Journal of Molecular Liquids 224 (2016) 914–929
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Journal of Molecular Liquids journal homepage: www.elsevier.com/locate/molliq
Spectroscopic behavior and equilibrium studies of some metallocephalosporins Mamdouh S. Masoud a, Alaa E. Ali b,⁎, Doaa A. Ghareeb c, Nessma M. Nasr d a
Chemistry Department, Faculty of Science, Alexandria University, Alexandria, Egypt Chemistry Department, Faculty of Science, Damanhour University, Damanhour, Egypt Biochemistry Department, Faculty of Science, Alexandria University, Alexandria, Egypt d University Student's Hospital, Alexandria University, Alexandria, Egypt b c
a r t i c l e
i n f o
Article history: Received 10 August 2016 Accepted 29 September 2016 Available online 2 October 2016 Keywords: Dissociation constants Cephradine Cefepime Spectrophotometric Potentiometric measurements Regression analysis Solvent parameters Kamlet–Taft solvent parameters
a b s t r a c t The dissociation constants of cephradine, cefepime were evaluated at room temperature by spectrophotometric and potentiometric measurements. Also, the dissociation constants of their complexes with iron (III) nickel (II) and copper (II) in the presence of water and different percentages of ethanol–water media were calculated potentiometry. Regression analysis is applied for correlating the different parameters based on an equation that relates the wavenumbers of the absorption band maxima (υmax) to the solvent parameters; refractive index (n), dielectric constant (D), empirical Kamlet–Taft solvent parameters, π*(dipolarity/polarizability), α (solvent hydrogen-bond donor acidity) and β (solvent hydrogen-bond acceptor basicity) by using the SPSS program. The results help to assign the solute-solvent interactions and the solvatochromic potential of the investigated compounds. © 2016 Elsevier B.V. All rights reserved.
1. Introduction Cephalosporins are β-lactam antibiotics differ from the penicillins in B ring, which is a 6-membered dihydrothiazine ring [1-4]. Variations among the cephalosporins are made on either the acyl side chain at the 7-position to change antibacterial activity or at the 3-position to alter the pharmacokinetic profile [5–6]. The cephalosporins inhibit bacterial cell wall synthesis by blocking the transpeptidases [7–9]. Cephalosporins are classified into five generations. The first generation is most active against aerobic Gram-positive cocci and includes cephradine, cefazolin, cephalexin and cefadroxil and they are often used for skin infections caused by S. aureus and Streptococcus. They have activity against E. coli and some activity against H. influenzae and Klebsiella species, but because of the limited gram-negative coverage, they are not first-line agents for infections that are likely to be caused by Gram-negative bacteria [10], while the second generation active against Gram-negative organisms, such as Moraxella, Neisseria, Salmonella, and Shigella. Cefoxitin and cefotetan, also have more coverage against anaerobic bacteria. The true cephalosporins that are also part of this class are cefprozil, cefuroxime, cefaclor, cefoxitin, and cefotetan. These drugs are used primarily for respiratory tract infections because they are better against some strains of beta-lactamase producing H. influenza [10]. However ⁎ Corresponding author. E-mail address:
[email protected] (A.E. Ali).
http://dx.doi.org/10.1016/j.molliq.2016.09.116 0167-7322/© 2016 Elsevier B.V. All rights reserved.
the third have the most activity against Gram-negative organisms, including Neisseria species, M. catarrhalis, and Klebsiella, while ceftazidime is active against P. aeruginosa. These agents have less coverage of the Gram-positive cocci, notably methicillin-sensitive S. aureus. In addition to the agent with antipseudomonas coverage, this class includes cefdinir, cefditoren, cefixime, cefotaxime, cefpodoxime, ceftibuten, and ceftriaxone. These drugs are useful for more severe community-acquired respiratory tract infections, resistant infections, and nosocomial infections (because of the high incidence of resistant organisms) [10]. Cefepime is involved in fourth generation class because it has good activity against both Gram-positive and negative bacteria, including P. aeruginosa and many Enterobacteriaceae. The Gram-negative and anaerobic coverage made cefepime useful for intra-abdominal infections, respiratory tract infections, and skin infections [10]. Ceftaroline fosamil is fifth generation cephalosporin; it has enhanced activity against many both Gram-negative and positive bacteria. It is active against community-acquired pneumonia infections caused by E. coli, H. influenzae, Klebsiella, S. aureus (methicillin-susceptible isolates only), and S. pneumoniae and safe for treating skin infections caused by multidrugresistant S. aureus [11–14]. In the present study UV spectrometry and potentiometry were used in order to determine and characterize the dissociation constants of cephradine, cefepime and their complexes. Also, the solvent effects on electronic absorption spectra of cephradine, cefepime and their complexes were assigned. A linear correlation was adopted to indicate the solvatochromic behavior between experimental
M.S. Masoud et al. / Journal of Molecular Liquids 224 (2016) 914–929
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spectral values and solvent parameters to evaluate their contributions to the solute-solvent interactions. 2. Experimental Antibiotics (cephradine and cefepime) are obtained from Pharcopharmaceutical Company. The solvents (chloroform, carbon tetrachloride, dimethyl sulphoxide, dimethyl formamide, dioxane, acetonitrile, acetone, ethanol and methanol) used are of Sigma Aldrich, USA, company. The UV–VIS spectra were measured with a Perkin Elmer Lamb-4B spectrophotometer. All metallocephradine and metallocefepime were synthesized as reported [15–22]. Universal buffer solution was prepared by taking 0.04 M each of H3BO3, H3PO4 and CH3COOH acids and adding the required volume of 0.2 M NaOH to give the desired pH [23]. The pH was checked by using a Jenway 3015 pH-meter, previously calibrated with standard buffer solutions of pH 4.00, 7.02 and 100.1 M KCl solutions were prepared and used to adjust the ionic strength of the solutions. Potentiometric titration was performed by Cole-Parmer instrument. The electrode system was calibrated before and after each series of pH measurements under the same conditions using standard buffers (pH's 4.0 and 7.0). The titration was recorded in presence of a purified nitrogen gas. The potentiometric titration procedure was applied to evaluate the dissociation constants of the organic compounds by introducing the appropriate volume of the organic compound into the titration cell in presence of 5 ml 0.5 M KCl solution and different percentages (v/v) of ethanol-water and 100% water media. During the whole titration, purified nitrogen gas was slowly bubbled in the solution. The same potentiometric titration experiment was applied for studying the complex equilibria (1 ml (10−2 M metal ion) + 5 ml (10−2 M ligand) + 5 ml (0.5 M KCl) + 39 ml water or different percentages (v/v) of ethanol-water and 100% water media) and titrated against standard KOH. The experiment has been carried out under the same conditions of titrating the organic compound against standard KOH. Correction of the pH-readings with a correction term δ for mixed solvents (ethanol-water) calculated by the following equation, where pHx and pHs are the values of unknown and standard buffer solutions [24]. δ ¼ pHx −pHs
ð1Þ
3. Results and discussion 3.1. Determination of the dissociation constants of cephradine and cefepime spectrometry This study is used to give spot lights on the possible species that may be formed in solutions at different pH's, to explain the acid-base behavior of such compounds. Also, the data can help to calculate the dissociation constants of the ligands. The spectra indicate that the intensity and the band positions are pH dependent with the existence of isosbestic points that has been taken as a proof of the existence of equilibria between different species usually in equilibrium with each other. Cephradine presents two maxima at 211 and 263 nm with no isosbestic point, Fig. 1, probably due to the overlapping of absorbing species, it gave three pKa values, the first pK1 attributed to the acidic (−COOH), while the second one was due to the amine and the third pKa due to the amide group, however, cefepime possess two maxima at 231 and 264 nm with two isosbestic points at 208 and 249 nm, Fig. 2, posses two pKa, the first was due to aminothiazol group and the second attributed to amide group, Figs. 3, 4. Generally, the shorter wavelength region is due to the electronic transitions (up to ~250 nm) mainly of the π-π* type, while the longer wavelength side (N225 nm) can be argued to the electronic transitions mainly of n-π* type [25], Figs. 3, 4. The ionization constants of the ligands represent the largest body of data on equilibrium constants available anywhere in the chemical literature. This can be done by different methods depending on changing the
Fig. 1. Effect of pH on the electronic absorption spectra of 4 × 10−4 M of cephradine at 261 nm.
pH of the solution and so, the absorption spectra would be changed. It was found a definite relationship between the absorbance and pH. a- Half height method [26]: The pK was evaluated at a constant wavelength from the half height of the As-pH plot, Fig. 5. It is known that: pH ¼ pK þ Log
As1 2
As max −As1
þ logγ
ð2Þ
2
where, γ = activity coefficient terms. b- Modified limiting absorption method [27]: The following equation is applied: pH ¼ pKaþ logγ þ log
Asmax −As As −Asmin
ð3Þ
where, γ is the activity coefficient term, Asmaxis the minimum absorption, Asmaxis the maximum absorption and As is the absorption at any pH. By plotting the log absorbance ratio term versus pH, a straight line is obtained. The pKa value is computed, when the log absorbance ratio value amount to zero. The data are collected in Table 1 and Fig. 6. c- Colleter method [28]: Three different concentrations of hydrogen ions are obtained from the As-pH curve and their absorbance values are given, where [H+]1 N [H+]2 N [H+]3, and A1 N A2 N A3. The acid dissociation constant
Fig. 2. Effect of pH on the electronic absorption spectra of 4 × 10−4 M of cefepime at 232 nm.
