Molecular Crystals and Liquid Crystals

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Some physico-chemical characteristics of

amino-acid derivatives containing rest of
1,2,4-triazole-3,4-di-substituted with potential
antitumoral activity

Corina Cheptea, Valeriu Sunel, Shardi Manahedji Ardeshir, Ana Cezarina

Morosanu & Dana Ortansa Dorohoi

To cite this article: Corina Cheptea, Valeriu Sunel, Shardi Manahedji Ardeshir, Ana Cezarina
Morosanu & Dana Ortansa Dorohoi (2020) Some physico-chemical characteristics of amino-acid
derivatives containing rest of 1,2,4-triazole-3,4-di-substituted with potential antitumoral activity,
Molecular Crystals and Liquid Crystals, 697:1, 97-107, DOI: 10.1080/15421406.2020.1731081

To link to this article: https://doi.org/10.1080/15421406.2020.1731081

Published online: 12 Jul 2020.

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MOLECULAR CRYSTALS AND LIQUID CRYSTALS
2020, VOL. 697, NO. 1, 97–107
https://doi.org/10.1080/15421406.2020.1731081

Some physico-chemical characteristics of amino-acid

derivatives containing rest of 1,2,4-triazole-3,4-di-
substituted with potential antitumoral activity
Corina Chepteaa, Valeriu Sunelb, Shardi Manahedji Ardeshirb,
Ana Cezarina Morosanuc, and Dana Ortansa Dorohoic
a
Department of Biomedical Sciences, Grigore T. Popa University of Medicine and Pharmacy of Iasi,
Faculty of Medical Bioengineering, Iasi, Romania; bFaculty of Chemistry, Al. I. Cuza University of Iasi,
Iasi, Romania; cFaculty of Physics, Al. I. Cuza University of Iasi, Iasi, Romania

ABSTRACT KEYWORDS
Dipeptide derivatives from p-aminobenzoyl-phenylglycine and p-ami- antimetabolites; dipeptides;
nobenzoyl-phenylalanine were grafted on 1,2,4-triazole heterocycle in 1,2,4-triazole heterocycle;
order to get new substances with potential biological activity. The NMR and FTIR
Spectroscopy;
compounds synthetized and characterized in this paper have a struc- p-aminobenzoyl-phenylalan-
ture that fits in the antimetabolites category, products used to treat ine; p-aminobenzoyl-
malignant tumors. The presence of several bioactive groups in the phenylglycine; Spartan
same molecule permits us to study the chemical structure - biological 14 software
activity correlation based on computational analyses using SPARTAN’14
software. Some correlations between the molecular parameters estab-
lished with Spartan’14 software are evidenced in this paper.

1. Introduction
The current trend in chemotherapy of malignant tumors is characterized by predomin-
antly use of the antimetabolites. A series of researchers have synthesized a number of
a-amino acid derivatives, some of them having a cytostatic activity, exerted by the
antagonist effect of the aminic acid or dipeptide, respectively [1–8]. In the structure of
the new substances they have synthesized are present, among other atomic groups, the
1,2,4-triazole heterocycle, the indazole ring and the peptide fragment. The triazole deriv-
atives are important through their antifungal [9–11], antimicrobial [12,13], anti-inflam-
matory [14,15], hypnotic and sedative [16], analgesic [17,18], cardioprotective [19],
antitumoral [13] actions. Indazole and its derivatives are found in the composition of
many drugs with extremely different pharmacological properties: antihistamine [20],
antiviral [21], antimicrobial [22,23], cytostatic [24–26], anti-inflammatory [27], anal-
gesic-antipyretic [28], anti-HIV [29], antiarrhythmic [30], antifungal [31], or gluco-
corticoid receptor antagonists [32]. Peptide fragment has a well-defined role in the
human body and has interesting biological properties [2,7,33–36]. Phenyl glycine as well
as phenylalanine and their acylated derivatives with the substituted benzoyl fragment in
para-position, taking part in the metabolism of living organisms, reduces the toxicity of
some medicinal products, also facilitating their access to the cellular level [2,8,14,37–43].

