MyMedR

Fulltext Butylated hydroxytoluene analogs: synthesis and evaluation of their multipotent antioxidant activities

Yehye WA, Abdul Rahman N, Alhadi AA, Khaledi H, Weng NS, Ariffin A

Molecules, 2012 Jun 25;17(7):7645-65.

PMID: 22732881 DOI: 10.3390/molecules17077645

A computer-aided predictions of antioxidant activities were performed with the Prediction Activity Spectra of Substances (PASS) program. Antioxidant activity of compounds 1, 3, 4 and 5 were studied using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and lipid peroxidation assays to verify the predictions obtained by the PASS program. Compounds 3 and 5 showed more inhibition of DPPH stable free radical at 10⁻⁴ M than the well-known standard antioxidant, butylated hydroxytoluene (BHT). Compound 5 exhibited promising in vitro inhibition of Fe²⁺-induced lipid peroxidation of the essential egg yolk as a lipid-rich medium (83.99%, IC₅₀ 16.07 ± 3.51 μM/mL) compared to α-tocopherol (α-TOH, 84.6%, IC₅₀ 5.6 ± 1.09 μM/mL). The parameters for drug-likeness of these BHT analogues were also evaluated according to the Lipinski’s “rule-of-five” (RO5). All the BHT analogues were found to violate one of the Lipinski’s parameters (LogP > 5), even though they have been found to be soluble in protic solvents. The predictive polar surface area (PSA) and absorption percent (% ABS) data allow us to conclude that they could have a good capacity for penetrating cell membranes. Therefore, one can propose these new multipotent antioxidants (MPAOs) as potential antioxidants for tackling oxidative stress and lipid peroxidation processes.

Fulltext 2-[4-Acetyl-5-(biphenyl-4-yl)-4,5-dihydro-1,3,4-oxadiazol-2-yl]phenyl acetate

Yehye WA, Ariffin A, Rahman NA, Ng SW

Acta Crystallogr Sect E Struct Rep Online, 2010 Mar 20;66(Pt 4):o878.

PMID: 21580697 DOI: 10.1107/S1600536810009621

In the title mol-ecule, C(24)H(20)N(2)O(4), the five-membered oxadiazole ring is nearly planar (r.m.s. deviation = 0.053 Å) and the phenyl ring of the biphenyl unit attached to it forms a dihedral angle of 73.2 (1)°; the other phenyl ring is close to coplanar with the oxadiazole ring [dihedral angle = 6.2 (2)°].

Fulltext N'-[(Biphenyl-4-yl)methyl-ene]-2-[(3,5-di-tert-butyl-4-hydroxy-benz-yl)sulfan-yl]acetohydrazide

Yehye WA, Ariffin A, Rahman NA, Ng SW

Acta Crystallogr Sect E Struct Rep Online, 2010;66(Pt 4):o734.

PMID: 21580580 DOI: 10.1107/S1600536810006884

In the title compound, C(30)H(36)N(2)O(2)S, the dihedral angle between the two aromatic rings of the biphenyl residue is 31.2 (1)°. The two methyl-ene C atoms subtend an angle of 99.9 (1)° at the S atom. In the crystal, mol-ecules form inversion dimers linked by pairs of N-H⋯O hydrogen bonds. The hydroxyl group is shielded by the tert-butyl residues and is therefore not involved in any hydrogen bonding.

Fulltext Dipyridinium 2,2'-dithio-dinicotinate

Yehye WA, Ariffin A, Rahman NA, Ng SW

Acta Crystallogr Sect E Struct Rep Online, 2009;65(Pt 5):o1068.

PMID: 21583884 DOI: 10.1107/S1600536809013543

The dianion of the title salt, 2C(5)H(6)N(+)·C(12)H(6)N(2)O(4)S(2) (2-), lies on a special position of 2 site symmetry that relates one thio-nicotinate part to the other, and the dihedral angle between the niotinate planes is 89.2 (2)°. The pyridinium cations are hydrogen bonded to the carboxyl-ate group by way of N-H⋯O links.

Fulltext 2-[(3,5-Di-tert-butyl-4-hydroxy-benz-yl)-sulfan-yl]-N'-isopropyl-ideneaceto-hydrazide

Yehye WA, Ariffin A, Ng SW

Acta Crystallogr Sect E Struct Rep Online, 2009;65(Pt 4):o730.