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O C CH
O S
+
C
pK1 = 2.98
NH2
NH3
N
+
NH2
NH3
CH3
O
S
+
CH
N
+
CH3
O C HO
C O
-O
O
pK2 = 7.32
O
O
C
pK3 = 10.0
S
C CH NH2
S
+ NH2
CH
HN
NH2
N
N
CH3
O
CH3
O C
C -O
-O
O
O
Fig. 3. The mode of ionization of cephradine.
is calculated as follows. M¼
K¼
þ þ A3 −A1 H 1 − H 2 : þ þ A2 −A1 H 1 − H 3
ð4Þ
þ H 2 −M H þ 3 M−1
ð5Þ
3.2. Potentiometric pH titrations for cephradine, cefepime and their complexes pKa values were determined by using acid-base titration techniques. The titration curves obtained for cephradine and cefepime are shown in
Figs. 7–8 against standard KOH in presence of 0.5 M KCl as a representative example. The application of the potentiometric measurements depends on the evaluation of the average number of the protons associated with the reagent, nA [29]. This was determined at different pH's using the simplified following equation: nA ¼ Y−
Vi N ° Vo CL
ð6Þ
where, Vi denotes the volume of alkali required to reach a given pH on the titration curve, Vo is the initial volume of the ligand, N° is the alkali concentration, CL is the total concentration of the ligand and Y is the number of displaceable hydrogen atoms in the ligand. The dissociation constants are obtained by plotting nA against pH for the free ligands.
S
S
+
H3N
+
+
H2N
N
C
C
N
O
H3N
S H3C N
N
O
H3CO
+
H2N
N
pK 1 = 2.37 Not detected
C
S
C
H3C N
O
N
N
O
H3CO O
HO
O
-O
pK 2 = 3.02 S S
H2N
HN N
C N
H3CO
S
H2N
C
H3C N
O
N
pK 3 = 10.80
+
N
O H3CO -O
H2N C
C
N
O
S H3C N
N
O
O -O Fig. 4. The mode of ionization of cefepime.
O
M.S. Masoud et al. / Journal of Molecular Liquids 224 (2016) 914–929
917
ligand present. It follows that in the low pH buffer region: CA ¼ ½H2 A þ bHA− c
ð11Þ h
aCA þ Hþ ¼ ½HA− þ A2− K1 ¼
i
ð12Þ
þ H aCA þ Hþ þ CA − aCA þ H
ð13Þ
In the high pH buffer region, the concentration of the acid from (H2A) of the ligand is neglected and so: K2 ¼ Fig. 5. Absorbance-pH profile for cephradine and cefepime.
Two pK's values were obtained for ligands by recording the pH values at nA = 0.5 and 1.5 (pK1 and pK2, respectively). The point-wise calculation [30] was used for the same purpose, where concordant results are obtained. pH ¼ log
nA −1 þ pK1 2−nA
ð7Þ
pH ¼ log
nA þ pK2 1−nA
ð8Þ
H2 A↔Hþ þ HA− k1 ¼ Hþ ½HA− =½H2 A
ð9Þ
i h k1 ¼ Hþ A2− =½HA−
ð10Þ
H2A represents the ligands and parentheses represent the molar concentrations. Since K1 N K2, each dissociation stage was considered separately. If CA represents the total concentration of the ligand species and “a” represents the number of moles of base added per mole of the
ð14Þ
The titration curves indicated a diprotic acid profile; the first pKa of cephradine is due to the amine and the other pKa due to the amide group, while cefepime gave two pKs, the first one is due to two overlapping ionization constants (the acidic (− COOH) and aminothiazol group) and pk2 is due to the amide group. The pK values of the investigated antibiotics are dependent upon both the nature and the proportion of the organic cosolvent. In general, increasing the organic cosolvent content in the medium results in an increase in the pK value. However, the acidity constants in a pure aqueous medium (Ka1) can be related to that in water-organic solvent mixtures (Ka2) by Eq. (15) [32]: Ka1 ¼ Ka2
A basic method of calculation of dissociation constants for ligands constructed by Martell [31], where the equilibrium involved as follows:
HA− ↔Hþ þ A2−
þ H ðða−1ÞCA −½OH− Þ ð2−aÞCA −½OH−
γHþ γA− γHA
ð15Þ
The γ is the activity coefficient of the subscripted species in a partially aqueous medium to that in a pure aqueous one. Since it is known that the electrostatic effects of solvents operate only on the activity coefficients of charged species [33], one can expect that the increase in the amount of the organic cosolvent in the medium will increase the activity coefficients of both H+ and A− ions. This decreased the acid dissociation constant (high pK value). By comparing the pH titrations of the free ligands to that of the complex solutions, drop of the pH values occurs assuming that the mechanism of complexation is based on hydrogen ion liberation. The pK values of the free ligands are strongly affected on complexation. The
Table 1 Dissociation constants for the organic compounds spectrophotometrically. Compound
Cephradine Cefepime
Half height
Modified limiting method
Colleter
pK1
pK2
Pk3
pK1
pK2
Pk3
pK1
pK2
Pk3
pK1
Average pK pK2
Pk3
3.04 3.04
7.0 10.5
10.0 –
2.8 3.1
7.9 10.7
10.0 –
3.04 3.15
7.0 11.0
10.0 –
2.98 ± 0.1 3.2 ± 0.15
7.32 ± 0.5 10.76 ± 0.2
10.0 ± 0.0 –
Fig. 6. Modified limiting absorption method curves for: A-Cephradine, B-Cefepime.
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(A) pH- titration for 0.01 M cephradine in presence of 100% water, 25% and 75%ethanol (v/v).
(B) n A – pH relationship for 0.01 M cephradine in presence of 100% water, 25% and 75% ethanol (v/v).
(C) Point- wise plot for 0.01 M cephradine in presence of 100% water, 25% and 75% ethanol v/v)
(D) Distribution of species of cephradine. Fig. 7. Potentiometric titration curves and chemical speciation for cephradine.
measurements during titration of the solution of chelating agent in presence and in absence of metal ions with alkali could be used to calculate the free ligand exponent pL, the degree of formation of the system n and hence the stability constants of the metal ligand complexes present. n¼
n¼
n¼
Total concentration of the ligand bound to the metal Total concentration of the metal
ð16Þ
C L −concentration of the ligand not bounded to the metal CM
ð17Þ
CL − CH þ Hþ =n CM
ð18Þ
The CL and CM are the analytical concentrations of the ligand and metal, respectively. Plotting the n values versus pL, values at n equals to 0.5 and 1.5 respectively. Table (2) gave the corresponding pK values. Concordant results were obtained on applying the point-wise calculation method [30–33] and the distribution of species at different pH. pL þ log
n ¼ logK1 ; nb1 1−n
ð19Þ
pL þ log
n−1 − logK2 ; 1bnb2 2−n
ð20Þ
It was noticed that, pKa values in case of metal complexes were decrease, this may be due to the metal ion is considered as an electrophilic
M.S. Masoud et al. / Journal of Molecular Liquids 224 (2016) 914–929
(A) pH- titration for 0.01 M cefepime in presence of 100% water, 25% and 75% ethanol (v/v).
919
(B)
n A – pH relationship for 0.01 M cefepime in presence of 100% water, 25% and 75% ethanol (v/v).
(C) Point- wise plot for 0.01 M cefepime in presence of 100% water, 25% and 75% ethanol (v/v).
(D) Distribution of species of cefepime. Fig. 8. Potentiometric titration curves and chemical speciation for cefepime.