CONTACT Ortansa Dorohoi ddorohoi@uaic.ro Faculty of Phisics, Al. I. Cuza University of Iasi, Iasi, Romania
ß 2020 Taylor & Francis Group, LLC
98 C. CHEPTEA ET AL.

The phenylglycine and phenylalanine derivatives contain in their structure a p-amino-

benzoic acid fragment, which is important, especially for the fact that this p-aminoben-
zoic acid enters the composition of the folic acid, and it is indispensable product for the
metabolism of deoxyribonucleic acids [44].
In order to obtain derivatives with reduced toxicity and high therapeutic action, a
series of syntheses were performed by replacing the hydrogen of the amino group in
the molecule of the N-(p-aminobenzoyl)-D,L-phenylglycine and N-(p-aminobenzoyl)-L-
phenylalanine with the 5-mercapto-1,2,4-triazole-3,4-disubstituted heterocyclic system.
V. Sunel and collaborators have synthesized and studied a range of substances, D,L-phe-
nylglycine and L-phenylalanine derivatives, which have been shown to be active against
various pathogens [14,41,45,46].
It is interesting to study the mutual influence of the three components present in the
same molecule as well as their contribution to the global biological activity of
the substance.

2. Materials and methods

The reagents used in this paper were purchased from Sigma-Aldrich, Merck, Fluke and
S.C. Chemical Company SA. FT-IR spectra were recorded with FT-IR spectrophotom-
eter (ATR) Br€ ucker Tensor-27; 1H-NMR analysis was performed with Br€ ucker ARX400
spectrometer (5 mm QNP probe; 1H/13C/31P/19F) and elemental analysis with Exeter
Analytical CE 440 elemental analyzer. The melting points of the obtained compounds
were determined with a Mel-Temp melting point module, provided with a digital
thermometer. The composition and structure of the studied in this paper compounds
were determined by chemical (elemental) analysis and spectral analysis (FT-IR, 1H-
NMR). The optimized structures and the molecular parameters of the studied molecules
(IV–IX) were established by using Spartan 14 software [47] with Density Functional
EDF2 model and 6-31 G
basis set. Spartan 14 is a molecular modeling and computa-
tional chemistry application from Wavefunctions Inc. Spartan applies computational
chemistry methods (theoretical models) to many standard tasks that provide calculated
data applicable to the determination of molecular shape conformation, structure (equi-
librium and transition state geometry), NMR, IR, Raman, and UV-visible spectra,
molecular properties, reactivity, and selectivity. The values computed using Spartan offer
valuable information about spatial distribution of atoms in the optimized structures, the
reactivity and ability of the new synthetized molecules to penetrate the membranes in
interaction with human body.

3. Results and discussions

The synthesis of the novel combinations involves different stages, up to reaction of
1,2,4-triazole derivatives with N-(p-aminobenzoyl)-D,L-phenylglycine and N-(p-amino-
benzoyl)-L-phenylalanine, respectively, schematically shown in Scheme 1.
The structure of the synthesized triazole derivatives [23] but also of the intermediate
compounds was investigated by elemental and spectral analysis (FT-IR, 1H-NMR). It is
known that the aminolysis reaction of the esters depends on the reactivity both of the
 MOLECULAR CRYSTALS AND LIQUID CRYSTALS 99

Scheme 1. The synthesis route of 3-[(5’-nitro-1H-indazole-1’-yl)-methyl]-4-aryl-1,2,4-triazole-5-(a-thioa-

cetyl) peptides (IV – IX).

