Web of Science, ISC, CAS, Google Scholar

Document Type : Original Article


Department of Chemistry, College of Science, University of Baghdad, Baghdad, Iraq


Synthesis of a synthetic ligand (L) by mixing histidine and boric acid in molar ratios of 2:1. The complexes of transition metal were prepared by reacting CoCl2.6H2O, NiCl2.6H2O, and CuCl2.H2O with (L) in molar ratios of 2:1 (L:M). All produced compounds are investigated by using spectral methods UV-Vis, FT-IR, 1H-NMR, and AAS. In addition to the melting point, thermal analysis, magnetic susceptibility measurement, micro elemental analysis, and determination of chloride content. All complexes of transition metal were proposed to have octahedral geometries. Every component was an electrolyte as well as a paramagnetic one. All the complexes of transition metal produced were shown to be antibacterial and antifungal against the bacteria Staphylococcus aureus, Klebsiella pneumonia, and the fungus Candida. The anti-cancer activities of the ligand and copper complex were also studied.

Graphical Abstract

Synthesis of New Homogeneous Amino Acids Compound with Boron and Some of Its Metal Complexes


Main Subjects


Amino acids are chemical molecules that include both amine (-NH2) and carboxyl (-COOH) active groups, as well as a specific side chain (R group) for every amino acid [1].

The side-chain (R group) type associated with the α-carbon of amino acids varies, ranging from a single hydrogen atom in glycine to a massive heterocyclic group in tryptophan. Based on the characteristics of their side-chain, α-amino acids are typically categorized into three categories. The first group includes α-amino acids with relatively nonpolar R groups (glycine, alanine, valine, leucine, isoleucine, proline, phenylalanine, tryptophan, and methionine), the second group includes α-amino acids with uncharged but polar R groups (serine, threonine, cysteine, tyrosine, asparagine, glutamine). The third group includes charged R groups (aspartic acid, glutamic acid, lysine, arginine, and histidine) [2].

Amino acids, the building blocks of life, have long been essential in human and animal nutrition and health maintenance. This category of compounds is biochemically exceedingly essential and of considerable interest to the chemical industry due to its usefulness and the specific properties emerging from chirality. The remainder of the proteinogenic amino acids is needed in the pharmaceutical and cosmetics sectors [3].

Amino acids are also utilized as bulk biochemicals in various industrial applications to manufacture a wide range of goods, such as animal feed additives, taste enhancers in human nutrition, and components in cosmetic and medicinal products [4].

Histidine, an essential amino acid, is well known as a pH-sensitive fusogen [5]. HIS has specific chemical and metabolic features that allow it to be used as a therapy for various diseases. HIS-rich treatments provide proven advantages in organ preservation for transplantation and myocardial protection during cardiac surgery [6].

Boron compounds have been utilized to make hard glasses and glazes since prehistoric times. Boron compounds are now used in semiconductors, hard materials, and anti-cancer treatment [7]. Amino acids with B-N bonds have exceptional biological activity because of their structural and electrical characteristics: Antibacterial, insecticidal, fungicidal, herbicidal, calcium channel blocker, and antineoplastic activities [8].

This research generates the ligand by reacting histidine with boric acid. Furthermore, complexes of the transition metal of this ligand with cobalt(II), nickel(II), and copper(II) metal ions are generated to see how they affect biological function. All synthesized compounds were tested for antimicrobial effect, and anti-cancer activity was investigated for ligand and copper complex.

Materials and Methods

The Elementar Analysensysteme GmbH recorded elemental microanalyses (CHN) for carbon, hydrogen, and nitrogen. Using the Gallenkamp melting point apparatus, the melting points were determined. The FT-IR (Fourier Transform Infrared) spectrophotometry for the ligand (400-4000) cm-1 (KBr) as well as complexes (250- 4000) cm-1 (CsI). Ultra Violet UV-Visible spectra were acquired in the (240-1100) nm range using a (Shimadzu 1800-UV spectrophotometer) and H2O as a solvent. 1H-NMR spectra were collected using an Agilent Technologies 500 MHz NMR in DMSO-d6, Germany. Thermal analyses (TG and DSC) were carried out (METTLER TA 4000 SYSTEM). The metal contents were determined out by flame atomic absorption spectroscopy using Nova350 Spectrophotometer. The chloride content complexes were measured by using Mohr method.