site, so the hydrogen ion is easily migrate leading to decrease pKa values [34–39]. 3.3. Solvatochromic behavior of investigated compounds 3.3.1. Solvent effects on the UV-Vis absorption spectra The electronic absorption spectra of cephradine, cefepime and their metal complexes were shown in Tables 3–4 and Fig. 9 is a representative example for the electronic absorption spectra for cephradine and cefepime. For cephradine and its metal complexes, the high energy bands of π-π* transition at 192–256 nm in hydrogen bonding solvents (e.g. propanol, ethanol, methanol and water) are due to the presence of an external hydrogen bond affecting the k-band [40], while the low lying
n-π* electronic transition in the wavelength range 260–363 nm is present in all solvents used. The blue shift of these bands especially in case of polar or hydrogen bonding solvents like H2O, methanol and ethanol are due to the hydrogen bond formation probably takes place between the solute and the solvent through the hydroxyl group. This leads to the existence of some chromophoric groups, thus the π-system is stabilized and tends to lower the energy of the ground state and thus blue shift occurs with increasing the solvent polarity [41]. However, in case of cefepime and its metal complexes, the slight shift of λmax of the electronic spectral bands from alcohol (propanol, ethanol and methanol) to H2O, depicts the presence of an internal hydrogen bond affected by the interaction with n-electrons blocked by the solvent leading to increase localization of electrons [42]. The
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Table 2 pK values for cephradine, cefepime and their complexes potentiometrically. nA -pH
Antibiotics
Cephradine
Cefepime
Fe-cephradine complex (1:1)
Ni-cephradine complex (1:1)
Cu-cephradine complex (1:1)
Fe-cefepime complex (1:1)
Ni-cefepime complex (1:1)
Cu-cefepime complex (1:1)
100% water 25% ethanol 75% ethanol 100% water 25% ethanol 75% ethanol 100% water 25% ethanol 75% ethanol 100% water 25% ethanol 100% water 100% water 25% ethanol 75% ethanol 100% water 25% ethanol 75% ethanol 100% water 25% ethanol 75% ethanol 100% water 25% ethanol 75% ethanol
Point-wise method
Average
pK1
pK2
pK1
pK2
pK1
pK2
7.0 7.9 7.9 5.7 5.2 5.1 4.9 5.2 5.6 5.3 5.2 5.4 5.2 5.0 5.8 4.9 5.2 5.5 4.8 5.0 4.8 5.0 5.5 5.3
9.8 10.5 10.5 10.7 10.3 10.0 8.4 8.15 8.75 8.7 8.8 9.2 8.4 8.9 9.6 8.4 8.7 8.6 8.4 8.7 8.6 8.2 8.4 8.3
7.0 7.9 8.3 5.8 5.1 5.1 4.92 5.1 5.2 5.2 5.4 5.7 5.5 5.6 6.1 5.5 5.5 5.0 5.1 5.5 5.5 5.5 5.3 5.2
9.8 10.3 10.4 10.5 10.1 9.9 8.0 8.2 8.6 8.8 8.7 9.3 8.4 8.8 9.7 8.2 8.6 8.5 8.2 8.4 8.5 8.3 8.5 8.2
7 ± 0.00 7.9 ± 0.00 8.1 ± 0.30 5.75 ± 0.07 5.15 ± 0.07 5.1 ± 0.00 4.9 + 0.00 5.15 ± 0.07 5.4 ± 0.14 5.15 ± 0.07 5.3 ± 0.14 5.55 ± 0.21 5.35 ± 0.12 5.3 ± 0.40 5.95 ± 0.21 5.2 ± 0.40 5.35 ± 0.12 5.35 ± 0.12 4.95 ± 0.21 5.35 ± 0.12 5.15 ± 0.49 5.35 ± 0.12 5.4 ± 0.14 5.25 ± 0.04
9.8 ± 0.00 10.4 ± 0.07 10.45 ± 0.07 10.6 ± 0.07 10.2 ± 0.14 9.95 ± 0.07 8.2 ± 0.14 8.17 ± 0.03 8.6 ± 0.1 8.75 ± 0.07 8.75 ± 0.07 9.25 ± 0.07 8.4 ± 0.00 8.85 ± 0.07 9.65 ± 0.07 8.3 ± 0.14 8.65 ± 0.07 8.55 ± 0.03 8.3 ± 0.13 8.55 ± 0.21 8.55 ± 0.03 8.25 ± 0.04 8.45 ± 0.04 8.25 ± 0.04
delocalized 2p orbital with the neighboring atom will necessarily be the one involved in the bond to the incoming solvents. A remarkable characteristic bands are obtained in the wavelength 190–256 nm and 260431 nm, this could be assigned to π-π* and n-π*, respectively. A further stability for these structures can be gained as a result of the enolization of the carbonyl group leading to a chelate ring structure of a six membered hydrogen bonded ring. The stability of such structures depends on the solvent and the strength of such a hydrogen bond relative to that formed between the solute and solvent molecules. The spectral features of these complexes are characterized by the following (a) the weakness of the bands (b) the large number of the bands and (c) the great variation in the widths of the bands. All these features are easily understood in terms of ligand field theory [42]. From the solvatochromism view [43], it can be negative (blue shift) induced by increasing the solvent polarity, when the ground electronic state is more stabilized compared with the excited state and vice-versa. A positive solvatochromism (red shift) appears in the case of a higher stabilization of the solute excited state, to obtain the sign (negative or positive) and the values of solvatochromism for each sample, the maximum absorption of the band recorded in presence of the most polar solvent was subtracted from that determined in the most non-polar solvent, Tables 5–6 and it was considered as spectral shift Δν is an indicator
of the red or blue spectral shifts, respectively. It was found that cephradine and its metal complexes exhibited a blue shift except Ni (1:2), Cd (2:1) and Hg (1:3) cephradine complexes showed a bathochromic shift (positive solvatochromism) as a result of an increase in the solvent polarity. Also, cefepime and its complexes (Fe (1:1), Ni (1:2), Hg (1:1), Fe Ni (1:1:3) and Co Cu (1:3:1)) showed a red shift, this effect was attributed to the interaction of solvents such as DMSO with non bonding electron pair on nitrogen atom of NH. 3.3.2. Regression analysis calculations The position of absorption bands are correlated with different solvent properties of the solvent E, M, N, K, n, D and the correlation coefficients were deduced, the following equation was applied: Y ¼ a0 þ a1 x1 þ a2 x2 þ a3 x3 þ … þ an xn
ð21Þ
where, Y is the observed peak location of an absorption band in a given solvent. a0 is the regression intercept. It has been assumed [44] to estimate of the peak position for gas phase spectra. a1, a2,…an are coefficients which could be determined by multiple regression technique.
Table 3 Electronic absorption spectra of cephradine and its metal complexes in presence of different solvents (λmax nm). Compounds
Water
Ethanol
Methanol
Propanol
Acetone ACN
Cephradine [Cr2 (Cephradine)3 (OH)3 H2O]3H2O [Mn (Cephradine) Cl (H2O)3] HCl·2H2O [Fe2 (Cephradine) Cl5 (H2O)3] H2 O [Co (Cephradine)3] 2HCl·H2O [Ni (Cephradine) Cl H2O] HCl·3H2O [Ni (Cephradine)2] 2HCl [Cu (Cephradine)2] 2HCl·6H2O [Cu3 (Cephradine) Cl5 H2O] HCl [Zn2 (Cephradine) Cl3 H2O] HCl·H2O [Cd2 (Cephradine) Cl3 H2O] HCl·H2O [Hg (Cephradine)3] 2HCl·6H2O [Fe Cu2 (Cephradine)2 Cl5 H2O] 2HCl·3H2O [Fe Co (Cephradine)2 Cl3 H2O] 2HCl·3H2O [Fe Ni (Cephradine) Cl4 (H2O)2] HCl·4H2O
260 209,275,350 226,300 192,240,300 220,350 210 205,278 200,270,350 200,270,350 200,300 210,270,350 207,275,350 221,248,330 222,249,337 238
214,263 209,275,350 211,305,350 250 209 209 – 210,275 207,276 210,302 209,275,350 208,264,325 210,254,346 209,246,349 209,238,246
212,264 222,270,356 214,300,356 215,300 226,350 232,350 238,271 – 217,276 230,300 213,271,362 220,275,350 220,252,344 215,275,349 211,336
301 214,250,350 213,317,361 250 221,370 211
334 – – – – – 252,335 – –
275 311 208,305 214,350 250,350 – 333 310
218,267 210,250,350 260,340 250,306,350 220,250,350 210,270
DMSO
215,263 275,350 260,300,350 279,350 270,350 267,365 287 226,329 275,350 226,329 275,350 215,300 300 – 223,270,363 288,375 – 250,350 300,350 211,347 259,351 269,348 – 350 284,348 210,358 231,349 265,334
DMF Dioxane
CHCl3 CCl4
274 – – – – –
268 – – – – – – – –
292 – – – – – – – –
– – – – –
– – – – –
– – – – – –
271 275,350 256,325 250,300,375 – 249,350 256,294 300 – 301 262,356 275,350 – – 208,262
M.S. Masoud et al. / Journal of Molecular Liquids 224 (2016) 914–929
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Table 4 Electronic absorption spectra of cefepime and its metal complexes in presence of different solvents (λmax nm). Compounds
Water
Ethanol
Cefepime [Cr2 (Cefepime) (OH)4 (H2O)4] OH·H2O [Mn2 (Cefepime)3 (OH)2 (H2O)2] (OH)3 [Fe (Cefepime)3] Cl3·4H2O [Fe (Cefepime) Cl2 (H2O)2] Cl·3H2O [Co2 (Cefepime) (OH)3 H2O] (OH) [Ni (Cefepime) Cl H2O] Cl·5H2O [Ni (Cefepime)2] Cl2·6H2O [Cu (Cefepime)3]2Cl·OH [Cu4 (Cefepime) Cl5 H2O] Cl·H2O [Zn (Cefepime) Cl H2O]·5H2O [Cd (Cefepime) OH H2O] OH [Hg (Cefepime)2] Cl2·6H2O [Fe Cu (Cefepime) Cl4 (H2O)2] Cl·6H2O [Fe Ni (Cefepime)3 Cl2] Cl3·2H2O [Co Cu3 (Cefepime) Cl7 H2O] Cl·3H2O
236,257 250
214,239,260 211,237,260 304 275 250 217,250
Methanol
Propanol
202,300,431 208,264,326 –
202,300 – 240,350 246,303 205,278 190,240 – 240,310 192,240 275 221,248,330 238 222,249,337
208,232,300 244 250,335 215,387 238,271 250 247,374 210,291,350 208,261,335 300 220,252,344 211,336 215,275,349
217,300,361 378 282 205,270 – 250,361 247,420 230,282,341 241,350 270 210,254,346 209,238,246 209,246,349
E ¼ 2:859 10−3 υmax D−1 n2 −1 M¼ 2 2D þ 1 2n þ 1
211,311,388 322 250,350 214,270,376 – 241 316 220,339 207,338 210,325 – 310 333
ð22Þ H¼
DMSO
215,236,260 270 279 –
215,256,316 270,329
x1, x2,…xn are the various empirical solvent polarity parameters:
K¼
Acetone ACN 284,333 215,283 – 250
n2 −1 n2 þ 2
J¼
D−1 Dþ2
N ¼ J−H
ð23Þ
The solvent-induced frequency shift (E) is related to υmax, which is the wave number (cm−1) of the absorption maximum of the given solvent [45]. E is the empirical solvent polarity which is sensitive to both solvent-solute hydrogen bonding and to dipolar interactions. The Kirkwood's dielectric function (K) represents the dipolar dielectric interactions and is a measure of the polarity of the solvent that depends on the dielectric constant (D) of the solvent [46]. The functions J and H have been introduced to account for non-specific solute-solvent
Fig. 9. Electronic absorption spectra of cephradine, A, and cefepime, B, in different solvents.
