取代基对腺嘌呤与胸腺嘧啶氢键复合物体系结合能的影响

doi:10.7503/cjcu20130707

摘要/Abstract

摘要：

优化得到了17个取代胸腺嘧啶与腺嘌呤形成的氢键复合物的结构, 并计算了这些复合物的结合能, 探讨了胸腺嘧啶上不同取代基对结合能的影响. 结果表明, CF₃取代的胸腺嘧啶与腺嘌呤间的结合能大于胸腺嘧啶与腺嘌呤间的结合能, 这可能是屈氟尿苷具有阻止病毒及肿瘤扩散功能的原因所在. SO₃H, CN和NO₂取代的胸腺嘧啶与腺嘌呤间具有更大的结合能, 表明这3个基团取代的胸腺嘧啶也可能具有潜在的抗肿瘤作用. 分子中原子理论与自然键轨道分析表明, 在所有体系中, 氢键N—H…N最强, N—H…O=C次之, C—H…O=C最弱, 轨道作用在氢键作用中占有重要地位.

关键词: 屈氟尿苷, 胸腺嘧啶, 腺嘌呤, 取代基效应, 结合能, 氢键

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

中图分类号:

O641

TrendMD:

刘朋, 李书实, 王长生. 取代基对腺嘌呤与胸腺嘧啶氢键复合物体系结合能的影响. 高等学校化学学报, 2014, 35(1): 154.

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

图/表 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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