Theoretical study by DFT and TD–DFT of NLO-active push–pull molecules composed of conjugated bridges based on cyclic rings: Titanol, Ferrol, Nickelol and Zinkol

Article

Author: Hedidi, Madani ; Laib, Assia ; Zouaoui-Rabah, Mourad ; Elhorri, Abdelkader M ; Mahdjoub-Araibi, Hicham ; Zenati, Mohammed

CONTEXTThis research is based on the theoretical study of seven push-pull molecules composed of conjugated bridges based on two different organometallic rings, these bridges are linked at their ends by acceptor groups (-NO₂) and donor groups (-N(CH₃)₂) on the α position of the rings mentioned above. The location of the donor and acceptor groups revealed that the addition of the acceptor groups near the rings (Titanol, Ferrol and Nickelol) improves the NLO response in comparison with the grafting of these groups on the Zinkol ring and also influences the positioning of the π electrons at the level of the chromophores studied. The molecule 2B gave the highest values of static first hyperpolarisabilitiy (β_tot) and static second hyperpolarisabilitiy (γ_av), knowing that: β_tot (2B) = 135.79 * 10^-30 esu and γ_av (2B) = 135.79 * 10^-35 esu. The highest values of dynamic first __-mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"-__ β ‖ λ - 2 ω ; ω , ω and second __-mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"-__ γ ‖ λ - 2 ω ; ω , ω , 0 hyperpolarisabilities are assigned to the molecule 1C with the following values: __-mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"-__ γ ‖ λ - 2 ω ; ω , ω , 0 =1,218,310.00 * 10^-30 esu and __-mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"-__ γ ‖ λ - 2 ω ; ω , ω , 0 =1,324,520,000 * 10^-35 esu. The metal Zn is considered as an acceptor group and the remaining metals (Ti, Fe and Ni) are considered as donor groups. The specific solvents for the seven molecules are water, ethanol and acetonitrile. The maximum wavelengths recorded for all molecules in combination with all solvents are in the range of 421.39 to 765.28 nm. λ METHOD: The calculations were performed using Gaussian 16 software to perform DFT calculations with B3LYP functional. The LanL2DZ basis-set was used for transition metals, while the 6-31 + + G(d,p) basis-set was used for nonmetal atoms. The functionals used are: CAM-B3LYP, LC-wPBE, LC-BLYP, M11, wB97X, M08-HX, M06-2X, MN12SX, MN15, and M06HF. The basis-sets used are: 6-31G(d,p), 6-31 + + G(d,p), cc-pVDZ, aug-cc-pVDZ, 6-311G(d,p), 6-311 + + G(d,p), cc-pVTZ, and aug-cc-pVTZ. The Natural Bond Orbital (NBO) calculations are performed by the NBO program incorporated by default in the Gaussian 16 program. The solvation models studied are the CPCM model (conductor polarizable continuum model) and the SMD model (Solvation Model Density). Excited states calculations are calculated by the time-dependent DFT method (TD-DFT).

01 Mar 2025·Journal of Molecular Modeling

In-depth theoretical study on the impact of transition metals incorporation into the cavities of porphyrins considered conjugated bridges in NLO-active push–pull molecules: analysis by DFT, NBO, and TD–DFT

Article

Author: Laib, Assia ; Mahdjoub-Araibi, Hicham ; Zenati, Mahammed ; Elhorri, Abdelkader M ; Zouaoui-Rabah, Mourad ; Hedidi, Madani