– – – – 252,335 – 237 – – – 211,347 210,358 –
DMF Dioxane
CHCl3 CCl4
220,270 276,382
268 –
294,334 –
206,250,326 270,316
–
264,321
–
–
240 – 250 250,350 – 206,250,310 238 215,240,350 220,270 210,250,350 259,351 231,349 350
– – – – – – – – – – – – –
250,300 256,295 – 256,316,393 256,294 255 262,293 250,350 250,333 300 225,296,362 208,262 –
– – – – – – – – – – – – –
– – – – – – – – – – – – –
275 344 282,361 276,391 287 275 276 264,350 264,322 264,376 269,348 265,334 284,348
interactions such as dispersion and dipolar effects [47]. These are related to the dielectric constant (D) and the refractive index (n) of the solvents, respectively. The functions M and N have been introduced [48] to account for the solute permanent dipole-solvent induced dipole and solute permanent dipole-solvent permanent dipole interactions, respectively. The values of the solvent parameters K, M, N, E, D and n in different solvents [49] are collected in Table 7 and the results of calculations of some compounds under investigation as a representative example are collected in Table 8. The intercept a0, and the coefficients a1, a2, …an have been calculated by multiple regression analysis. The multiple correlation coefficients (R) or MCC and the probability of variation (P) have been considered as a measure of the goodness of the fit. The high value of MCC, near one, means that a certain solvent parameter has a good correlation to the spectral shift. Alternatively, the small value near zero of the significant parameter (P) means the correlation is good. Based on one-parameter equation, the parameter (M) plays the important role for determining the spectral shifts for some cephradine complexes (Cr (2:3) at λ1, Mn (1:1) at λ3, Fe (2:1) at λ2, Co (1:3) at λ2, Zn (2:1) at λ1, Ni (1:1) at λ1, Hg (1:3) at λ2, Cd (2:1) at λ3 and FeCu (1:2:2) at λ1). Also, Fe (1:3), Co (2:1) and Ni (1:1) at both wavelengths λ2 and λ3, Cu (1:3) and Cu (4:1) at λ2, Cd (1:1) at λ1 and λ2, Co-Cu (1:3:1) at λ3, Fe-Cu (1:1:1) at λ2 and Fe-Ni (1:1:3) at λ1cefepime complexes. The relative high value of the multiple regression coefficient (R) and the lower value of the probability of variation (P) for the parameter (M) points to that the solute permanent dipole-solvent induced dipole interactions are playing the important role to explain the spectral shifts observed. However, the parameter (K) is of importance for determining the spectral shifts for cephradine and some of its complexes (Fe-Cu (1:2:2) at λ1, Cr (2:3), Cu (3:1), Cd (2:1) and Fe-Co (1:1:2) at λ2), moreover cefepime at λ2, Cd (1:1) at λ3, Hg (1:1) at both wavelengths λ1 and λ2 and Fe-Cu (1:1:1) at λ1 cefepime complexes. The relative high value of multiple regression coefficient values (R) for parameter (K) for these compounds points to that the dielectric constant is effective to explain the spectral shifts rather than the electronic character. For Mn (1:1) at λ2, Cu (1:2) at λ2, Fe-Cu (1:2:2) at λ4 cephradine complexes and Cr-cefepime (2:1) complex, the parameter (N) controlled the spectral shifts, the relative high value of multiple regression coefficient (R) for the parameter (N) for these compounds points to that solute permanent dipole-solvent permanent dipole interactions are playing the important role to explain the spectral shifts observed. The best MCC values in case of cephradine at λ2, Mn (1:1) at λ1, Ni (1:1) at λ2, Cu (3:1) at λ1 and λ3, Zn (2:1) at λ1 and λ2, Cd (2:1) at λ1, Fe-Cu (1:1:1) at λ1 and Fe-Co (1:1:2) at λ1 cephradine complexes, Also, cefepime at λ1 and λ3, Mn (2:3) at λ1 and λ2, Fe (1:3) at λ1, Fe (1:1) at λ2, Ni (1:1) at λ1, Zn (1:1) at λ1, λ2 and λ3, Cd (1:1) at λ1, Hg (1:1) at λ3 and Fe-Cu (1:1:1)
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M.S. Masoud et al. / Journal of Molecular Liquids 224 (2016) 914–929
Table 5 Solvatochromism of cephradine and its metal complexes. λmax most nonpolar solvent
νmax most polar solvent (104 cm−1)
νmax most nonpolar solvent (104 cm−1)
Δν (104 cm−1)
Solvatochromism
λ2 260 λ2 209
292 210
3.84 4.78
3.42 4.76
−0.42 −0.02
– –
λ2 300
325
3.33
3.07
−0.26
–
λ1 240 λ1 220 λ1 210
250 270 211
4.16 4.54 4.76
4.00 3.70 4.73
−0.16 −0.84 −0.03
– – –
λ2 λ2 λ1 λ2
278 270 200 300
256 300 226 301
3.59 3.70 5.00 3.33
3.90 3.33 4.42 3.32
0.31 −0.37 −0.58 −0.01
+ – – –
λ2 270
262
3.70
3.81
0.11
+
λ2 275 λ2 248
250 296
3.63 4.03
4.00 3.37
0.37 −0.66
+ –
λ2 249
253
4.01
3.95
−0.06
–
λ2 238
262
4.20
3.81
−0.39
–
λmax most polar solvent
Compounds Cephradine [Cr2 (Cephradine)3 (OH)3 H2O]3H2O [Mn (Cephradine) Cl 3H2O] HCl·2H2O [Fe2 (Cephradine) Cl5 3H2O] H2O [Co (Cephradine)3] 2HCl·H2O [Ni (Cephradine) Cl H2O] HCl·3H2O [Ni (Cephradine)2] 2HCl [Cu (Cephradine)2] 2HCl·6H2O [Cu3 (Cephradine) Cl5 H2O] HCl [Zn2 (Cephradine) Cl3 H2O] HCl·H2O [Cd2 (Cephradine) Cl3 H2O] HCl·H2O [Hg (Cephradine)3] 2HCl·6H2O [Fe Cu2 (Cephradine)2 Cl5·H2O] 2HCl·3H2O [Fe Co (Cephradine)2 Cl3 H2O] 2HCl·3H2O [Fe Ni (Cephradine) Cl4 (H2O)2] HCl·4H2O
at λ2 cefepime complexes are obtained for the parameter (E), where the solvatochromic behavior for this transition is controlled by the solvent ability to form hydrogen bonding with the solute molecules. So, one solvent parameter cannot interpret the solvatochromism for this electronic transition alone, this correlation is improved by analyzing these spectral shifts using two- and three-parameter equations. The correlation of two parameter equations with the solvent spectral shifts was studied and gave better fit to spectral shifts than one parameter fits. The solvent ability to form hydrogen bonds with the solute molecules, which is reflected by the parameter E, when combined with the parameter M in case of [Mn (1:1) at λ1, Cu (1:2) at λ2, Zn (2:1) at λ1 & λ2 and Fe Co (1:1:2) at λ1] cephradine complexes and also cefepime at λ3 and its complexes with (Ni (1:2) at λ1 & Cd (1:1)
at λ1) and N in case of cephradine at λ2 and cefepime complexes with Mn (2:3) at λ1, Fe (1:3) at λ1, Fe (1:1) at λ1, Zn (1:1) at λ1 and Hg (1:1) at λ1 & λ2 and finally K for Cd (2:1) at λ2 cephradine complex and Fe-Ni (1:1:3) at λ2 cefepime complex, the MCC values jumped to (0.631, 0.996, 0.802, 0.930, 0.550, 0.985 and 0.823), (0.954, 0.196, 0.871, 0.920, 0.910, 0.974 and 1.0) and (0.975, 0.604). Moreover, the combination of the parameter M with the parameter E for Hg (1:3) cephradine complex at λ2 and cefepime complexes with Co (2:1) at λ2, Fe-Cu (1:1:1) at λ2 and Fe-Ni (1:1:3) at λ1 and N for cephradine complexes with Cr (2:3) at λ1, Mn (1:1) at λ3 and Fe (2:1) at λ2 and also K for Co (1:3) at λ2, Cd (2:1) at λ2 and λ3 and Fe-Ni (1:1:1) at λ1 cephradine complexes and cefepime complexes with Cr (2:1) at λ1, Fe (1:3) at λ1 and λ3 and Cu (1:3). Also, the introducing of the parameter
Table 6 Solvatochromism of cefepime and its metal complexes. Compounds Cefepime [Cr2 (Cefepime) (OH)4 (H2O)4] OH·H2O [Mn2 (Cefepime)3 (OH)2 (H2O)2] (OH)3 [Fe (Cefepime)3] Cl3·4H2O [Fe (Cefepime) Cl2 (H2O)2] Cl·3H2O [Co2 (Cefepime) (OH)3 H2O] OH [Ni (Cefepime) Cl H2O] Cl·5H2O [Ni (Cefepime)2] Cl2·6H2O [Cu (Cefepime)3] Cl2·OH [Cu4 (Cefepime) Cl5 H2O] Cl·H2O [Zn(Cefepime) Cl H2O]·5H2O [Cd (Cefepime) OH H2O] OH [Hg (Cefepime)] Cl2·6H2O [Fe Cu (Cefepime) Cl4 (H2O)2] Cl·6H2O [Fe Ni (Cefepime)3Cl2] Cl3·2H2O [Co Cu3 (Cefepime) Cl7 H2O] Cl·3H2O
λmax most nonpolar solvent (104 cm−1)
νmax most polar solvent (104 cm−1)
νmax most nonpolar solvent (104 cm−1)
Δν (103 cm−1)
Solvatochromism
λ2 236 λ2 250
220 276