PMID: 21582464 DOI: 10.1107/S1600536809007843

The title compound, C(20)H(32)N(2)O(2)S, the condensation product of a thio-acetohydrazine and acetone, has a two-coordinate S atom and the angle at this atom is 100.7 (1)°. The (CH(3))C=N-NH-C(O)- substituent engages in N-H⋯O hydrogen-bonding inter-actions with the substituent of an adjacent mol-ecule across a center of inversion, generating a dimeric structure.

Fulltext 2-(3,5-Di-tert-butyl-4-hydroxy-benzyl-sulfan-yl)-N'-(3-methoxy-benzyl-idene)acetohydrazide

Yehye WA, Ariffin A, Rahman NA, Ng SW

Acta Crystallogr Sect E Struct Rep Online, 2009;65(Pt 9):o2112.

PMID: 21577527 DOI: 10.1107/S1600536809030645

The title compound, C(25)H(34)N(2)O(3)S, is a derivative of N'-benzyl-ideneacetohydrazide having substituents on the acetyl and benzylidenyl parts, and displays a planar C(carbon-yl)-NH-NC(anis-yl) fragment [torsion angle = 174.9 (3)°]. The -NH- unit forms an N-H⋯O hydrogen bond with the carbonyl O atom of an inversion-related mol-ecule.

Fulltext Biphenyl-4-carbaldehyde azine

Yehye WA, Ariffin A, Rahman NA, Ng SW

Acta Crystallogr Sect E Struct Rep Online, 2008;64(Pt 12):o2444.

PMID: 21581412 DOI: 10.1107/S1600536808038622

The complete mol-ecule of the title compound, C(26)H(20)N(2), is generated by crystallographic inversion symmetry. The terminal phenyl ring is twisted by 19.2 (1)° with respect to the adjacent phenyl-ene ring.

Fulltext N'-(3-Bromo-5-chloro-2-hydroxy-benzyl-idine)-2-hydroxy-benzohydrazide

Yehye WA, Ariffin A, Rahman NA, Ng SW

Acta Crystallogr Sect E Struct Rep Online, 2008;64(Pt 12):o2438.

PMID: 21581406 DOI: 10.1107/S1600536808038634

In the approximately planar title mol-ecule, C(14)H(10)BrClN(3)O(2), the dihedral angle between the aromatic ring planes is 5.79 (12)°. The conformation is stabilized by intra-molecular O-H⋯N and N-H⋯O hydrogen bonds and an inter-molecular O-H⋯O link leads to chains in the crystal propagating in [001].

Fulltext N'-(3,5-Di-tert-butyl-4-hydroxy-benzyl-idene)-2-hydroxy-benzohydrazide methanol solvate

Yehye WA, Ariffin A, Ng SW

Acta Crystallogr Sect E Struct Rep Online, 2008;64(Pt 8):o1452.

PMID: 21203167 DOI: 10.1107/S1600536808020746

The asymmetric unit of the title compound, C(22)H(28)N(2)O(3)·CH(4)O, consists of two independent Schiff base mol-ecules and two independent methanol solvent mol-ecules. In one Schiff base mol-ecule, the 2-hydr-oxy group forms an intra-molecular hydrogen bond with the amide O atom, whereas in the other Schiff base mol-ecule, the 2-hydr-oxy-substituted benzene ring is oriented so that the 2-hydr-oxy group serves as hydrogen-bond acceptor for the amide NH group. In the crystal structure, Schiff base mol-ecules inter-act with methanol solvent to furnish a hydrogen-bonded chain.

Fulltext (2,4-Dimethoxy-benzyl-idene)-2-hydroxy-benzohydrazide ethanol solvate

Yehye WA, Ariffin A, Ng SW

Acta Crystallogr Sect E Struct Rep Online, 2008 May 03;64(Pt 6):o961.

PMID: 21202691 DOI: 10.1107/S1600536808011768

In the planar title mol-ecule, C(16)H(16)N(2)O(4)·C(2)H(6)O, the planar Schiff base molecule is linked to the ethanol solvent mol-ecule by a hydr-oxy-amide hydrogen bond. The hydr-oxy group of the ethanol mol-ecule is a hydrogen-bond donor to the double-bonded N atom of an adjacent Sciff base, pairs of interactions taking place across a center of symmetry and giving rise to a hydrogen-bonded dimer.

Fulltext 2-Hydr-oxy-(2-methyl-1H-indol-3-ylmethyl-idene)benzohydrazide ethanol solvate

Yehye WA, Ariffin A, Ng SW

Acta Crystallogr Sect E Struct Rep Online, 2008;64(Pt 6):o960.

