Focusing our DFT calculations on the carboxylic acid drugs such as ibuprofen drug (IBF), it has been concluded that the anions of these types of drugs have the spontaneous electron donor character to all the carcinogenic cells of electron deficiency in their nuclei. Due to the spontaneity of electron transfer of anions, it has been found clinically that ibuprofen drug cures cancers of colon, protostate, lung and breast. The breast cancer treatment of Matthew Gdovin group in two hours by injection of ethanolic solution of nitrobenzaldehyde in the breast tumor in presence of uv-irradiation has been studied from TD-DFT point of view; the excited states of these molecules in presence of uv-irradiation act as electron donors to the cancerous cells to compensate the electron deficiency. Finally, it has been concluded that the electron transfer is the main cause of the breast cancer treatment which is the most aggressive type of cancers and is one of the hardest to treat.
Cancer is a principle cause of death in both more and less in economically developed countries due to tobacco use, obesity, physical inactivity, and infections, [
Breast cancer is the second most common cancer over worldwide after lung cancer, the fifth most common cause of cancer death in women. Triple-negative breast cancer tumors relapse more frequently in spite of good initial response to chemotherapy, and have a worse prognosis than hormone receptor-positive, luminal subtypes. New systemic therapies are urgently needed because hormonal therapies and HER2-targeted agents are ineffective in this group of tumors. Poly (ADP-ribose) polymerase inhibitors, angiogenesis inhibitors, EGFR-targeted agents, and src kinase and mTOR inhibitors are among the therapeutic agents being actively investigated in clinical trials in these patients [
Computational studies on the isolated molecules in the gas phase were performed by the aid of GAUSSIAN 03 package. Minimum energy structure was achieved using semi- empirical AM1 method. DFT/6-31**G calculations were performed on the minimum energy structures using the closed shell Hartree-Fock, Becke’s three parameters density functional theory, DFT, [
With respect to DFT calculations, it can be carried out using the basis set B3LYP/ 6-31**G and the energy of the DFT theory can be represented as a function of the electron density as follows:
where
where Ci is the eigenvectors for each molecular orbital eigenfunction ψi and
where
The electron transfer energy (ECT) in the CT-complex between the donor and the acceptor (cation and anion) was calculated according to the following equation [
where ID is the ionization potential of the donor and EA is the electron affinity of the acceptor. C+ is the columbic potential energy of the donor as a cation, and C− is the columbic potential energy of the acceptor as an anion. The columbic potential energy can be calculated, according to the following equation [
where Zi and Zj are the charge densities of two different atoms in a molecule and rij is the distance between two atoms in a molecule of N atoms in angstrom. The electron transfer-band position in nm can be obtained by dividing 1240.824 by the electron transfer energy in electron volts i.e. (Eλ = 1240.824 eV nm).
Ibuprofen (IBF), 2(4-isobutylphenyl) propanoic acid, acts as a non-steroidal anti-in- flammatory drug (NSAID) which always used for relieving pain, antipyretic and anti-inflammatory. About 60% of patients improved by any given NSAID and it is advised that if one does not work that another can be used. Ibuprofen may be considered as weak anti-inflammatory than other NSAIDs. Ibuprofen has a particularly interesting property, and it can exist as a pair of optical isomers that are mirror images of each other. IBF molecules have two conformers R and S as shown in
To give more information about cancer, it is mutual electron transfer between the nucleic acid bases and electron acceptor, i.e. free radicals, drugs even some food like grills and fries. Losing an electron from the nucleic acid bases inside the nucleus produces carcinogenic cell in which the nucleus acts as electron donor to any electron acceptor such as in case of Paracetamol metabolite in the liver, NABQI,
From
Compound | TE au | Ip eV | Ea eV |
---|---|---|---|
S-IBF | −656.5408 | 6.6837 | 0.8879 |
R-IBF | −656.5419 | 6.6766 | 0.9048 |
N.B. Ip is the ionization potential energy and Ea is the electron affinity.