4.23 4.00
4.54 3.62
0.31 −0.38
+ –
λ2 256
264
3.90
3.78
−0.12
–
λ2 232 λ2 322
250 295
4.31 3.10
4.00 3.38
−0.31 0.28
– +
λ2 240
282
4.16
3.54
−0.62
–
λ2 246
256
4.05
3.90
−0.15
–
λ2 267 λ2 240 λ2 247
259 255 262
3.74 4.16 4.04
3.86 3.92 3.81
0.12 −0.24 −0.23
+ – –
λ3 310
350
3.22
2.85
−0.37
–
λ2 240
250
4.16
4.00
−0.16
–
λ2 275 λ2 237
250 254
3.63 4.21
4.00 3.89
0.37 −0.32
+ –
λ2 262
257
3.81
3.89
0.08
+
λ2 263
254
3.80
3.93
0.13
+
λmax most polar solvent (103 cm−1)
M.S. Masoud et al. / Journal of Molecular Liquids 224 (2016) 914–929 Table 7 Solvent parameters and X1 and X2 for solvents. Solvent
D
n
E
M
N
K
X1
X2
CCl4 Dioxane CHCl3 Acetone Ethanol Methanol Propanol DMF Acetonitrile DMSO H2O
2.2 2.2 4.7 20.7 24.3 32.6 18.3 36.7 37.5 48.9 78.5
1.46 1.422 1.446 1.359 1.361 1.329 1.377 1.427 1.346 1.478 1.333
32.5 36 39.1 42.2 51.9 55.5 48.6 43.8 46 45 63.1
0.22 0.20 0.21 0.18 0.18 0.17 0.187 0.2 0.18 0.22 0.17
0.01 0.03 0.29 0.65 0.67 0.71 0.622 0.67 0.71 0.66 0.76
0.20 0.22 0.36 0.46 0.47 0.48 0.46 0.48 0.48 0.48 0.49
0.4444 0.4444 0.7115 0.9300 0.9395 0.9546 0.9202 0.9597 0.9605 0.9696 0.9810
0.4300 0.4300 0.4191 0.3620 0.3623 0.3381 0.5274 0.4086 0.3496 0.4412 0.3442
E to the N parameter for cefepime at λ1 and λ2 and Fe-Ni (1:1:1) at λ4 cephradine complex and K for Ni (1:1) at λ1and λ2, Cu (4:1) and FeCu (1:1:3) at λ1 and finally the combination of the parameter K to E for cephradine at λ1 and its complexes with Fe Cu (1:2:2) at λ1 and Fe Co (1:1:2) at λ2 with higher values of MCC and lower values of variation coefficient P. For three parameters equation, the combination (E, M, N) gave high values of correlations for cephradine complexes with [Cr (2:3) at λ1, Cu
923
(1:2) at λ2, Cu (3:1) at λ1, Zn (2:1) at λ1 and Fe-Cu (1:2:2) at λ2] and cefepime at λ1, λ2 and λ3 and its complexes with Cr (2:1) at λ1, Mn (2:3) at λ1, Co (2:1) at λ1 and λ2, Zn (1:1) at λ1 and Fe-Ni (1:1:3) at λ1 as shown by its multiple regression coefficient (R) and low probability of variation (P). So, the intramolecular hydrogen bonding combined with solute permanent dipole-solvent induced dipole and solute permanent dipole-solvent permanent dipole interactions are effective parameters to explain the spectral shifts. So, the effect of intramolecular hydrogen bond is of major effect. However, such effect is absent in both, one and two parameter correlations. The addition of E to M and K leads to better results for cephradine complexes with Cr (2:3) & Cd (2:1) at λ2, Hg (1:3) & Fe Cu (1:2:2) at λ1 and Fe Co (1:1:2) at λ1 and λ2 and cefepime complexes with Ni (1:1) at λ2, Zn (1:1) at λ3, Cd (1:1) at λ1 and Fe-Cu (1:1:1) at λ2. The combination (E, N, K) gave higher value of correlations for cephradine at λ1 and λ2 and its manganese complex at λ1 and cefepime complexes with Ni (1:1) at λ1, Cu (4:1) at λ1, Zn (1:1) at λ2, Hg (1:1) at λ1 and Fe-Cu (1:1:1) at λ1 and λ2 shown by its multiple regression coefficient (R). So, the effect of intra-molecular hydrogen bonding combined with solute permanent dipole-solvent permanent dipole interactions and the polarity of the solvent given in terms of its dielectric constant are effective parameters to explain the spectral shifts. The combination (M, N, K) gave higher values of correlations for Fe (2:1) at λ2, Ni (1:1) at λ1, Ni (1:2) at λ2,
Table 8 Regression analysis data for cephradine and its metal complexes. Parameters
Cephradine Y1 = 212–218 nm
E M N K E, M E, N E, K M, N M, K N, K E, M, N E, M, K E, N, K M, N, K E, M, N, K
Cr-cephradine complex (2:3)
Mn-cephradine complex (1:1)
Y2 = 260–344 nm
Y1 = 209–222 nm
Y2 = 250–275 nm
Y1 = 211–260 nm
Y2 = 300–340 nm
Y3 = 350–361 nm
Fe-cephradine complex (2:1)
Co-cephradine complex (1:3)
Y2 = 215–279 nm
Y1 = 209–270 nm
MCC
P
MCC
P
MCC
P
MCC
P
MCC
P
MCC
P
MCC
P
MCC
P
MCC
P
0.15 0.18 0.46 0.98 0.19 0.54 0.99 0.90 0.98 0.98 1.0 1.0 1.0 1.0 1.0
0.05 0.07 0.46 0.01 0.01 0.21 0.10 0.42 0.18 0.18 0.0 0.0 0.0 0.0 0.0
0.14 0.03 0.04 0.05 0.15 0.19 0.17 0.04 0.05 0.10 0.19 0.17 0.22 0.12 0.23
0.196 0.011 0.02 0.031 0.096 0.159 0.131 0.008 0.014 0.043 0.093 0.077 0.122 0.035 0.090
0.02 0.28 0.12 0.09 0.44 0.19 0.14 0.81 0.75 0.63 0.89 0.86 0.85 1.00 1.00
0.973 0.648 0.840 0.879 0.806 0.963 0.979 0.344 0.436 0.596 0.539 0.604 0.637 0.024 0.000
0.126 0.191 0.229 0.245 0.413 0.526 0.502 0.252 0.271 0.289 0.766 0.778 0.569 0.523 0.792
0.788 0.681 0.622 0.596 0.688 0.524 0.560 0.877 0.859 0.840 0.391 0.367 0.720 0.778 0.606
0.753 0.200 0.513 0.536 0.837 0.780 0.764 0.514 0.539 0.605 0.931 0.919 0.992 0.814 0.992
0.08 0.704 0.298 0.273 0.164 0.245 0.268 0.632 0.598 0.505 0.193 0.223 0.023 0.461 0.182
0.645 0.180 0.847 0.831 0.712 0.853 0.833 0.855 0.833 0.864 0.855 0.833 0.885 0.984 1.000
0.166 0.730 0.033 0.040 0.364 0.142 0.170 0.140 0.170 0.124 0.374 0.422 0.308 0.047 0.000
0.139 0.267 0.642 0.606 0.559 0.703 0.662 0.776 0.715 0.887 1.000 1.000 1.000 1.000 1.000
0.861 0.733 0.358 0.394 0.829 0.711 0.749 0.631 0.699 0.461 0.000 0.000 0.000 0.000 0.000
0.492 0.846 0.133 0.067 0.859 0.625 0.644 0.880 0.878 0.673 0.881 0.879 0.704 0.884 0.889
0.262 0.016 0.776 0.886 0.069 0.372 0.342 0.051 0.052 0.300 0.167 0.171 0.505 0.161 0.377
0.434 0.872 0.220 0.219 0.905 0.451 0.661 0.931 0.943 0.985 0.934 0.945 0.987 0.992 0.992
0.390 0.024 0.675 0.676 0.076 0.711 0.422 0.049 0.037 0.005 0.184 0.156 0.038 0.024 0.183
Table 9 K1, K2, νvapour and correlation analysis data for cephradine and its complexes. Compound Cephradine [Cr2 (Cephradine)3 (OH)3H2O] 3H2O [Mn (Cephradine) Cl (H2O)3] HCl·2H2O [Fe2 (Cephradine) Cl5 (H2O)3] H2O [Co (Cephradine)3] 2HCl·H2O [Ni (Cephradine) Cl H2O] HCl·3H2O [Ni (Cephradine)2] 2HCl [Cu (Cephradine)2] 2HCl·6H2O [Cu3(Cephradine) Cl5 H2O] HCl [Zn2 (Cephradine) Cl3H2O] HCl·H2O [Cd2 (Cephradine) Cl3 H2O] HCl. 3H2O [Hg (Cephradine)3] 2HCl·6H2O [Fe Cu2 (Cephradine)2Cl5 H2O] 2HCl·3H2O [Fe Ni (Cephradine) Cl4 (H2O)2] HCl·4H2O [Fe Co (Cephradine)2 Cl3 H2O] 2HCl·3H2O
λ2 λ2 λ1 λ2 λ1 λ2 λ1 λ2 λ1 λ1 λ2 λ1 λ2 λ3 λ2 λ4
νvapour (cm−1)
K1
K2
MCC
r (ν, D)
r2 (ν, D)
r (ν, n)
r2 (ν, n)
35,140.804 35,606.347 33,982.013 50,097.749 205,076.8 14,800.515 4746.231 52,090.055 31,042.861 −84,369.8 33,320.669 54,970.633 47,930.231 27,600.231 26,000 23,844.850
3547.388 3088.497 8260.309 −923.213 −152,287 15,795.016 −9276.220 −7313.929 6214.090 91,001.173 −115.949 −7755.117 1565.888 282,517.8 −204,466 3195.545
1942.317 10,452.503 4463.447 −21,855.4 −39,868.2 −4095.004 17,157.965 −22,286.5 −1029.956 127,008.4 −2528.374 −2098.982 4894.775 −274,952 −50,763.5 5482.584
0.731 0.476 0.367 0.482 0.781 0.944 0.426 0.711 0.990 0.521 0.862 0.094 0.171 0.830 0.851 0.812
0.723 0.238 0.360 0.067 0.402 0.874 0.025 0.547 0.988 0.321 0.088 0.031 0.092 0.819 0.304 0.660
0.522 0.057 0.130 0.004 0.162 0.764 0.001 0.299 0.977 0.097 0.008 0.001 0.009 0.671 0.092 0.435
0.525 0.338 0.022 0.479 0.306 0.866 0.241 0.102 0.192 0.150 0.855 0.030 0.116 0.571 0.849 0.289
0.276 0.458 0.000 0.230 0.094 0.749 0.058 0.010 0.037 0.022 0.730 0.001 – 0.326 0.721 0.084
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M.S. Masoud et al. / Journal of Molecular Liquids 224 (2016) 914–929
Table 10 K1, K2, νvapour and correlation analysis data for cefepime and its complexes. Compound Cefepime [Cr2 (Cefepime) (OH)4 (H2O)4] OH·H2O [Mn2 (Cefepime)3 (OH)2 (H2O)2] (OH)3 [Fe (Cefepime)3]Cl3. 4H2O [Fe (Cefepime)] Cl2 (H2O)2] Cl. 3H2O [Co2 (Cefepime) (OH)3H2O] OH [Ni (Cefepime) Cl H2O] Cl·5H2O [Ni (Cefepime)] Cl2·6H2O [Cu (Cefepime)3] Cl2·OH [Cu4 (Cefepime).Cl5·H2O] Cl·H2O [Zn (Cefepime) Cl H2O] 5H2O [Cd (Cefepime) OH H2O] OH [Hg (Cefepime)2] Cl2. 6H2O [Fe Cu (Cefepime) Cl4 (H2O)2] Cl·6H2O [Fe Ni (Cefepime)3Cl2] Cl3·2H2O