Synthesis of the ligand [(2R)-2-amino-3-(1H-imidazol-4-yl)-1-{[(methylhydrogenio)({[(methylhydrogenio)oxy] hydrogenio})-λ^3-oxidanyl] hydrogenio} oxo) propoxy] (hydroxy)boranyl (2S)-2-amino-3-(1H-imidazol-4-yl) propanoate (L)

The synthesis of L in a 2:1 mole ratio (histidine: boric acid) by using different temperatures:

The solution of boric (0.1 g, 1.617 mmol) in 2.5 mL H2O was added to a solution of histidine (0.5018 g, 3.234 mmol) in 12 mL H2O. The mixture was stirred at room temperature for seven hrs. with TLC testing. The obtained solution was heated to evaporate part of the solvent before adding ethanol in an ice bath and crushing to precipitate the white product (Figure 1); it was rinsed with more ethanol and then dried in the oven [9, 10].

Another method for synthesis of L was used the same above method (A) except a water bath at 40-45 ºC to study the effect of moderate temperature.

Synthesis of ligand complexes with Co(II), Ni(II), and Cu(II)

Synthesis of complexes in 2:1 (L: M) mole ratio

The mixture solutions of ligand and metal salts in H2O were heated via reflux for five hrs. with stirring. Table 1 show the synthesis conditions for the complexes. The obtained solution was heated to evaporate a portion of the solvent before adding ethanol in the presence of an ice bath and crushing to precipitate the compounds; it was rinsed with more ethanol and then dried in the oven.

Biological evaluation (Anti-microbial activity)

All synthesized compounds were tested for anti-bacterial and anti-fungal activity against [gram-positive Staphylococcus aureus, gram-negative Klebsiella pneumonia, and Candida] using the diffusion technique using 2×10-2 M in H2O solutions. The diameters of inhibition were evaluated to determine anti-bacterial activity.

Results and Discussion

The physical characteristics, as well as the elemental analysis data illustrated in (Table 2) and also more names and chemical formulas are presented in (Table 3).

FT-IR spectroscopy

The spectra of complexes exhibited shifting in ν(NH2) (Table 4) due to coordination with metals through the nitrogen atom of NH2 [11, 12]. The peaks that appeared at 3122-3230 cm-1 were assigned to lattice water, but coordinated water showed peaks at a region between 904-925 cm-1 [13]. 

The band of ν(-NH) (imidazole group) appeared between 3000-3014 cm-1 [14]. The band of C=N cyclic in the imidazole ring was moved in the spectra to a higher frequency of complexes because of the participation in complexation with metal ions via lone pair of the nitrogen atom in the imidazole ring [15, 16].

Finally, new bands appeared at lower frequencies which were assigned to υ (M- N) and υ (M-Cl) [17, 18], as shown in Table 4.

Figure 2 represents the general form of complexes, and Figures 3, 4, 5, and 6 refer to charts of IR for ligands and their complexes.

1H-NMR spectroscopy

The 1H-NMR spectrum of ligand (L) showed a signal at δ 2.5 ppm that belongs to the chemical shift of the solvent DMSO, and the peak at δ 3.2 ppm attributed to H2O protons as impurity [19]. The chemical shift position and assignments of all peaks were illustrated in (Table 5) for L depending on Figure 7. The chemical shift of NH (imidazole ring) showed at 11.98 ppm (broad) for L shown in Figure 8.

Thermal analysis of the ligand and its metal complexes

The analysis of TG and DSC with argon gas at the temperature range 0-800 °C (10 °C/min). This technique is used to investigate thermal stability and characterize produced chemicals. Thermal dissociation data is given in Table 6 and the thermographs of ligand and its metal complexes are shown in Figure 9, 10, 11 and 12.

Electronic spectra and magnetic measurement

At room temperature in H2O, the electronic spectra of the generated compounds were measured (10-3M).

Electronic spectrum of ligand

The electronic spectra of the ligand showed a high-intensity band at 204 nm (49019 cm-1) (Table 7) due to the π -π* transition [27-29]. The ligand spectrum is depicted in Figure 13.

