Effects of Substituents on the Binding Energy in Hydrogen-bonded Complexes Containing Adenine and Thymine†

doi:10.7503/cjcu20130707

Abstract

Abstract:

The optimal structures and binding energies of seventeen substitutional thymine and adenine hydrogen-bonded complexes were obtained theoretically and the effects of substituents on the binding energies were explored. The calculation results show that the interaction between trifluridine and adenine is stronger than that between thymine and adenine. This conclusion is in agreement with the fact that the association of trifluridine and adenine has precedence over the association of thymine and adenine. Compared with CF₃, three stronger electron withdrawing groups(SO₃H, CN and NO₂) can increase the binding energy between thymine and adenine, suggesting that the thymine substituted by these three groups may also provide a potential anticancer application. Atoms in molecules theory and the natural bond orbital analysis indicate that N—H…N hydrogen bon-ding is the strongest, N—H…O=C is stronger, while C—H…O=C is the weakest. Atoms in molecules theory and the natural bond orbital analysis also indicate that the orbital overlap interactions play a signi-ficant role in these hydrogen bonds.

Key words: Trifluridine, Thymine, Adenine, Substituent effect, Binding energy, Hydrogen bond

CLC Number:

O641

TrendMD:

LIU Peng, LI Shushi, WANG Changsheng. Effects of Substituents on the Binding Energy in Hydrogen-bonded Complexes Containing Adenine and Thymine^†[J]. Chem. J. Chinese Universities, 2014, 35(1): 154.

Figures/Tables 6

Scheme 1 Molecular structure of trifluridine

Scheme 2 Model structure of 17 hydrogen-bonded complexes R=H, CH3, CF3, NHCH3, NH2, OCH3, Et, BH2, Br, Cl, CCl3, CHO, COOH, COMe, CN, SO3H, NO2

Fig.1 Optimal geometries and bonding energies of 17 hydrogen-bonded complexesBond lengths are in nm and bond angles are in degree.

Table 1 Electron densities(a.u.) at the hydrogen bond critical points and the binding energies(kJ/mol)

R	ρ_c(C—H…O=C)	ρ_c(N…H—N)	ρ_c(N—H…O=C)	∑ρ_c	E_b
NHCH₃	0.0046	0.0409	0.0269	0.0724	-58.55
NH₂	0.0047	0.0413	0.0267	0.0726	-58.97
Et	0.0044	0.0405	0.0277	0.0726	-59.30
CH₃	0.0044	0.0407	0.0277	0.0728	-59.39
OCH₃	0.0048	0.0412	0.0270	0.0730	-59.53
H	0.0044	0.0409	0.0279	0.0732	-59.74
COMe	0.0049	0.0419	0.0263	0.0731	-60.25
BH₂	0.0044	0.0414	0.0274	0.0732	-60.84
Cl	0.0049	0.0428	0.0264	0.0741	-61.43
CHO	0.0046	0.0427	0.0264	0.0737	-61.49
Br	0.0050	0.0430	0.0263	0.0743	-61.49
CCl₃	0.0051	0.0436	0.0258	0.0745	-62.22
COOH	0.0054	0.0449	0.0241	0.0744	-62.23
CF₃	0.0048	0.0432	0.0260	0.0740	-62.39
SO₃H	0.0058	0.0471	0.0233	0.0762	-63.17
NO₂	0.0054	0.0443	0.0253	0.0750	-63.52
CN	0.0048	0.0443	0.0266	0.0757	-63.58

Table 2 Second-order stabilization energies(Eij, kJ/mol) of the 17 hydrogen-bonded complexes obtained at the B3LYP/6-311G(3df,2p) level and the binding energies(Eb, kJ/mol) obtained at the CP-corrected MP2/6-311++G(3df,2p) level

R	$E ij (nO → σ * H — C)$	$E ij (nN → σ * H — N)$	$E ij (nO → σ * H — N)$	E_ij	E_b	ΔE_ij	ΔE_b
NHCH₃	1.00	92.84	41.67	135.52	-58.55	-3.51	-1.19
NH₂	1.05	94.35	41.25	136.65	-58.97	-2.38	-0.77
Et	0.75	91.63	44.56	136.94	-59.30	-2.09	-0.43
CH₃	0.75	92.34	44.69	137.78	-59.39	-1.26	-0.35
OCH₃	1.09	94.47	42.09	137.65	-59.53	-1.38	-0.21
H	0.71	93.30	45.02	139.03	-59.74	0	0
COMe	1.13	97.78	40.12	139.03	-60.25	0	0.51
BH₂	0.75	95.86	43.35	139.95	-60.84	0.92	1.10
Cl	1.13	100.67	40.58	142.38	-61.43	3.35	1.69
CHO	0.79	101.13	40.25	142.17	-61.49	3.14	1.75
Br	1.17	101.50	40.21	142.88	-61.49	3.85	1.75
CCl₃	1.21	104.31	38.49	144.01	-62.22	4.98	2.48
COOH	1.30	110.12	30.71	142.13	-62.23	3.10	2.49
CF₃	1.09	102.63	39.46	143.18	-62.39	4.14	2.65
SO₃H	1.46	118.62	29.37	149.45	-63.17	10.42	3.43
NO₂	1.30	107.49	37.61	146.40	-63.52	7.36	3.78
CN	1.05	107.57	40.58	149.20	-63.58	10.17	3.84

R	$E ij (nO → σ * H — C)$	$E ij (nN → σ * H — N)$	$E ij (nO → σ * H — N)$	E_ij	E_b	ΔE_ij	ΔE_b
NHCH₃	1.00	92.84	41.67	135.52	-58.55	-3.51	-1.19
NH₂	1.05	94.35	41.25	136.65	-58.97	-2.38	-0.77
Et	0.75	91.63	44.56	136.94	-59.30	-2.09	-0.43
CH₃	0.75	92.34	44.69	137.78	-59.39	-1.26	-0.35
OCH₃	1.09	94.47	42.09	137.65	-59.53	-1.38	-0.21
H	0.71	93.30	45.02	139.03	-59.74	0	0
COMe	1.13	97.78	40.12	139.03	-60.25	0	0.51
BH₂	0.75	95.86	43.35	139.95	-60.84	0.92	1.10
Cl	1.13	100.67	40.58	142.38	-61.43	3.35	1.69
CHO	0.79	101.13	40.25	142.17	-61.49	3.14	1.75
Br	1.17	101.50	40.21	142.88	-61.49	3.85	1.75
CCl₃	1.21	104.31	38.49	144.01	-62.22	4.98	2.48
COOH	1.30	110.12	30.71	142.13	-62.23	3.10	2.49
CF₃	1.09	102.63	39.46	143.18	-62.39	4.14	2.65
SO₃H	1.46	118.62	29.37	149.45	-63.17	10.42	3.43
NO₂	1.30	107.49	37.61	146.40	-63.52	7.36	3.78
CN	1.05	107.57	40.58	149.20	-63.58	10.17	3.84

Fig.2 Correlation between the electron densities at the hydrogen bond critical points(∑ρc) and the binding energies(A) and correlation between the second-order stabilization energies ΔEij and the binding energies relative to R=H(B)

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