amine and of the ester. The amine group involved in the syntheses, presented in the
paper, has a lower basicity, hence a lower reactivity, given its role as a nucleophilic
agent. The low reactivity of the amine group is compensated by the high reactivity of
the thioacetic ester.
The final compounds (IV-IX) studied in this paper 3-[(5’-nitro-1H-indazole-1’-yl)-
methyl]  4-aryl-1,2,4-triazole-5-(a-thioacetyl) peptides were obtained by the following
general procedure: in a suspension of 0.01 ml ester (I-III) in 100 ml anhydrous dioxane
0.02 mole p-aminobenzoyl-phenylglycine, respectively p-aminobenzoyl-phenylalanine,
100 C. CHEPTEA ET AL.

were added and the mixtures was heated at 85–90  C for 5 h. After cooling, from the
reaction mixture in water a precipitate was obtained, which, after purification, by
repeated recrystallizations from acetone and anhydrous ethanol, became white crystals.
The obtained compounds are denominated as it follows:

 3-[(5’-nitro-1H-indazole-1’-yl)-methyl]-4-phenyl-1,2,4-triazole-5-[(a-thioacetyl)
-aminobenzoyl]-D,L-phenylglycine (IV);
 3-[(5’-nitro-1H-indazole-1’-yl)-methyl]-4-(p-tolyl)-1,2,4-triazole-5-[(a-thioacetyl)
-aminobenzoyl]-D,L-phenylglycine (V);
 3-[(5’-nitro-1H-indazole-1’-yl)-methyl]-4-(p-methoxyphenyl)-1,2,4-triazole-5-
[(a-thioacetyl)-aminobenzoyl]-D,L-phenylglycine (VI);
 3-[(5’-nitro-1H-indazole-1’-yl)-methyl]-4-phenyl-1,2,4-triazole-5-[(a-thioacetyl)-
aminobenzoyl]-L-phenylalanine (VII);
 3-[(5’-nitro-1H-indazole-1’-yl)-methyl]-4-(p-tolyl)-1,2,4-triazole-5-[(a-thioacetyl)-
aminobenzoyl]-L-phenylalanine (VIII);
 3-[(5’-nitro-1H-indazole-1’-yl)-methyl]-4-(p-methoxyphenyl)-1,2,4-triazole-5-
[(a-thioacetyl)-aminobenzoyl]-L-phenylalanine (IX).

This is a simple and efficient procedure used in the reaction of 3-[(5’-nitro-1H-inda-

zole-1’-yl)-methyl]  4-phenyl-1,2,4-triazole-sulfur-acetic with p-aminobenzoyl-DL-phe-
nylglycine and p-aminobenzoyl-phenylalanine. About this procedure the information
from literature is limited. The reaction of esters’ condensation with the two amino acid
derivatives, although very simple, proved as being hardly controlled due to the reduced
reactivity of the amino group. The sulfur acetic esters reactivity and the purity of the
amino acid derivatives have a decisive influence on the synthesis efficiency in obtaining
the final products, 3-[(5’-nitro-1H-indazole-1’-yl)-methyl]  4-phenyl-1,2,4-triazole-5’-
(a-tioacetyl)-peptides.
The structure of the synthetized new compounds (IV-IX) was established by chemical
analysis (Table 1), and spectral analysis - FTIR (Table 2) and NMR (Table 3). The
obtained results given in Table 1 are in the limits of the admissible experimental errors.
The structure of compounds IV-IX was also confirmed by FTIR analysis (see Table 2).
The FTIR spectra all display characteristic bands of NH group at 2822–3408 cm1.
Absorption bands between 1613–1342 cm1 are attributed to carbonyl amidic group and
those between 1335–1342 cm1 and 1516–1582 cm1 to NO2 group. A supplemental
absorption band attributed to methoxy group appears at 1107 cm1 and 1109 cm1, in
FTIR spectra of compounds VI and IX, respectively. The absorption band attributed to

Table 1. Characteristics of compounds IV-IX.