Electronic spectrum of Cobalt(II) complex (C1)

As a result of coordination with a metal ion, the spectra of the C1 complex (Figure 14) exhibited a shift in the location of the π-π* transition. The spectra of the C1 complex showed bands at 675 nm (14814 cm-1) and 960 nm (10416 cm-1) that were ascribed to the 4T1g(F)4A2g(F) and 4T1g→4T2g transitions of the octahedral Co(II) complex [30, 31].

Electronic spectrum of Ni(II) complex (C2)

The spectrum of the C2 complex (Figure 15) revealed a shift in the location of π-π* transition due to coordination with metal ions. The spectrum of the C2 complex was shown, with bands appearing at 345 nm (28985 cm-1), 680 nm (14705cm-1), and 961nm (10405) cm-1, these bands assigned to 3A2g→3T1g(P), 3A2g→3T1g and 3A2g→3T2g transition respectively of octahedral Ni(II) complex [32].

Electronic spectrum of Cu(II) complex (C3)

The spectrum of the C3 complex (Figure 16) showed a change in the position of π-π* transition due to coordination with metal ions. The spectrum of the C3 complex was shown, with bands appearing at [{606 nm (16501 cm-1), 679nm (14727 cm-1)} average equal 640nm (15614 cm-1) and 961nm (10405) cm-1], these bands assigned to 2B1g → 2B2g and 2B1g→2A1g transition respectively of octahedral Cu(II) complex [33, 34].

A complex structure was determined using magnetic susceptibility (μeff). The intensity of complicated ligand fields and the number of unpaired electrons are included in this measurement. The magnetic field of spin (μs)
 for all complexes is described by the spin quantum number (s) according to the following:

S = n/2 (n= unpaired electrons number)

The magnetic moment of Co(ΙΙ) complex 4.56 was paramagnetic and indicated to octahedral geometry for C1 [35]. The magnetic moment was 3.34 for Ni(ΙΙ) complex, indicated octahedral geometry for C2 and paramagnetic properties [32]. The magnetic moment was 2.23 for Cu(ΙΙ) complex, indicated to octahedral geometry for C3 and paramagnetic properties [32].

Complex conductivity measurements in H2O found that every complex (C1-C3) is an electrolyte. The values of molar conductivity in H2O were determined. 142, 142, and 117 (S.cm2.mol-1), suggesting a C1, C2, and C3 complex electrolyte in a 1:1 ratio [36].

Biological activity (Antimicrobial activity)

The behavior of the synthesized compounds as antibacterial and antifungal was evaluated against gram-positive bacteria Staphylococcus aureus, gram-negative bacteria Klebsiella pneumonia, and Candida. The results indicated that L has more activity than histidine in Staphylococcus aureus, according to the following activity order (boric acid > L > histidine) depending on inhibition zone (23 > 19 > 13) mm. respectively. In Klebsiella pneumoniae, according to the following order, boric acid has higher activity (boric acid > histidine > L) depending on the inhibition zone (20 > 15 > 10) mm. respectively.

Comparison of the biological activities in Staphylococcus aureus of L and its metal complexes was in the following order (C2 > C1 > C3 > boric acid > L > histidine) at the inhibition zone (36 > 30 > 28 > 23 > 19 > 13) mm and in Klebsiella pneumonia the complexes were more energetic than L and the order was as following (C1 ~ C3 > boric acid > histidine > C2 > L) depending on inhibition zone (26 ~ 25 > 20 > 15 > 12 > 10) mm, respectively.

Table 8 shows the antibacterial and antifungal dates results, while Figures 17, 18 and 19 show the inhibition zones.

Anticancer activity

The cytotoxic impact of the ligand and complex on ovarian cancer cells (SKOV3) was investigated using the 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) test technique (Figures 20 and 21) (Table 9). From the above results, it is clear that the ligand has a higher effect against ovarian cancer than the copper complex due to the association of the active sites in the ligand with the transition element Cu.


By combining histidine with boric acid in a 2:1 molar ratio, a fresh ligand (L) was generated. Metal complexes, including cobalt(II), nickel(II), and copper(II), were produced in a 2:1 (L: M) molar ratio. All the molecules created were examined, and the proposed structure was confirmed using spectral and physico-chemical methods. The results showed the octahedral geometry of cobalt(II), nickel(II), and copper(II) complexes and have an electrolyte character. The biological results showed that all the synthesized compounds possessed excellent antimicrobial activity against gram-positive bacteria Staphylococcus aureus, gram-negative Klebsiella pneumoniae, and fungi Candida. The ligand and copper complex that was created had anti-cancer activity, with the ligand being more active than the complex.