λ3 λ2 λ2 λ1 λ2 λ1 λ2 λ2 λ2 λ1 λ2 λ2 λ1 λ2 λ2
νvapour (cm−1)
K1
K2
MCC
r (ν, D)
r2(ν, D)
r (ν, n)
r2(ν, n)
33,780.213 35,112.205 38,170.155 36,642.251 39,740.2 30,740.21 30,740.12 45,246.136 39,780.678 37,130.2 38,921.591 35,880.231 51,804.596 21,230.21 53,230.23
6895.154 4502.011 701.738 47,600.914 −912.869 51,475.731 27,326.106 −3033.030 897.101 489.494 −3178.373 −4193.821 −15,535.5 −22,426.1 13.574
3398.679 −1820.017 −10,327.8 3918.259 −218.027 6259.617 −10,388.4 −12,383.3 −1882.123 226.265 5625.351 1672.128 2599.090 −412,899 246.238
0.716 0.445 0.724 1.000 0.546 0.862 1.000 0.778 0.140 0.907 0.318 0.914 0.176 0.508 0.823
0.712 0.441 0.256 0.980 0.365 0.808 0.987 0.477 0.118 0.718 0.308 0.909 0.159 0.501 0.286
0.507 0.194 0.065 0.960 0.133 0.653 0.973 0.523 0.014 0.515 0.095 0.826 0.025 0.252 0.082
0.319 0.170 0.711 0.749 0.069 0.556 0.992 0.293 0.101 0.685 0.221 0.495 0.056 0.218 0.799
0.442 0.029 0.505 0.561 0.005 0.309 0.072 0.086 0.010 0.470 0.049 0.245 0.003 0.048 0.638
Zn (2:1) at λ2, Cd (2:1) at λ1 and λ3 and Fe-Cu (1:2:2) at λ2 cephradine complexes and also cefepime complexes (Mn (1:1) at λ2 and Cu (1:2) λ1) λ3. So, the effect of solute permanent dipole-solvent induced dipole combined with solute permanent dipole-solvent permanent dipole interactions and the polarity of the solvent given in terms of its dielectric constant are major rather than the electronic character of the substituent. So, the addition of parameter M to N and K leads to better results. Generally, it is concluded that the addition of a four solvent parameter to the three parameter equations always gave rise to improvements in the correlation with the solvent induced spectral shifts. It is of interest to search about the main physical properties of the solvents mainly in the dielectric constant and the refractive index and their contribution to affect the electronic spectral bands. So, the spectra were recorded
for each in a variety of solvents with markedly different physical properties. K1, K2, νvapour, r2 (ν, D), r2 (ν, n) and MCC are computed and listed in Tables 9–10. The data indicated that both the dielectric constant (∈) and the refractive index (n) of solvents affect the electronic absorption spectra of these compounds but with different degrees. The following equation is applied [50]
νsolution ¼ νvapour þ K1
2∈−2 2n2 −2 þ K2 2 2∈ þ 1 2n þ 1
ð24Þ
Multiple regression technique [50–51] is applied. The νvapour values and the coefficients K1, K2 was determined. Based on linear regression,
Table 11 The values of aM based on induction polarization of cephradine and its metal complexes. Compounds
Water
Ethanol
Methanol
Propanol
Acetone
ACN
DMSO
Dioxane
Cephradine [Cr2(Cephradine)3 (OH)3 H2O] 3H2O [Mn (Cephradine) Cl (H2O)3] HCl·2H2O [Fe2 (Cephradine) Cl5 (H2O)3] H2O [Co (Cephradine)3] 2HCl·H2O [Ni (Cephradine) Cl H2O] HCl·3H2O [Cu (Cephradine)2] 2HCl·6H2O [Cu3 (Cephradine) Cl5 H2O] HCl [Zn2 (Cephradine) Cl3H2O] HCl·H2O [Cd2 (Cephradine) Cl3 H2O] HCl·3H2O [Hg (Cephradine)3] 2HCl·6H2O [Fe Cu2 (Cephradine)2 Cl5 H2O] 2HCl·3H2O [Fe Co (Cephradine)2 Cl3 H2O] 2HCl·3H2O [Fe Ni (Cephradine) Cl4 (H2O)2] HCl·4H2O
0.98 0.97 0.69 0.93 0.66 2.62 0.66 0.50 1.86 1.71 0.84 1.14 1.78 0.62
0.95 0.94 0.68 0.90 0.64 2.19 0.64 0.47 1.81 1.66 0.81 1.11 1.73 0.60
0.95 0.94 0.67 0.91 0.64 2.19 0.65 0.47 1.81 1.66 0.82 1.11 1.73 0.60
0.95 0.94 0.67 0.90 0.64 2.18 0.64 0.47 1.81 1.65 0.82 1.11 1.73 0.60
1.13 1.12 0.80 1.08 0.77 2.87 0.77 0.58 2.16 1.98 0.98 1.33 2.07 0.71
1.26 1.25 0.90 1.2 0.86 2.62 0.86 0.64 2.4 2.20 1.08 1.47 2.29 0.79
1.26 1.25 0.90 1.20 0.86 1.41 0.86 0.64 2.4 2.2 1.10 1.48 2.30 0.80
0.61 0.60 0.43 0.58 0.42 2.9 0.41 0.31 1.16 1.06 0.52 0.71 1.11 0.38
Table 12 The values of aM based on orientation polarization of cephradine and its metal complexes. Compounds
Water
Ethanol
Methanol
Propanol
Acetone
ACN
DMSO
Dioxane
Cephradine [Cr2 (Cephradine)3 (OH)3H2O] 3H2O [Mn (Cephradine) Cl (H2O)3] HCl·2H2O [Fe2 (Cephradine) Cl5 (H2O)3] H2O [Co (Cephradine)3] 2HCl H2O [Ni (Cephradine) Cl H2O] HCl 3H2O [Cu (Cephradine)2] 2HCl 6H2O [Cu3 (Cephradine) Cl5 H2O] HCl [Zn2 (Cephradine) Cl3 H2O] HCl·H2O [Cd2 (Cephradine) Cl3 H2O] HCl H2O [Hg (Cephradine)3] 2HCl. 6H2O [Fe Cu2 (Cephradine)2 Cl5 H2O] 2HCl 3H2O [Fe Co (Cephradine)2 Cl3H2O] 2HCl 3H2O [Fe Ni (Cephradine) Cl4 (H2O)2] HCl 4H2O
1.71 1.08 2.82 1.42 0.50 2.01 0.64 0.34 1.85 1.46 1.81 1.70 1.75 0.32
1.66 1.05 2.74 1.38 0.49 1.95 0.62 0.34 1.53 1.42 1.75 1.65 1.70 0.31
1.66 1.05 2.74 1.38 0.49 1.95 0.62 0.34 1.54 1.42 1.76 1.65 1.70 0.31
1.66 1.04 2.73 1.38 0.49 1.95 0.62 0.34 1.53 1.42 1.75 1.64 1.69 0.31
1.98 1.25 3.27 1.65 0.58 2.33 0.75 0.40 1.83 1.69 2.10 2.18 2.03 0.37
2.20 1.39 3.62 1.83 0.65 2.58 0.83 0.44 2.03 1.88 2.32 1.06 2.25 0.42
2.21 1.39 3.64 1.84 0.65 2.59 0.83 0.45 2.04 1.88 2.33 2.19 2.26 0.42
1.06 0.67 1.76 0.89 0.31 1.25 0.40 0.21 0.98 0.91 1.13 1.06 1.09 0.20
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925
Table 13 The values of aM based on induction polarization of cefepime and its metal complexes. Compounds
Water
Ethanol
Methanol
Propanol
Acetone
ACN
DMSO
Dioxane
Cefepime [Cr2 (Cefepime) (OH)4 (H2O)4] OH·H2O [Mn2 (Cefepime)3 (OH)2 (H2O)2] (OH)3 [Fe (Cefepime)3] Cl3 4H2O [Co2 (Cefepime) (OH)3H2O] OH [Ni (Cefepime) Cl H2O] Cl·5H2O [Ni (Cefepime)2] Cl2·6H2O [Cu (Cefepime)3]Cl2·OH [Cu4 (Cefepime) Cl5 H2O] Cl·H2O [Zn (Cefepime) Cl H2O] 5H2O [Cd (Cefepime) OH H2O] OH [Hg (Cefepime)2] Cl2 6H2O [Fe Cu (Cefepime) Cl4 (H2O)2] Cl·6H2O [Fe Ni (Cefepime)3Cl2] Cl3·2H2O
0.50 1.51 1.34 0.74 1.39 1.05 0.70 1.38 0.74 1.23 1.00 3.24 0.67 0.88
0.47 1.46 1.31 0.72 1.35 1.02 0.68 1.34 0.72 1.23 0.97 3.15 0.65 0.86
0.47 1.46 1.31 0.72 1.35 1.02 0.68 1.34 0.72 1.22 0.98 3.15 0.65 0.86
0.47 1.46 1.30 0.72 1.34 1.02 0.68 1.33 0.72 1.23 0.97 3.15 0.65 0.86
0.58 1.75 1.56 0.95 1.61 1.22 0.82 0.60 0.86 1.61 1.17 3.76 0.78 1.13
0.64 1.94 1.73 0.46 1.79 1.36 0.90 1.77 0.96 1.47 1.29 4.17 0.87 0.55
0.64 1.94 1.74 0.96 1.79 1.36 0.91 1.78 0.96 0.78 1.30 4.18 0.87 1.14
0.31 0.94 0.84 0.46 0.87 0.65 0.44 0.88 0.46 1.63 0.62 2.02 0.42 0.55
Table 14 The values of aM based on orientation polarization of cefepime and its metal complexes. Compounds
Water
Ethanol
Methanol
Propanol
Acetone
ACN
DMSO
Dioxane
Cefepime [Cr2 (Cefepime) (OH)4 (H2O)4] OH·H2O [Mn2 (Cefepime)3 (OH)2 (H2O)2] (OH)3 [Fe (Cefepime)3]Cl3·4H2O [Co2 (Cefepime) (OH)3 H2O] OH [Ni (Cefepime) Cl H2O] Cl·5H2O [Ni (Cefepime)2] Cl2·6H2O [Cu (Cefepime)3]Cl2·OH [Cu4 (Cefepime) Cl5H2O] Cl·H2O [Zn (Cefepime) Cl H2O] 5H2O [Cd (Cefepime) OH H2O] OH [Hg (Cefepime)] Cl2 6H2O [Fe Cu (Cefepime) Cl4 (H2O)2]Cl·6H2O [Fe Ni (Cefepime)3 Cl2] Cl3·2H2O
1.39 1.30 1.89 3.95 1.08 0.87 1.18 2.31 1.33 1.25 1.15 0.73 0.58 2.03
1.35 1.26 1.84 3.83 1.05 0.84 1.15 2.24 1.29 1.22 1.12 0.71 0.57 1.97
1.35 1.27 1.84 3.84 1.05 0.84 1.15 2.24 1.30 1.22 1.12 0.71 0.57 1.98
1.34 1.26 1.83 3.82 1.05 0.84 1.15 2.24 1.29 1.22 1.12 0.71 0.57 1.97
1.61 1.51 2.20 4.57 1.25 1.00 1.37 2.67 1.55 1.61 1.34 0.85 0.68 2.36
1.79 1.67 2.43 5.07 1.39 1.12 1.52 2.96 1.71 0.78 1.48 0.95 0.75 2.61
1.79 1.68 2.44 5.09 1.39 1.12 1.52 2.97 1.72 1.62 1.49 0.95 0.76 2.62
0.86 0.81 1.18 2.46 0.67 0.54 0.73 1.44 0.83 0.78 0.71 0.46 0.36 1.27
the function νsolution is linear in both ∈ and n, so: νsolution ¼ νvapour þ K1 X1 þ K2 X2