Compound | TE au | Ip eV | Ea eV |
---|---|---|---|
Adenine | −467.17488 | 6.4061 | +1.2672 |
Guanine | −542.37704 | 6.1879 | +1.2828 |
Guanine cation | −542.06199 | 11.91478 | +6.5582 |
Cytosine | −394.82291 | 6.5819 | +1.4768 |
Uracil | −414.70313 | 7.3316 | +1.8626 |
S-ibuprofen in the stomach | −656.5408 | 6.6837 | +0.8879 |
S-ibuprofen in the small intestine | −655.9788 | 0.9015 | −1.4392 |
cationic guanine, in the cancerous cell, which has high electron affinity being equal to 6.5582 eV. In our calculations the guanine cation represents the cancerous cell in this work. Guanine cation in the cancerous cells has high ionization potential energy in water, 7.8293 eV and relatively high electron affinity in water, 2.5486 eV,
From the DFT calculations, the high electron affinity of guanine cation in the carcinogenic cell is equal to 6.5582 eV and the heat content change from guanine to guanine cation equals 197.276 k cal mol−1. The condition of treatment of cancer by drug anions can be illustrated as follows:
where Eet is the electron transfer energy, Ip is the ionization potential energy of the IBF-anions as a donor, C− is the columbic potential energy of anions , Ea is the electron affinity of the guanine cation as an acceptor and C+ is the columbic potential energy of guanine cation in the gas phase using DFT-6-31**G calculations.
Ip(IBF anion) (0.9015 eV) and Ea(guanine cation) is the electron affinity of guanine cation being equal to 6.5582 eV,
Matthew Gdovin and others have found out an experimental method to kill the cancer cells in two hour by injection of ethanolic solution of nitrobenzaldehyde and stay sometimes to let the solution diffuses in the breast tumor and then aim uv-light on the tumor for about two hours causing the cancerous cells become very acidic inside then the breast tumor disappears because the carcinogenic cells commit suicide in the strong acidic medium as explained by Gdovin group [
After the incidence of the uv-light on the ethanolic solution of nitrobenzaldehyde, the molecules promote from the ground state to the excited states. From the previous Tables 3-5 it can be concluded that nitrobenzaldehydes have low ionization potential energies in their excited states and regarding the high electron affinity of cationic guanine, in ethanolic solution equals to 2.676513 eV,
From
Excited state singlet-A | Eigenvectors | Transition | ΔE eV | λcalc. nm | F | Ex Ip eV |
---|---|---|---|---|---|---|
Excited State 1 | ||||||
39− > 40 39− > 41 | 0.63499 −0.26192 | ψm− > ψm+1 ψm− > ψm+2 | 3.3025 | 375.43 | 0.0000 | 1.533128 |
Excited State 2 | ||||||
37− > 42 38− > 40 | 0.14475 0.67061 | ψm−2− > ψm+3 | 3.8179 | 324.74 | 0.0357 | 1.576936 |
Excited State 3 | ||||||
36− > 40 36− > 41 | 0.65583 0.20150 | ψm−3− > ψm+1 ψm−3− > ψm+2 | 3.8198 | 324.58 | 0.0000 | 1.569131 |
Excited state singlet-A | Eigenvectors | Transition | ΔE eV | λcalc. nm | f | Ex Ip eV |
---|---|---|---|---|---|---|
Excited state 1 | ||||||
39− > 40 39− > 41 | −0.38190 0.56353 | ψm− > ψm+1 ψm− > ψm+2 | 3.6203 | 342.47 | 0.0001 | 1.264399 |
Excited state 2 | ||||||
36− > 40 36− > 41 39− > 40 39− > 41 | 0.63656 0.13159 0.15913 0.13339 | ψm−3− > ψm+1 ψm−3− > ψm+2 ψm− > ψm+1 ψm− > ψm+2 | 3.9108 | 342.47 | 0.0001 | 1.464898 |
Excited state 3 | ||||||
36− > 40 39− > 40 39− > 41 | −0.19827 0.56276 0.35182 | ψm−3− > ψm+1 ψm− > ψm+1 ψm− > ψm+2 | 4.0769 | 304.11 | 0.0000 | 1.44943 |
Excited state singlet-A | Eigenvectors | Transition | ΔE eV | λcalc. nm | f | Ex Ip eV |
---|---|---|---|---|---|---|
Excited state 1 | ||||||
39− > 40 39− > 41 | 0.65966 −0.16240 | ψm− > ψm+1 ψm− > ψm+2 | 3.0039 | 412.75 | 0.0000 | 1.5717400 |
Excited state 2 | ||||||
36− > 40 36− > 41 39− > 41 | 0.57540 0.10679 −0.34330 | ψm−3− > ψm+1 ψm−3− > ψm+2 ψm− > ψm+2 | 3.7879 | 327.32 | 0.0000 | 1.4422677 |
Excited state 3 | ||||||
37− > 41 38− > 40 | −0.15258 0.66388 | ψm−2− > ψm+1 ψm−1− > ψm | 3.7946 | 326.74 | 0.0757 | 1.5841700 |
Solvent | TE au | Ip eV | Ea eV |
---|---|---|---|
Ethanol | −542.189198 | 7.959607 | 2.676513 |
Diethyl ether | −542.166122 | 8.750642 | 3.447684 |
Water | −542.193720 | 7.829264 | 2.548620 |
Gas | −542.079515 | 11.91478 | 6.558219 |
negative sign of the electron transfer energy, −3.620429 eV, which means the spontaneity of the electron transfer from the second excited state of p-nitrobenzaldehyde to guanine cation in ethanolic solution as calculated below:
Therefore the negative sign of the electron transfer energy, Eet, indicates to the spontaneity of the electron transfer from ethanolic solution of p-nitrobenzaldehyde to guanine cation to compensate the electron deficiency in guanine cation in the cancerous cells in presence of uv-light (325 nm).