This is a study requirement for the Ph.D. degree for researcher Fiadh A. Neshan.


This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Authors' contributions

All authors contributed to data analysis, drafting, and revising of the paper and agreed to be responsible for all the aspects of this work.

Conflict of Interest

We have no conflicts of interest to disclose.


Hiba Modar Shihab


Supporting Information

Copies of 1H-NMR spectrum of the ligand (L), Cytotoxicity of (L) towards SKOV3, and Cytotoxicity of C3 (Cu complex) towards SKOV3 (pdf).



Hiba Modar Shihab, Asmaa Mohammed Noori Khaleel. Synthesis of New Homogeneous Amino Acids Compound with Boron and Some of Its Metal Complexes. Chem. Methodol., 2023, 7(2) 137-155


URL: http://www.chemmethod.com/article_160597.html

[1]. Bastings J.J., van Eijk H.M., Olde Damink S.W., Rensen S.S., "d-amino Acids in Health and Disease: A Focus on Cancer," Nutrients, 2019, 11:2205 [Crossref], [Google Scholar], [Publisher]
[2]. Vig B.S., Huttunen K. M., Laine K., Rautio J., "Amino acids as promoieties in prodrug design and development", Advanced Drug Delivery Reviews, 2013, 65:1370 [Crossref], [Google Scholar], [Publisher]
[3]. Leuchtenberger W., Huthmacher K., Drauz K., "Biotechnological production of amino acids and derivatives: current status and prospects", Applied microbiology and biotechnology, 2005, 69:1 [Crossref], [Google Scholar], [Publisher]
[4]. D'Este M., Alvarado-Morales M., Angelidaki I., "Amino acids production focusing on fermentation technologies–A review", Biotechnology advances, 2018, 36:14 [Crossref], [Google Scholar], [Publisher]
[5]. Raja M.A., Arif M., Feng C., Zeenat S., Liu C.G., "Synthesis and evaluation of pH-sensitive, self-assembled chitosan-based nanoparticles as efficient doxorubicin carriers", Journal of Biomaterials Applications, 2017, 31:1182 [Crossref], [Google Scholar], [Publisher]
[6]. Holeček M., "Histidine in health and disease: metabolism, physiological importance, and use as a supplement," Nutrients, 2020, 12:848 [Crossref], [Google Scholar], [Publisher]
[7]. Khaleel A.M.N., Jaafar M.I., "Synthesis and characterization of boron and 2-aminophenol Schiff base ligands with their Cu (II) and Pt (IV) complexes and evaluation as antimicrobial agents," Oriental Journal of Chemistry, 2017, 33:2394 [Crossref], [Google Scholar], [Publisher]
[8]. Başeren Ş.C., Erdoğmuş A., Gül A., "Synthesis and boron interaction of new amino acid containing phthalocyanines and the precursor," Journal of Organometallic Chemistry, 2018, 866:105 [Crossref], [Google Scholar], [Publisher]
[9]. Sizir U., Kose D.A., Yurdakul O., Synthesis, spectroscopic and thermal characterization of non-metal cation nmc pentaborates salts containing 2-amino-5-nitropyridine and 2-amino-6-methylpyridine as cation, Hittite Journal of Science and Engineering, 2015, 2:91 [Crossref], [Google Scholar], [Publisher]
[10]. Khan S.A., Nami S.A., Bhat S.A., Kareem A., Nishat N., Synthesis, characterization and antimicrobial study of polymeric transition metal complexes of Mn (II), Co (II), Ni (II), Cu (II) and Zn (II), Microbial pathogenesis, 2017, 110:414 [Crossref], [Google Scholar], [Publisher]
[11]. Garza-Ortiz A., Camacho-Camacho C., Sainz-Espuñes T., Rojas-Oviedo I., Gutiérrez-Lucas L.R., Gutierrez Carrillo A., Vera Ramirez M.A., Novel organotin (IV) schiff base complexes with histidine derivatives: Synthesis, characterization, and biological activity, Bioinorganic Chemistry and Applications, 2013, 2013:502713 [Crossref], [Google Scholar], [Publisher]