ð25Þ
For simplicity, νvapour were calculated when K2 = 0 and the equation becomes as follows: νsolution ¼ νvapour þ K1
2∈−2 2∈ þ 1
ð26Þ
where νsolution values were plotted against X1 and the values of K1 and νvapour were obtained from the slopes and intercepts, respectively and also MCC were obtained. Similarly, νvapour were calculated when K1 = 0 and the equation becomes as follows: νsolution ¼ νvapour þ K2
2n2 −2 2n2 þ 1
ð27Þ
where νsolution values were plotted against X2 and the values of K2 and νvapour were obtained from the slopes and intercepts, respectively and also MCC were obtained, Also, the νsolution were plotted against K1X1 + K2X2 and data are collected in Tables 9–10, νvapour were obtained from the intercepts and MCC values were calculated using SPSS program. It was found the dielectric constant is affected more than refractive index on cephradine, cefepime and their metal complexes. X1 ¼
2ðD−1Þ 2D þ 1
ð28Þ
2 n2 −1 ð2n2 þ 1Þ
ð29Þ
& X2 ¼
3.3.3. Calculation of radius of solutes The two important and commonly used formulations for solventsolute interactions are the Born (point charge model) and Onsager (point dipole dielectric continuum model) formulations. In both models electric charges and lengths are combined to obtain the physical dimension of energy. ðiÞEion solv ¼
−q2 FðDÞ Born equation 2a
ðiiÞEdipol ¼ solv
ð30Þ
−μ 2 f ðDÞ Onsangeg equation 2a3
ð31Þ
The solvent polarity function F (D) and f (D) are dimensionless numbers as, they represent the relative strength of the electric field experienced by the ion or dipole. The reaction field model of solute-solvent interactions introduced by Onsager equation is most widely used. In
Table 15 Kamlet Taft solvatochromic parameters. Solvent
α
β
π*
CCl4 Dioxane CHCl3 Acetone Ethanol Methanol Isopropanol DMF Acetonitrile DMSO H2O
0.00 0.37 0.20 0.08 0.86 0.98 0.76 0.00 0.19 0.00 1.17
0.10 0.00 0.10 0.43 0.75 0.66 0.95 0.69 0.40 0.76 0.47
0.59 0.55 0.58 0.71 0.84 0.60 0.48 0.88 0.75 1 1.09
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Table 16 Solvent independent correlation coefficient a, b, s of the Kamlet Taft parameters for cephradine and its metal complexes. Compounds Cephradine [Cr2 (Cephradine)3 (OH)3 H2O] 3H2O [Mn (Cephradine) Cl (H2O)3] HCl·2H2O [Fe2 (Cephradine) Cl5 (H2O)3]H2O [Co (Cephradine)3] 2HCl·H2O [Ni (Cephradine) Cl H2O] HCl·3H2O [Ni (Cephradine)2] 2HCl [Cu (Cephradine)2] 2HCl·6H2O [Cu3 (Cephradine) Cl5 H2O] HCl [Zn2 (Cephradine) Cl3 H2O] HCl·H2O [Cd2 (Cephradine) Cl3 H2O] HCl·H2O [Hg (Cephradine)3]2HCl·6H2O [Fe Cu2 (Cephradine)2 Cl5 H2O] 2HCl·3H2O [Fe Ni (Cephradine) Cl4 (H2O)2] HCl·4H2O [Fe Co (Cephradine)2 Cl3 H2O] 2HCl·3H2O
λ1 λ1 λ3 λ2 λ1 λ1 λ2 λ1 λ2 λ2 λ3 λ1 λ3 λ2 λ2
νo
a
b
S
P
46,971.076 36,810.171 26,392.267 33,361.183 51,091.505 33,644.484 42,439.666 31,539.289 271.311 33,003.484 31,654.509 40,128.994 315.849 372.091 27,300.607
−357.212 −4065.842 417.575 971.598 4991.086 −6175.857 −603.690 976.288 0.729 −31.229 −3302.268 990.909 3.608 −0.325 651.214
4041.529 8296.528 −93.627 −844.640 −7041.885 11,629.463 −3114.359 2807.625 8.635 −303.727 11,090.427 744.495 2.695 −71.458 1627.872
−3531.010 11,040.334 2250.318 −704.256 −6917.424 13,896.969 −4271.932 2639.753 −2.874 540.123 14,539.420 −5246 35.115 15.862 301.683
0.000 0.141 0.000 0.000 0.526 0.425 0.631 0.176 0.000 0.541 0.676 0.739 0.266 0.301 0.319
this model; a neutral dipolar molecule is a sphere with central point dipole moment μ. The dipole produces an electric field and this field has two separate effects on the surrounding solvent molecules [52–53]: a- Induction polarization. b- Orientation polarization. In case of induction polarization, the solute-solvent interaction is given by: Esolv ¼
−μ M f ðDÞ− f n2 2a3
ð32Þ
2 n2 −1 f n2 ¼ 2n2 þ 1
ð33Þ
Eq. (33) is a measure of the permanent dipole-induced dipole interactions. The correlation of νmax and f(n2), gives a straight line with a M , where, n is refractive index and negative slope, which equals to −μ a3 M
aM is the radius of the spherical cavity which, contains the solvent molecule. For orientation polarization of the solvent dipoles, the total solvation energy is: Esolv ¼
−μ M f ðDÞ−f n2 a3M
f ðDÞ ¼
2ðD−1Þ 2D þ 1
ð34Þ
where D is the dielectric constant, [f (D) − f (n2)] is a measure of the interactions between the permanent dipoles. Solvent-solute interaction is
dependent on the properties of both the solvent, polarity of the solute and the type of the electronic transition. The solvatochromic shifts are often used to assign the transition as π-π*, n-π*or charge transfer. The slope of the plot of wavenumber against refractive index is negative with small value, which reflects a weak solvent-solute interaction due to the variation of the solvent refractive index), the dielectric constant f (D) for a number of polar solvents and [f(D) − f(n2)] for polar and non polar solvents for of the cephradine, cefepime and their complexes. M indicating The slopes for all compounds are positive and equal to −μ 2a3 that, Esolv is negative. Hence, one can conclude that the main solventsolute interaction is of dipole-dipole behavior, Tables 11–14 showed the calculated values of the radius of the spherical cavity. It was found that the radius of spherical cavity of examined compounds increased on increasing the polarity of the solvent from dioxane to water. 3.3.4. Kamlet–Taft equation This was used in order to describe the overall solvent effects, which has successfully been applied to separate the influence of non specific chemical interactions, including electrostatic effects (dipolarity/polarizability). From specific interactions hydrogen bonding is related to the molecular structure of a compound [54–57]. νmax ¼ νo þ s π þ b β þ a α
ð35Þ
where νmax is the wavenumber (cm− 1) in the maximum absorption band of the investigated compounds in pure solvents, νo the regression intercept corresponds to the gaseous of the spectrally active compounds, π* is a measure of the solvent dipolarity/polarizability, β is the scale of the solvent hydrogen-bond acceptor (HBA) basicities, α is
Table 17 Solvent independent correlation coefficient a, b, s of the Kamlet Taft parameters for cefepime and its complexes. Compound Cefepime [Cr2 (Cefepime) (OH)4 (H2O)4] OH·H2O [Mn2 (Cefepime)3 (OH)2 (H2O)2] (OH)3 [Fe (Cefepime)3] Cl3·4H2O [Fe (Cefepime)] Cl2 (H2O)2] Cl·3H2O [Co2 (Cefepime) (OH)3 H2O] OH [Ni (Cefepime) Cl H2O] Cl·5H2O [Ni (Cefepime)2] Cl2·6H2O [Cu (Cefepime)3] Cl2·OH [Cu4 (Cefepime) Cl5H2O] Cl·H2O [Zn (Cefepime) Cl H2O]·5H2O [Cd (Cefepime) OH H2O] OH [Hg(Cefepime)2] Cl2·6H2O [Co Cu3 (Cefepime) Cl7 H2O] Cl·3H2O [Fe Cu(Cefepime) Cl4 (H2O)2]Cl·6H2O [Fe Ni(Cefepime)3Cl2] Cl3·2H2O
λ2 λ1 λ1 λ2 λ2 λ2 λ1 λ1 λ1 λ1 λ3 λ3 λ2 λ1 λ2 λ2
νo
a
b
S
45,502.574 37,928.562 58,532.551 32,871.366 −1333.299 38,073.564 34,987.380 37,346.979 39,571.604 178.356 25,956.553 0.680 0.680 0.000 0.542 0.738
−771.792 2228.562 1851.350 686.013 196.105 590.698 −1814.567 808.946 3241.486 −3.358 2107.839 0.680 0.680 1.000 0.806 0.308
−3305.438 630.726 −7557.145 −1145.012 1198.085 −6962.223 – −3071.770 −594.269 43.532 −563.659 0.824 0.824 1.000 0.898 0.555
−617.560 −1737.442 −9757.014 430.094 766.685 −5081.443 7143.184 1752.271 −1869.297 59.483 3162.712 −1178.083 −1178.083 −157.258 −62.962 13.505
M.S. Masoud et al. / Journal of Molecular Liquids 224 (2016) 914–929
927
Fig. 10. Percentage contribution to the solvatochromic effects for cephradine and its metal complexes.