Elemental analysis
C (%) H (%) N (%) S (%)
Compound Formula 0
M. p. ( C) î(%) Calc. Exp. Calc. Exp. Calc. Exp. Calc. Exp.
IV C33H26N8O6S 212-214 87 59.77 60.18 3.92 4.18 16.91 17.32 4.83 5.19
V C34H28N8O6S 218-220 82 60.35 60.54 4.14 4.45 16.56 16.95 4.73 5.12
VI C34H28N8O7S 230-232 79 58.95 59.14 4.04 4.37 16.18 16.45 4.62 5.02
VII C34H28N8O6S 215-216 84 60.35 60.73 4.14 4.43 16.56 16.92 4.73 5.08
VIII C35H30N8O6S 225-226 80 60.85 61.08 4.34 4.51 16.23 16.57 4.63 5.03
IX C35H30N8O7S 234-235 78 59.49 59.80 4.24 4.51 16.36 16.26 4.53 4.86
 MOLECULAR CRYSTALS AND LIQUID CRYSTALS 101

Table 2. Attribution and wavenumber (cm-1) of FTIR bands of compounds IV-IX.

Compound Characteristic IR absorption bands
IV 688 (C-S); 785 (S-CH2); 815, 897 (di-substituted benzene ring); 1072 (C-N-C); 1335 (NO2 symmetric);
1573 (NO2 asymmetric); 1613 (C ¼ O amide); 1619 (C ¼ C); 2822, 2917 (NH); 3242 (COOH)
V 688 (C-S); 790 (S-CH2); 818 (di-substituted benzene ring); 1070 (C-N-C); 1335 (NO2 symmetric); 1518
(NO2 asymmetric); 1614(C ¼ C); 1659 (C ¼ O amide); 3252 (COOH); 3309 (NH)
VI 703 (C-S); 746 (S-CH2); 841, 872 (di-substituted benzene ring); 1075 (C-N-C); 1107 (Ar-OCH3); 1343
(NO2 symmetric); 1521 (NO2 asymmetric); 1634 (C ¼ C); 1688 (C ¼ O amide); 2959, 3065 (NH);
3282 (COOH)
VII 668 (C-S); 750 (S-CH2); 880 (disubstituted benzene ring); 1338 (NO2 symmetric); 1582 (NO2
asymmetric); 1067 (C-N-C); 1617(C ¼ C); 1653 (C ¼ O amide); 3093, 3309 (NH); 3268 (COOH)
VIII 688 (C-S); 790 (S-CH2); 818 (disubstituted benzene ring); 1070 (C-N-C); 1335 (NO2 symmetric); 1518
(NO2 asymmetric); 1614 (C ¼ C); 1659 (C ¼ O amide); 3252 (COOH); 3408 (NH)
IX 703 (C-S); 752 (S-CH2); 803, 821 (disubstituted benzene ring); 1069 (C-N-C); 1109 (Ar-OCH3); 1342
(NO2 symmetric); 1516 (NO2 asymmetric); 1616 (C ¼ C); 1681 (C ¼ O amide); 2850, 3000 (NH);
3286 (COOH)