PMID: 21202690 DOI: 10.1107/S1600536808011756

In the title compound, C(17)H(15)N(3)O(2)·C(2)H(6)O, Schiff base molecules are linked by a hydr-oxy-amido hydrogen bond into a helical chain running along the b axis. This chain is consolidated by two other hydrogen bonds; the ethanol solvent mol-ecule is a hydrogen-bond donor to the amide group and a hydrogen-bond acceptor for the indolyl NH group of an adjacent Schiff base mol-ecule.

Understanding the chemistry behind the antioxidant activities of butylated hydroxytoluene (BHT): a review

Yehye WA, Rahman NA, Ariffin A, Abd Hamid SB, Alhadi AA, Kadir FA, et al.

Eur J Med Chem, 2015 Aug 28;101:295-312.

PMID: 26150290 DOI: 10.1016/j.ejmech.2015.06.026

Hindered phenols find a wide variety of applications across many different industry sectors. Butylated hydroxytoluene (BHT) is a most commonly used antioxidant recognized as safe for use in foods containing fats, pharmaceuticals, petroleum products, rubber and oil industries. In the past two decades, there has been growing interest in finding novel antioxidants to meet the requirements of these industries. To accelerate the antioxidant discovery process, researchers have designed and synthesized a series of BHT derivatives targeting to improve its antioxidant properties to be having a wide range of antioxidant activities markedly enhanced radical scavenging ability and other physical properties. Accordingly, some structure-activity relationships and rational design strategies for antioxidants based on BHT structure have been suggested and applied in practice. We have identified 14 very sensitive parameters, which may play a major role on the antioxidant performance of BHT. In this review, we attempt to summarize the current knowledge on this topic, which is of significance in selecting and designing novel antioxidants using a well-known antioxidant BHT as a building-block molecule. Our strategy involved investigation on understanding the chemistry behind the antioxidant activities of BHT, whether through hydrogen or electron transfer mechanism to enable promising anti-oxidant candidates to be synthesized.

Fulltext Rational Design and Synthesis of New, High Efficiency, Multipotent Schiff Base-1,2,4-triazole Antioxidants Bearing Butylated Hydroxytoluene Moieties

Yehye WA, Abdul Rahman N, Saad O, Ariffin A, Abd Hamid SB, Alhadi AA, et al.

Molecules, 2016 Jun 28;21(7).

PMID: 27367658 DOI: 10.3390/molecules21070847

A new series of multipotent antioxidants (MPAOs), namely Schiff base-1,2,4-triazoles attached to the oxygen-derived free radical scavenging moiety butylated hydroxytoluene (BHT) were designed and subsequently synthesized. The structure-activity relationship (SAR) of the designed antioxidants was established alongside the prediction of activity spectra for substances (PASS). The antioxidant activities of the synthesized compounds 4-10 were tested by the DPPH bioassay. The synthesized compounds 4-10 inhibited stable DPPH free radicals at a level that is 10(-4) M more than the well-known standard antioxidant BHT. Compounds 8-10 with para-substituents were less active than compounds 4 and 5 with trimethoxy substituents compared to those with a second BHT moiety (compounds 6 and 7). With an IC50 of 46.13 ± 0.31 µM, compound 6 exhibited the most promising in vitro inhibition at 89%. Therefore, novel MPAOs containing active triazole rings, thioethers, Schiff bases, and BHT moieties are suggested as potential antioxidants for inhibiting oxidative stress processes and scavenging free radicals, hence, this combination of functions is anticipated to play a vital role in repairing cellular damage, preventing various human diseases and in medical therapeutic applications.

Fulltext N-Acetyl-2-hydroxy-N'-[methoxy(1-methylindol-2-yl)methyl]benzohydrazide

Yehye WA, Rahman NA, Ariffin A, Ng SW

Acta Crystallogr Sect E Struct Rep Online, 2008 Aug 23;64(Pt 9):o1824.

PMID: 21201799 DOI: 10.1107/S1600536808026846

In the crystal structure of the title Schiff-base, C(20)H(21)N(3)O(4), the amino group forms an N-H⋯O hydrogen bond to the acetyl group of an adjacent mol-ecule, forming a zigzag chain. The 2-hydr-oxy group is inter-nally hydrogen bonded to the amido group though an O-H⋯O hydrogen bond.

Effect of Bulky Functional Groups on Donor and Acceptor Interactions and their Photoluminescence Properties

Woon KL, Mustapa SAS, Mohd Jamel NS, Lee VS, Zakaria MZ, Ariffin A

Chemphyschem, 2020 Sep 17.