[12]. Bougherra H., Berradj O., Adkhis A., Amrouche T., "Synthesis, characterization, electrochemical and biological activities of mixed ligand copper (II) complexes with dimethylglyoxime and amino acids," Journal of Molecular Structure 2018, 1173:280 [Crossref], [Google Scholar], [Publisher]
[13]. Neamah A.A., Khaleel A.M.N., " Synthesis of New Schiff Base from Antibiotics and Some of Its Metal Complexes with Study Some of Their Applications," Chemical Methodologies, 2022, 6:372 [Crossref], [Google Scholar], [Publisher]
[14]. Trivedi M.K., Branton A., Trivedi D., Nayak G., Saikia G., Jana S., "Physical and structural characterization of biofield treated imidazole derivatives", Natural Products Chemistry & Research, 2018, 3:1000187 [Crossref], [Google Scholar], [Publisher]
[15]. Mahmoud W.H., Omar M.M., Sayed F.N., Mohamed G.G., "Synthesis, characterization, spectroscopic and theoretical studies of transition metal complexes of new nano Schiff base derived from l‐histidine and 2‐acetylferrocene and evaluation of biological and anticancer activities," Applied Organometallic Chemistry, 2018, 32:e4386 [Crossref], [Google Scholar], [Publisher]
[16]. Khaleel A.M.N., "Synthesis Of Tripodal Borate Ligand With Ni(Ii) And Cu(Ii) Complexes," International Journal of Applied Sciences and Technology, 2015 [Crossref], [Google Scholar], [Publisher]
[17]. Al-Jebouri G.S., Khaleel A.M.N., "Synthesis of New Boron Compounds with Amoxicillin and Some of Its Metal Complexes with Use Them in Antibacterial, Assessment of Hepatoprotictive and Kidney activity, Anticancer and Antioxidant Applications," Journal of Pharmaceutical and Clinical Research, 2019, 12:496 [Crossref], [Google Scholar], [Publisher]
[18]. Reshma R., Selwin Joseyphus R., Arish D., Reshmi Jaya R.J., Johnson J., "Tridentate imidazole-based Schiff base metal complexes: molecular docking, structural and biological studies," Journal of Biomolecular Structure and Dynamics, 2021, 40:8602 [Crossref], [Google Scholar], [Publisher]
[19]. Górska-Jakubowska S., Klimaszewska M., Podsadni P., Kaleta B., Zagożdżon R., Górska S., Gamian A., Strączek T., Kapusta C., Cieślak M., Kaźmierczak-Barańska J., Selenium-Containing Exopolysaccharides Isolated from the Culture Medium of Lentinula edodes: Structure and Biological Activity, International Journal of Molecular Sciences, 2021, 22:13039 [Crossref], [Google Scholar], [Publisher]
[20]. Neelakantan M.A., Sundaram M., Nair M.S., "Synthesis, spectral and thermal studies of some transition metal mixed ligand complexes: Modeling of equilibrium composition and biological activity," Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2011, 79:1693 [Crossref], [Google Scholar], [Publisher]
[21]. Zhang S., Zhang M., Xing J., Lin S., "A possible mechanism for enhancing the antioxidant activity by pulsed electric field on pine nut peptide Glutamine‐Tryptophan‐Phenylalanine‐Histidine," Journal of food biochemistry, 2019, 43:e12714 [Crossref], [Google Scholar], [Publisher]
[22]. Sheveleva N.N., Markelov D.A., Vovk M.A., Tarasenko I.I., Mikhailova M.E., Ilyash M.Y., Neelov I.M., Lahderanta E., "Stable deuterium labeling of histidine-rich lysine-based dendrimers," Molecules, 2019, 24:2481 [Crossref], [Google Scholar], [Publisher]
[23]. Fu R., Miao Y., Qin H., Cross T.A., "Observation of the imidazole-imidazolium hydrogen bonds responsible for selective proton conductance in the influenza A M2 channel", Journal of the American Chemical Society, 2020, 142:2115 [Crossref], [Google Scholar], [Publisher]
[24]. Mamardashvili G., Kaigorodova E., Dmitrieva O., Koifman O., Mamardashvili N., "Molecular recognition of imidazole derivatives by Co (III)-porphyrins in phosphate buffer (pH= 7.4) and cetylpyridinium chloride containing solutions," Molecules, 2021, 26:868 [Crossref], [Google Scholar], [Publisher]