Table 3. Signals (ppm) and their attribution in 1H NMR spectra of compounds IV-IX.
1
Compound H NMR signals in deuterated DMSO
IV 5.39 (s, 2H, CH2); 5.56-5.57 (d, 1H, CH); 5.76 (s, 2H, CH2); 6.08-6.09 (d, 2H, CHAr); 6.91-6.93 (d, 2H,
CHAr); 7.43-7.44 (m, 3H, CHAr); 7.45-7.46 (d, 2H, CHAr); 7.46-7.48 (d, 1H, CHAr); 7.81-7.83 (d, 2H,
CHAr); 7.99 (s, 1H, CHAr); 8.05 (s, 1H, NH); 8.29-8.31 (d, 1H, NH); 8.50 (s, 1H, CHAr); 8.86  8.87 (d,
1H, CHAr); 9.02 (s, 1H, CHAr); 12.66-12.68 (d,1H, COOH)
V 2.43 (s, 3H, CH3); 5.50-5.53 (d, 1H, CH); 5.69 (s, 2H, CH2); 5.69 (s, 2H, CH2); 5.83 (s, 2H, CH2); 6.57-6.59
(d, 2H, CHAr); 7.16-7.18 (d, 2H, CHAr); 7.25-7.27 (m, 3H, CHAr); 7.34-7.37 (d, 2H, CHAr); 7.40-7.42
(t, 1H, CHAr); 7.51-7.53 (m, 2H, CHAr); 7.70-7.73 (d, 2H, CHAr); 7.98 (s, 1H, NH); 8.38-8.41 (d, 1H,
NH); 8.49 (s,1H, CHAr); 8.61-8.63 (d, 1H, CHAr); 8.88 (s, 1H, CHAr); 12.72-12.74 (d, 1H, COOH)
VI 3.90 (s, 3H, OCH3); 5.45-5.47 (d, 1H, CH); 5.62 (s, 2H, CH2); 5.77 (s, 2H, CH2); 6.89  6.92 (d, 2H,
CHAr); 7.21-7.23 (d, 2H, CHAr); 7.29-7.32 (m, 3H, CHAr); 7.39-7.41 (d, 2H, CHAr); 7.44-7.46 (t, 1H,
CHAr); 7.56-7.58 (m, 2H, CHAr); 7.71-7.73 (d, 2H, CHAr); 7.80 (s, 1H, NH); 8.20-8.23 (d, 1H, NH);
8.69 (s, 1H, CHAr); 8.74-8.76 (d, 1H, CHAr); 8.80 (s, 1H, CHAr); 12.69-12.74 (d, 1H, COOH)
VII 2.90-3.20 (m, 2H, CH2); 4.50-4.60 (m, 1H, CH); 5.63 (s, 2H, CH2); 5.97 (s, 2H, CH2); 6.50-6.52 (d, 2H,
CHAr); 7.15-7.18 (t, 1H, CH2); 7.23-7.25 (m, 4H, CHAr); 7.52-7.54 (d, 2H, CHAr); 7.70 (t, 1H, CHAr);
7.86-7.88 (d, 2H, CHAr); 7.90-7.92 (d, 2H, CHAr); 8.15-8.17 (d, 1H, NH); 8.26 (s, 1H, CHAr); 8.39-8.42
(d, 1H, CHAr); 8.56-8.58 (d, 1H, CHAr); 8.70-8.74 (d, 1H, NH); 8.89 (s, 1H, CHAr ); 12.50-12.90 (d,
1H, COOH)
VII 2.11 (s, 3H, CH3); 3.10-3.30 (m, 2H, CH2); 4.99-5.06 (m, 1H, CH); 5.30 (s, 2H, CH2); 5.65 (s, 2H, CH2);
6.30-6.60 (d, 2H, CHAr); 7.06-7.09 (t, 1H, CH2); 7.19-7.22 (m, 4H, CHAr); 7.40-7.46 (d, 2H, CHAr);
7.64 (t,1H, CHAr); 7.72-7.79 (d, 2H, CHAr); 7.92-7.99 (d, 2H, CHAr); 8.23-8.25 (d, 1H, NH); 8.39 (s,1H,
CHAr); 8.60-8.65 (d,1H, CHAr); 8.69-8.72 (d,1H, NH)); 8.93 (s,1H, CHAr ); 12.21-12.40 (d,1H, COOH)
IX 2.87-2.92 (m, 2H, CH2); 3.94 (s, 3H, OCH3); 4.68-4.71 (m, 1H, CH); 5.51 (s, 2H, CH2); 5.80 (s, 2H, CH2);
6.36-6.44 (d, 2H, CHAr); 7.26-7.28 (t, 1H, CH2); 7.49-7.52 (d, 2H, CHAr); 7.79 (t, 1H, CHAr); 7.89-7.93
(d, 2H, CHAr); 8.19-8.22 (d, 1H, NH); 8.39 (s,1H, CHAr); 8.48-8.51 (d, 1H, CHAr); 8.82-8.87 (d, 1H,
NH); 8.95 (s, 1H, CHAr ); 12.87-12.95 (d, 1H, COOH)