PMID: 32940952 DOI: 10.1002/cphc.202000612

Material designs that use donor and acceptor units are often found in organic optoelectronic devices. Molecular level insight into the interactions between donors and acceptors are crucial for understanding how such interactions can modify the optical properties of the organic optoelectronic materials. In this paper, tris(4-(tert-butyl)phenyl)amine (pTPA) was synthesized as a donor in order to compare with unmodified triphenylamine (TPA) in a donor-acceptor system by having 2,4,6-triphenyl-1,3,5-triazine (TRZ) as an acceptor. Dimerization of donors and acceptors occurred in solvent when the concentration of solute is high. At 0 K, using a polarizable continuum model, the nitrogen atom of TPA is found to stack on top of the center of triazine of TRZ, whereas such alignment is offset in pTPA and TRZ. We attributed such alignment in TPA-TRZ as the result of attractive interactions between partial localization of 2pz electrons at the nitrogen atom of TPA and the π deficiency of triazine in TPA-TRZ. By taking into account random motions of the solvent effect at 300 K in quantum molecular dynamics and classical molecular dynamics simulations to interpret the marked difference in emission spectra between TPA-TRZ and pTPA-TRZ, it was revealed that the attractive interaction between pTPA and TRZ in toluene is weaker than TPA and TRZ. Because of the weaker attractive interaction between pTPA and TRZ in toluene, the dimers adopted numerous ground state conformations resulting in broad emission bands superimposed with multiple small Gaussian peaks. This is in contrast to TPA-TRZ which has only one dominant dimer conformation. This study demonstrates that the strength of intermolecular interactions between donors and acceptors should be taken into consideration in designing supramolecular structures.

Relating molecular descriptors to frontier orbital energy levels, singlet and triplet excited states of fused tricyclics using machine learning

Woon KL, Chong ZX, Ariffin A, Chan CS

J Mol Graph Model, 2021 06;105:107891.

PMID: 33765526 DOI: 10.1016/j.jmgm.2021.107891

Fused tricyclic organic compounds are an important class of organic electronic materials. In designing molecules for organic electronics, knowing what chemical structure that be used to tune the molecular property is one of the keys that can help to improve the material performance. In this research, we applied machine learning and data analytic approaches in addressing this problem. The energy states (Lowest Unoccupied Molecular Orbital (HOMO), Highest Occupied Molecular Orbitals (LUMO), singlet (Es) and triplet (ET) energy) of more than 10 thousand fused tricyclics are calculated. Corresponding descriptors are also generated. We find that the Coulomb matrix is a poorer descriptor than high-level descriptors in a multilayer perceptron neural network. Correlations as high as 0.95 is obtained using a multilayer perceptron neural network with Mean Absolute Error as low as 0.08 eV. The descriptors that are important in tuning the energy levels are revealed using the Random Forest algorithm. Correlations of such descriptors are also plotted. We found that the higher the number of tertiary amines, the deeper are the HOMO and LUMO levels. The presence of NN in the aromatic rings can be used to tune the ES. However, there is no single dominant descriptor that can be correlated with the ET. A collection of descriptors is found to give a far better correlation with ET. This research demonstrated that machine learning and data analytics in guiding how certain chemical substructures correlate with the molecule energy states.

Development and validation of a new simplified anatomic trauma mortality score

Tan JH, Mohamad Y, Imran Alwi R, Henry Tan CL, Chairil Ariffin A, Jarmin R

Injury, 2019 May;50(5):1125-1132.

PMID: 30686543 DOI: 10.1016/j.injury.2019.01.027

BACKGROUND: Most trauma mortality prediction scores are complex in nature. GAP (Glasgow Coma Scale, Age, Systolic blood pressure) and mGAP (mechanism, Glasgow Coma Scale, Age, Systolic blood pressure) scores are relatively simple scoring tools. However, these scores were not validated in low and middle income countries including Malaysia and its accuracies are influenced by the fluctuating physiologic parameters. This study aims to develop a relevant simplified anatomic trauma scoring system for the local trauma patients in Malaysia.

METHOD: A total of 3825 trauma patients from 2011 to 2016 were extracted from the Hospital Sultanah Aminah Trauma Surgery Registry. Patients were split into a development sample (n = 2683) and a validation sample (n = 1142). Univariate analysis is applied to identify significant anatomic predictors. These predictors were further analyzed using multivariable logistic regression to develop the new score and compared to existing score systems. The quality of prediction was determined regarding discrimination using sensitivity, specificity and receiver operating characteristic [ROC] curve.