CONTEXTThis research focuses on the theoretical study of six push-pull molecules composed of conjugated bridges based on porphyrin and metalloporphyrins where the metals used are Fe(II), Co(II), Ni(II), Cu(II), and Zn(II); these bridges are linked at their ends by acceptor groups (-NO₂) and donors (-N(CH₃)₂) at the meso positions of the cycles mentioned before. The CAM-B3LYP, M08HX, and MN15 functionals tend to describe well the systems studied in non-linear optics NLO in addition to the use of the basis set 6-31 + + G(d,p) which is considered to be the adequate and least expensive basis set. The highest values of the first static hyperpolarizabilities (β_tot) are assigned to the two molecules 2A and 3A; the corresponding values are as follows: β_tot (2A) = 46.43 * 10^-30 esu and β_tot (3A) = 46.30 * 10^-30 esu. The highest value of the second static hyperpolarizability (γ_av) is assigned to the molecule 1A5 with a value of 9.49 * 10^-35 esu. The highest values of the first dynamic hyperpolarizabilities ( __-mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"-__ β | | λ ( - 2 ω ; ω , ω ) ) and second dynamics hyperpolarizabilities ( __-mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"-__ γ | | λ ( - 2 ω ; ω , ω , 0 ) ) are attributed to the molecule 2A; the corresponding values are as follows: __-mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"-__ β | | λ ( - 2 ω ; ω , ω ) ) (2A) = 8229.88 * 10^-30 esu and __-mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"-__ γ | | λ ( - 2 ω ; ω , ω , 0 ) (2A) = - 10,943.10 * 10^-35 esu. The molecules 1A2 and 1A5 based on the metals Co(II) and Zn(II), respectively, are the most profitable in second- and third-order dynamic NLOs. The specific solvents for the six molecules are acetone, acetonitrile, and dichloromethane. The maximum wavelengths recorded for all molecules in vacuum and in combination with all solvents are in the range 355.75 to 397.15 nm and absorb in the UV transparency.METHODAll calculations were performed with the Gaussian 16 program. The dispersion functional B3LYP-D3 is used for optimizations. Electronic parameters were calculated using the following functionals: CAM-B3LYP, LC-wPBE, LC-BLYP, M11, wB97X, M08-HX, M06-2X, MN12SX, and MN15. The basis set studied for the whole manuscript is 6-31 + + G(d,p) for non-metallic atoms and LanL2DZ for transition metals. Other basis sets studied include 6-31G(d,p), 6-31 + + G(d,p), cc-pVDZ, AUG-cc-pVDZ, 6-311G(d,p), 6-311 + + G(d,p), cc-pVTZ, and AUG-cc-pVTZ. The natural bond orbital (NBO) method was also considered. The implicit solvation models studied are solvation models based on density (SMD) and conductor polarizable continuum model (C-PCM). The time-dependent density functional (TD-DFT) approach was also studied.

01 Nov 2024·European Journal of Medicinal Chemistry

Design, synthesis and biological evaluation of N-salicyloyl tryptamine derivatives as multifunctional neuroprotectants for the treatment of ischemic stroke

Article

Author: Chen, Yaxin ; Tian, Ying ; Wu, Genping ; Li, Bo ; Wei, Xiuzhen ; Wang, Zhen ; Hu, Zecheng ; Su, Jianhui ; Zhuo, Linsheng ; Zhao, Yuting ; Peng, Xue ; Peng, Yan

Ischemic stroke (IS) is a disease of high death and disability worldwide with few medications in clinical treatment. Neuroinflammation and oxidative stress are considered as crucial factors in the progression of IS. In our previous studies, N-salicyloyl tryptamine derivative (NST) L7 exhibited promising anti-inflammatory properties and is considered a potential clinical therapy for IS but had limited antioxidant capacity. Here, we have designed, synthesized, and biologically evaluated 30 novel NSTs for their neuroprotective effects against cerebral ischemia-reperfusion (CI/R) injury. To identify a multifunctional neuroprotectant with enhanced antioxidant and anti-inflammatory capacity, as well as an effective therapeutic agent for CI/R damage. Among them, M11 exhibited synergistic highly anti-oxidant, anti-inflammatory, anti-ferroptosis, and anti-apoptosis effects and surpassed the parent compound L7. Further studies demonstrated that the synergistic and efficient neuroprotective role of M11 was mainly achieved by activating Nrf2 and stimulating its downstream target HO-1/GCLC/NQO1/GPX4. In addition, M11 possessed good blood-brain barrier permeability. Moreover, M11 effectively reduced cerebral infarct volume and improved neurological deficits in MCAO/R mice. Its hydrochloride form, M11·HCl, exhibited better pharmacokinetic properties, high safety, and a significant reduction in infarct volume, which is comparable to Edaravone. In conclusion, our findings suggested that M11 capable of activating Nrf2, could represent a promising candidate agent for IS.

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Indication	Highest Phase	Country/Location	Organization	Date
Muscular Diseases	Preclinical	United States	Juvena Therapeutics, Inc.Startup	14 Nov 2023

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