S-CH2 appears in all FTIR spectra at 746–791 cm1 and one intense band at
815–897 cm1 is characteristic to disubstituted benzene ring. A specific band attributed
to COOH appears in FTIR at 3242–3286 cm1 (see Table 2).
The signals in IH NMR spectra of the studied compounds IV–IX are listed in
Table 3. The signals at 2.87–3.30 ppm and 5.30–5.97 ppm are attributed to protons of
CH2 group and the signals at 4.5–5.57 corresponding to the proton of the group CH
appear in all IH NMR spectra. The aromatic protons give NMR signals at
6.30–7.28 ppm, 7.43–8.39 ppm and 8.48–9.12 ppm. The protons of methyl group appear
as a singlet at 2.11–2.43 ppm in 1HNMR spectra of compounds V and VIII. The signal
at 3.90–3.94 ppm can be attributed to the protons of OCH3 group from the compounds
102 C. CHEPTEA ET AL.

Table 4. Molecular parameters of compounds IV-IX computed by SARTAN 14 software.

Parameter IV V VI VII VIII IX
Formula C33H26N8O6S C34H28N8O6S C34H28N8O7S C34H28N8O6S C35H30N8O6S C35H30N8O7S
Weight (amu) 662.687 676.714 692.713 676.714 690.741 706.740
Energy (au) 2533.081 2571.905 2646.336 2571.902 2610.719 2685.162
HOMO (eV) 8.47 8.45 8.44 8.43 8.35 8.42
LUMO (eV) 1.10 1.14 1.12 1.12 0.94 1.15
Dipole Moment (D) 12.07 13.45 13.56 11.29 11.41 11.00
PSA (Å2) 141.80 141.32 147.85 140.57 141.59 146.71
Log P 0.32 0.15 1.30 0.04 0.13 1.02
Polarizability (Å3) 89.03 90.55 91.23 90.49 92.08 92.77

Figure 1. Electrostatic charge distribution for compound (IV).

VI and IX. The singlet at 7.80–8.06 ppm and the doublet at 8.15–8.87 ppm identify the
NH amide groups. The proton of carbonyl group appears in the range 12.20–1205 ppm,
proving that the reaction of grafting the dipeptides on the triazole ring took place.
Some computed by Spartan 14 software molecular parameters are given in Table 4.
The formation energy listed in this table indicates the stability of the synthetized com-
pounds; the higher occupied molecular orbital (HOMO) and the lowest unoccupied
 MOLECULAR CRYSTALS AND LIQUID CRYSTALS 103

Figure 2. Electrostatic charge distribution for compound (VII).

Figure 3. Molecular polarizability vs. dipole moment of the studied compounds.

orbital (LUMO) give by their difference the molecular reactivity, the polar surface area
(PSA) offers information about the ability of the molecules to penetrate the cells of
human body, and logP, defined as octanol/water partition coefficient, inform us of the
hydrophylicity/lipophylicity of the studied molecules.
104 C. CHEPTEA ET AL.

Table 5. Electric charges on some molecular atoms of compounds IV-IX.

Molecule Properties IV V VI VII VIII IX
Charge on O1- in -NO2 group 0.500 0.501 0.502 0.503 0.499 0.504
Charge on O2- in NO2 group 0.494 0.493 0.494 0.495 0.499 0.496
Charge on N- from NH group next 0.826 0.800 0.789 0.794 0.799 0.768
to –C6H4–group
Charge on N- from NH group next to 0.481 0.530 0.467 0.702 0.688 0.834
phenylglycine, phenylalanine
respectively
Charge on O from C ¼ O group next to 0.627 0.618 0.620 0.624 0.627 0.617
–CH2–S group
Charge on O2 from C ¼ O group next 0.577 0.620 0.580 0.620 0.629 0.627
to –C6H4– group

Figure 4. Molecular dipole moment vs. electric charge near the oxygen of NO2.