RESULTS: Existing simplified score systems (GAP & mGAP) revealed areas under the ROC curve of 0.825 and 0.806. The newly developed HeCLLiP (Head, cervical spine, lung, liver, pelvic fracture) score combines only five anatomic components: injury involving head, cervical spine, lung, liver and pelvic bone. The probabilities of mortality can be estimated by charting the total score points onto a graph chart or using the cut-off value of (>2) with a sensitivity of 79.2 and specificity of 70.6% on the validation dataset. The HeCLLiP score achieved comparable values of 0.802 for the area under the ROC curve in validation samples.

CONCLUSION: HeCLLiP Score is a simplified anatomic score suited to the local Malaysian population with a good predictive ability for trauma mortality.

Fulltext Endovascular Aneurysm Repair (EVAR) for infra-renal Abdominal Aortic Aneurysm(AAA) under Local Anaesthesia - Initial Experience in Hospital Kuala Lumpur

Syed Alwi SA, Zainal Ariffin A, Hanif H, Naresh G

Med J Malaysia, 2012 Oct;67(5):503-5.

PMID: 23770868

This is our initial report on the first 4 cases of infra-renal abdominal aortic aneurysms undergoing Endovascular Aneurysm Repair (EVAR) with local anaesthesia, controlled sedation and monitoring by an anaesthetist. All 4 patients were males with a mean age of 66.7 years. Only one (1) required ICU stay of 2 days for cardiac monitoring due to bradycardia and transient hypotension post procedure. No mortality or major post operative morbidity was recorded and the mean hospital stay post procedure was 3.5 days (range 2-5 days).

Derivatives of Pyridazine with Phenoxazine and 9,9-Dimethyl-9,10-dihydroacridine Donor Moieties Exhibiting Thermally Activated Delayed Fluorescence

Skhirtladze L, Bezvikonnyi O, Keruckienė R, Dvylys L, Mahmoudi M, Labanauskas L, et al.

Materials (Basel), 2023 Feb 02;16(3).

PMID: 36770299 DOI: 10.3390/ma16031294

Two compounds based on pyridazine as the acceptor core and 9,9-dimethyl-9,10-dihydroacridine or phenoxazine donor moieties were designed and synthesized by Buchwald-Hartwig cross-coupling reaction. The electronic, photophysical, and electrochemical properties of the compounds were studied by ultraviolet-visible spectroscopy (UV-vis), photoluminescence spectrometry, differential scanning calorimetry, thermogravimetric analysis, and cyclic voltammetry. The compounds are characterized by high thermal stabilities. Their 5% weight loss temperatures are 314 and 336 °C. Complete weight loss of both pyridazine-based compounds was detected by TGA, indicating sublimation. The derivative of pyridazine and 9,9-dimethyl-9,10-dihydroacridine is capable of glass formation. Its glass transition temperature is 80 °C. The geometries and electronic characteristics of the compounds were substantiated using density functional theory (DFT). The compounds exhibited emission from the intramolecular charge transfer state manifested by positive solvatochromism. The emission in the range of 534-609 nm of the toluene solutions of the compounds is thermally activated delayed fluorescence with lifetimes of 93 and 143 ns, respectively.

Switching thermally activated delayed fluorescence to room temperature phosphorescence for oxygen sensing: Effect of donor substituents of trifluoromethylphenyl

Skhirtladze L, Keruckiene R, Bezvikonnyi O, Mahmoudi M, Volyniuk D, Leitonas K, et al.

Spectrochim Acta A Mol Biomol Spectrosc, 2024 Feb 05;306:123531.

PMID: 37890326 DOI: 10.1016/j.saa.2023.123531

Two compounds consisting of electron-accepting trifluoromethylphenyl moiety and electron-donating phenoxazine and phenothiazine moieties were designed and synthesized via Buchwald-Hartwig coupling reaction. Thermal, photophysical, and electrochemical properties of the compounds are discussed. Only compound with phenothiazine form molecular glass, with glass transition temperatures of 90 °C. The geometry and electronic characteristics of the compounds were substantiated within density functional theory (DFT). 10,10'-(2-(Trifluoromethyl)-1,4-phenylene)bis(10H-phenoxazine) shows efficient thermally activated delayed fluorescence with high spin-orbit coupling values. 10,10'-(2-(Trifluoromethyl)-1,4-phenylene)bis(10H-phenothiazine) as efficient room-temperature phosphor shows high oxygen sensitivity.

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