From the previous
From
Therefore, ethanolic solution of o-nitrobenzaldehyde compensates the electron deficiency of guanine cation in presence of uv-irradiation at λ = 327 nm.
It is important to indicate to diethyl ether as solvent instead of ethanol in ethanolic solution of nitrobenzaldehyde and it is better because the electron affinity of guanine cation in diethyl ether is higher than in case of ethyl alcohol,
Ethanol is the solvent in the injected solution of nitrobenzaldehyde in the breast tumor and it is metabolized to acetaldehyde by alcohol dehydrogenase (ADH) enzyme. The aldehyde dehydrogenase enzyme (ALDH) is responsible for oxidation of acetaldehyde to acetic acid. The degradation of acetaldehyde depends on the activity of this enzyme. The total Alcohol dehydrogenase activity is significantly higher in cancer tissues than in these healthy organs (e.g. liver, stomach, esophagus, colorectum). The activity of ADH is much higher than the activity of ALDH. The cancer cells have a greater capability for ethanol oxidation but less ability to remove hydrogen from acetaldehyde than in normal tissues. In addition, significant differences of ADH isoenzymes activities between cancer tissues and healthy organs may be a factor intensifying carcinogenesis by the increased ability to acetaldehyde formation from ethanol and disorders in metabolism of some biologically important substances (e.g. retinoic acid). The changes in activity of particular ADH isoenzymes in the sera of patients with different cancers, seemed to be caused by release of these isoenzymes from cancer cells, and may be useful for diagnostics of this cancer. The particular isoenzymes of ADH present in the serum may indicate to the cancer localization [
It is important to know the effect of the uv-light on ethanol itself as solvent. Of course the ethanol molecules promote to the excited states in presence of the uv-light depending on the wavelength as shown below:
From
It can be noticed from the previous values of ethanol charge densities that the hydrogen atom attached with the hydroxyl oxygen atom has the highest positive charge, 0.513135,
Excited state singlet-A | Eigenvectors | Transition | ΔE eV | λcalc. nm | f | Ex Ip eV |
---|---|---|---|---|---|---|
Excited state 1 | ||||||
13− > 14 13− > 15 | 0.67973 −0.17057 | ψm− > ψm+1 ψm− > ψm+2 | 6.3756 | 194.47 | 0.0002 | 0.108383 |
Excited state 2 | ||||||
13− > 14 13− > 15 13− > 16 | 0.18000 0.65734 0.14683 | ψm− > ψm+1 ψm− > ψm+2 ψm− > ψm+3 | 7.0224 | 176.56 | 0.0005 | 0.201893 |
Excited state 3 | ||||||
13− > 14 13− > 15 | −0.16170 0.68251 | ψm− > ψm+1 ψm−− > ψm+2 | 7.3207 | 169.36 | 0.0495 | 0.178419 |
in cancerous cells which performs much effort to do, as reported by Wojciech [
So, the cure of breast cancer tumor by Matthew Gdovin [
No. | Atom | Charge density |
---|---|---|
1 | C | −0.666689 |
2 | C | −0.239419 |
3 | O | −0.660615 |
4 | H | 0.193943 |
5 | H | 0.220397 |
6 | H | 0.220457 |
7 | H | 0.209422 |
8 | H | 0.209369 |
9 OH | H | 0.513135 |
1) It is good for the health to take ibuprofen drug regularly to avoid cancers of gastrointestine, protostate, breast and lung and from general point of view, it is better to use the carboxylic acid drugs for the cancer treatment.
2) The electron transfer from ethanolic solution of nitrobenzaldehydes to cancerous cells in presence of uv-irradiation is the real cause in the treatment of breast cancer in two hours by Matthew Gdovin group rendering the cancerous cells to be normal rendering the cancerous cells to be normal and there is not suicide of the cancerous cells.
El-Shahawy, A. (2017) DFT-Comparison of Anti-Cancer Effect of Ibuprofen Drug Anions and Breast Cancer Treatment by Ethanolic Solution of Nitrobenzaldehyde in Two Hours. Computational Chemistry, 5, 9-21. http://dx.doi.org/10.4236/cc.2017.51002