The studied compounds are dipolar (see Table 4); the compounds IV–VI are more
polar compared with the compounds VII–IX, having similar structures, but with a
group –CH2 introduced between NH group and the benzene ring. One can suppose
that the methylene group –CH2 interrupts the conjugation between p electron of –NH
group and p electrons of the aromatic nucleus.
From the Table 4 it also seen that the molecular polarizability in the first group of
molecules IV-VI is smaller that the molecular polarizability in the similar structures of
the second group VII-IX in which the atomic group –CH2 is introduced.
The negative values of LogP indicate the hydrophilic character of the majority of the
studied compounds. Only compound VIII has an lipophilic character because it has
positive computed value of LogP. Figures 1 and 2 show the electrostatic charges located
near the molecular atoms in the two studied compounds computed by Spartan 14 soft-
ware. The orientation of the electric dipole moment given by Spartan program is also
shown in these figures.
Based on the data listed in Table 4, one can establish some correlations between the
computed characteristics of the studied molecules. For example, in Figure 3 the
 MOLECULAR CRYSTALS AND LIQUID CRYSTALS 105

Figure 5. Molecular dipole moment vs. electric charge near the nitrogen atom of the first NH group.

dependence between the molecular polarizability and the electric dipole moment is
shown. The linear dependences between the molecular polarizability and dipole moment
computed by Spartan have different slopes for the groups IV-VI and VII-IX, probably
due to CH2 group introduced in the molecules of the second compounds group.
The electrostatic charges localized near the atoms in the new synthetized compound
(some of them, computed by Spartan 14, are listed in Table 5) indicate the degree of
electron charge separation in a given molecule and the molecular sites of the high abil-
ity to participate in specific interactions. The electrostatic charges localized near the
oxygen atoms of NO2 group influence the molecular dipole as it results from Figure 4,
but the slopes of the linear dependences change their signs for VII-IX group compared
with compounds IV-VI. The same tendency can be observed also for the dependence of
molecular dipole moment and the electrostatic charge on the second oxygen atom of
the same atomic group. The electric charges near nitrogen in the two (NH) groups of
molecules influence the molecular dipole moment as it is shown in Table 5. This
dependence is illustrated in the Figure 5 for the first NH group in the molecules IV-IX.
The -CH2 group introduced in VII-IX compounds also influences the dipolar
moment and polarizability. It determines an increase in the molecular polarizability and
a decrease in dipole moment, compared with molecules having a similar structure from
IV-VI group.

4. Conclusions
The aim of this research was to made the synthesis and characterization of some pepti-
des based on 5-nitroindazole. A simple and efficient procedure was used in the reaction
of 3-[(5’-nitro-1H-indazole-1’-yl)-methyl]  4-phenyl-1,2,4-triazole-sulfur-acetic with p-
aminobenzoyl-DL-phenylglycine and p-aminobenzoyl-phenylalanine.
The reaction of esters’ condensation with the two amino acid derivatives, although
very simple, proved as being hardly controlled due to the reduced reactivity of the
amino group.
106 C. CHEPTEA ET AL.

The sulfur acetic esters reactivity and the purity of the amino acid derivatives have a
decisive influence on the synthesis efficiency in obtaining the final products, 3-[(5’-
nitro-1H-indazole-1’-yl)-methyl]  4-phenyl-1,2,4-triazole-5’-(a-tioacetyl)-peptides. The
synthesis of the new compounds was followed by structural investigations like elemental
chemical analysis, spectral (FT-IR and NMR) and computational investigations.
SPARTAN 14 was used to compute some parameters of the synthesized molecules and
some linear dependences between the computed parameters and molecular characteris-
tics were evidenced. It was found that the –CH2 group introduced in the three mole-
cules of the VII-IX compounds determines the change in the sign of the slopes of the
established dependences.

Funding
This work was supported by a grant of Ministry of National Education, Project Number CNFIS-
FDI-2019-0366.

ORCID
Dana Ortansa Dorohoi http://orcid.org/0000-0003-3708-9160

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