B3LYP-D3/6-31G(d) level of theory in the aqueous phase suggest that the base stacking and hydrogen bonding are well maintained in the former case, however, the larger perturbations in the geometry are observed with the mispair and relatively unstable. The calculated binding energy B3LYP-D3/6-31G(d) level of theory of ATGC is energetically more stable (~ 20 kcal/mol) than the mismatch base pairs. The Ag+ mediated mismatch base pairs i.e., C_CAT and C_CGC examined at the same level of theory suggest that the CC mismatch base pairs complexed with proper alignment to the Ag+ ion and the AT and GC bases maintained the hydrogen bonding interactions. The relative binding energies have been calculated with 6–311 + G(d,p) basis set using B3LYP-D3 and wb97xd DFT functionals in the study. The mismatched base pair duplex systems i.e., C_CAT and C_CGC are structurally similar to the canonical Watson–Crick base pairs and energetically stable by ~ 40 and ~ 50 kcal/mol compared to the canonical ATGC base pairs. The experimental report on the thermal transition profile in 5’-(A)10C(A)10–3’ and 5’ (T)10C(T)10–3’ duplexes showed remarkable stability and corroborate the calculated results (Ono et al. in Chem Commun 4825−4827, 2008). The stability of Ag+ mediated mismatch bases at the higher pH 9 was also examined and the nucleobases such as guanine and thymine would be deprotonated under this condition. The calculated results suggest that the CCA_T and CCG_C duplexes are largely distorted with the complexation of Ag+ with the AT and GC base pairs and would in turn denature the duplex. The AIM analysis performed at B3LYP-D3/6-31G(d) level of theory for all the studied Ag+ mediated complexes reveals that the Ag+ interaction with the corresponding nucleobases was electrostatic in nature. The role of pH in governing the stability of C–Ag+-C complex formation in mismatch base nucleic acids is crucial for their application of genetic expansion and nucleic acid-based nanodevices.

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Acknowledgements

S.B is thankful to the Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, Uttar Pradesh, India, for his Ph.D. registration. S.B acknowledges CSIR, New Delhi, India for CSIR-SRF fellowship. We thank the reviewers for their valuable comments and suggestions that have helped us to improve the paper. CSIR-CSMCRI 145/2021 registration number.

Funding

S.B. and B.G were financially supported by the Department of biotechnology (DBT), New Delhi (Grant no. BT/PR12730/BID/7/523/2015), and Department of Science & Technology (DST).

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Authors and Affiliations

  1. Computation and Simulation Unit (Analytical and Environmental Science Division and Centralized Instrument Facility), CSIR-Central Salt and Marine Chemicals Research Institute, Bhavnagar, 364 002, Gujarat, India

    Surjit Bhai & Bishwajit Ganguly

  2. Academy of Scientific and Innovative Research (AcSIR), Uttar Pradesh, Ghaziabad, 201002, India

    Surjit Bhai & Bishwajit Ganguly

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Bhai, S., Ganguly, B. Role of pH in the stability of cytosine-cytosine mismatch and canonical AT and GC base pairs mediated with silver ion: a DFT study. Struct Chem 33, 35–47 (2022). https://doi.org/10.1007/s11224-021-01814-x

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