[25]. George D., Maheswari P.U., Begum K.M.S., "Chitosan-cellulose hydrogel conjugated with L-histidine and zinc oxide nanoparticles for sustained drug delivery: Kinetics and in-vitro biological studies," Carbohydrate polymers, 2020, 236:116101 [Crossref], [Google Scholar], [Publisher]
[26]. Gao S., Liu Y., Feng S., Lu Z., "Synthesis of borosiloxane/polybenzoxazine hybrids as highly efficient and environmentally friendly flame retardant materials," Journal of Polymer Science Part A: Polymer Chemistry, 2017, 55:2390 [Crossref], [Google Scholar], [Publisher]
[27]. Shahabadi N., Moeini N., "Synthesis, characterization and DNA interaction studies of a new platinum (II) complex containing caffeine and histidine ligands using instrumental and computational methods," Journal of Coordination Chemistry, 2015, 68:2871 [Crossref], [Google Scholar], [Publisher]
[28]. Godlewska S., Jezierska J., Baranowska K., Augustin E., Dołęga A., "Copper (II) complexes with substituted imidazole and chlorido ligands: X-ray, UV–Vis, magnetic and EPR studies and chemotherapeutic potential," Polyhedron, 2013, 65:288 [Crossref], [Google Scholar], [Publisher]
[29]. Rogala P., Jabłońska–Wawrzycka A., Kazimierczuk K., Borek A., Błażejczyk A., Wietrzyk J., Barszcz B., "Synthesis, crystal structure and cytotoxic activity of ruthenium (II) piano-stool complex with N, N-chelating ligand," Journal of Molecular Structure, 2016, 1126:74 [Crossref], [Google Scholar], [Publisher]
[30]. Ali F.J., Radhi E.R., Ali K.J., "Synthesis and Characterization of a New Azo Ligand Derivative from 4, 5-BIS (4-Methoxyphenyl) Imidazol and its Metal Complexes and Biological Activity Study of its PD (II) Complex," Pakistan Journal of Medical & Health Sciences, 2022, 16:431 [Crossref], [Google Scholar], [Publisher]
[31]. Rahmouni N.T., el Houda Bensiradj N., Megatli S.A., Djebbar S., Baitich O.B., "New mixed amino acids complexes of iron (III) and zinc (II) with isonitrosoacetophenone: Synthesis, spectral characterization, DFT study and anticancer activity," Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2019, 213:235 [Crossref], [Google Scholar], [Publisher]
[32]. Abdul-Ghani A.J., Khaleel A., "Synthesis and characterization of new schiff bases derived from N (1)-substituted isatin with dithiooxamide and their co (II), Ni (II), Cu (II), Pd (II), and Pt (IV) complexes," Bioinorganic Chemistry and Applications, 2009, 2009:413175 [Crossref], [Google Scholar], [Publisher]
[33]. Abdulghani A.J., Khaleel A.M.N., "Preparation and characterization of Di-, Tri-, and tetranuclear Schiff base complexes derived from diamines and 3, 4-dihydroxybenzaldehyde," Bioinorganic chemistry and applications, 2013, 2013:219356 [Crossref], [Google Scholar], [Publisher]
[34]. Arunadevi A., Paulpandiyan R., Raman N., "DNA interaction, molecular docking and biological profile of tetradentate histidine based metallointercalators," Journal of Molecular Liquids, 2017, 241:801 [Crossref], [Google Scholar], [Publisher]
[35]. Abdulghani A.J., Abbas N.M., "synthesis characterization and biological Activity study of New Schiff and mannich bases and some metal complexes derived from isatin and dithiooxamide," Bioinorganic chemistry and applications, 2011, 2011:706262 [Crossref], [Google Scholar], [Publisher]
[36]. Geary W.J., "The use of conductivity measurements in organic solvents for the characterisation of coordination compounds," Coordination Chemistry Reviews, 1971, 7:81 [Crossref], [Google Scholar], [Publisher]