the scale of the solvent hydrogen-bond donor (HBD) acidities and νo, a, b, s are solvent independent constants, their magnitudes and sign provide measures of the influence of the corresponding solute-solvent interactions on the wavenumber in the maximum of electronic absorption band, which have been determined by multiple regression analysis, using SPSS statistics program. The solvent parameters [58– 61], Table 15 and the results of the multiple regressions are presented in Tables 16–17.The contribution of each parameter to solvatochromism, on a percentage basis was calculated from the values of regression coefficients, Figs. 10–11. In case of Fe (2:1) cephradine complex at λ2 and some cefepime complexes (Cr (2:1), Cu (1:3), Cd (1:1), Hg (1:1) and Co-Cu (1:3:1)), the contribution of hydrogen-bond donor (HBD, α) acidity is the highest and the solvatochromic behavior will be governed by hydrogen bonding interactions and also the high positive value of the coefficient (a) indicates a hypsochromic shift occurs with increasing solvent-hydrogen bond acidity. This conclusion implies stabilization of the ground state relative to the excited state [62]. For Co (1:3) & Fe-Ni (1:1:1) cephradine complexes and cefepime and its complexes (Fe (1:3), Co (2:1) and Ni (1:2)), the HBA effects dominate with a high negative value so, these complexes include
important contributions from the solvent HBA (hydrogen bond acceptor) basicity. Judging from the coefficient values and describes the ability of the solvent to accept a proton in solute-to-solvent hydrogen bonding, while cephradine and its complexes (Cu (1:2), Cu (3:1) and Fe-Co (1:1:2)) and cefepime complexes (Fe (1:1) and Fe-Ni (1:1:3)), the HBA effects dominate with a high positive value, which suggest the formation of solute-solvent hydrogen bonds for both electronic state, which stabilizes them in solvents with high hydrogen bond donating and low hydrogen bond accepting abilities. The small value of b in some complexes may be due to the ability of such complexes to accept hydrogen bonds have a smaller effect on λmax compared with their ability to donate hydrogen bonds. The negative sign of s for Ni (1:2) & Hg (1:3) cephradine complexes and cefepime complexes (Mn (2:3) and Fe-Cu(1:1:1)) showed a positive solvatochromism with increasing solvent dipolarity/polarizability (π* term) with higher stabilization of the electronic excited state as compared to the ground state stabilization, while some of cephradine complexes Cr (2:3), Mn (1:1), Ni (1:1), Zn (2:1), Cd (2:1) and Fe-Cu (1:2:2) and also some of cefepime complexes (Ni (1:1), Cu (4:1) and Zn (1:1) have the high positive value for the classic solvation effects.
Fig. 11. Percentage contribution to the solvatochromic effects for cefepime and its metal complexes.
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4. Conclusion There is satisfactory agreement between the dissociation constants of cephradine and cefepime determined by UV spectrometry and potentiometry. The combination of the two methods permits the direct assignment of the pKa values to the ionization enters. The electronic spectra of cephradine, cefepime and their metal complexes are affected by the nature of the solvents that differ in their properties. We can express this effect quantitatively by applying different models: mainly multiple regression and Kamlet–Taft equations. Solvation energy was defined quantitatively as energy of interaction between the solute and the solvent. References [1] S.A. Waksman, What is an antibiotic or an antibiotic substance? Mycologia 39 (5) (1947) 565–569. [2] F.V. Nussbaum, M. Brands, B. Hinzen, S. Weigand, D. Häbich, Medicinal chemistry of antibacterial natural products – exodus or revival? Angew. Chem. Int. Ed. Eng. 45 (31) (2006) 5072–5129. [3] K.C. Peach, W.M. Bray, D. Winslow, P.F. Linington, R.G. Linington, Mechanism of action-based classification of antibiotics using high-content bacterial image analysis, Mol. Bio. Syst. 9 (2013) 1837–1848. [4] A.M. Hujer, M. Kania, T. Gerken, V.E. Anderson, J.D. Buynak, X. Ge, P. Caspers, M.G.P. Page, L.B. Rice, R.A. Bonomo, Structure-activity relationships of different -lactam antibiotics against a soluble form of Enterococcus faecium PBP5, a type II bacterial transpeptidase, Antimicrob. Agents Chemother. 49 (2) (2005) 612–618. [5] F. Kees, H. Grobecker, Systematics of beta-lactams: chemical properties and structure activity relationship of oral cephalosporins, Antibiot. Chemother. 47 (1995) 1–7. [6] M. Yusof, Y.D.C. Mei, J.L. Enhui, N.M. Noor, W.W. Ab Razak, A.S. Abdul Rahim, An illustrated review on penicillin and cephalosporin: an instant study guide for pharmacy students, Webmedcentral, Pharm. Sci 2 (12) (2011), WMC002776. [7] R. Fontana, G. Cornaglia, M. Ligozzi, A. Mazzariol, The final goal: penicillin-binding proteins and the target of cephalosporins, Clin. Microbiol. Infect. 6 (3) (2000) 34–40. [8] J. Clardy, M. Fischbach, C. Currie, The natural history of antibiotics, Curr. Biol. 19 (11) (2009) R437–R441. [9] S.R. El-Shaboury, G.A. Saleh, F.A. Mohamed, A.H. Rageh, Analysis of cephalosporin antibiotics, J. Pharm. Biomed. Anal. 45 (2007) 1–19. [10] H.C. Neu, Pathophysiologic basis for the use of third-generation cephalosporins, Am. J. Med. 88 (4A) (1990) 3S–11S. [11] D.E. Low, T.M.J. File, P.B. Eckburg, G.H. Talbot, H.D. Fredland, J. Lee, L. Llorens, I.A. Critchley, D.A. Thye, A randomized, double-blinded, multicentre, phase III trial of the efficacy and safety of ceftaroline fosamil versus ceftriaxone in community-acquired pneumonia, J. Antimicrob. Chemother. 66 (3) (2011) 33–44. [12] L.D. Saravolatz, G.E. Stein, L.B. Johnson, Ceftaroline: a novel cephalosporin with activity against methicillin-resistant Staphylococcus aureus, Clin. Infect. Dis. 52 (9) (2011) 1156–1163. [13] M.S. Masoud, A.E. Ali, N.M. Nasr, Chemistry, classification, pharmacokinetics, clinical uses and analysis of beta lactam antibiotics: a review, J. Chem. Pharm. Res. 6 (11) (2014) 28–58. [14] M.S. Masoud, A.E. Ali, N.M. Nasr, Coordination chemistry and biological activity of different types of antibiotics, J. Chem. Pharm. Res. 7 (7) (2015) 64–90. [15] G. Schwartzenbach, Complexmetric Titration, 2nd Ed. Methuen young books, London, 1969. [16] I. Vogel, A Text Book of Quantitative Inorganic Analysis, Longmann, London, 1978. [17] M.S. Masoud, A.E. Ali, D.A. Ghareeb, N.M. Nasr, Synthesis and characterization of cephradine metal complexes as Alzheimer disease therapeutic agent: an in vitro kinetic study on acetylcholinesterase and monoamine oxidase, J. Chem. Pharm. Res. 5 (12) (2013) 1325–1334. [18] M.S. Masoud, A.E. Ali, D.A. Ghareeb, N.M. Nasr, Effect of some novel metallocefepime on neurotransmitter catalyzing enzymes, J. Chem. Pharm. Res. 6 (7) (2014) 1–9. [19] M.S. Masoud, A.E. Ali, D.A. Ghareeb, N.M. Nasr, Synthesis, molecular spectroscopy and thermal analysis of some cefepime complexes, J. Mol. Struct. 1107 (2016) 189–201. [20] M.S. Masoud, A.E. Ali, D.A. Ghareeb, N.M. Nasr, Structural, spectral and thermal analysis of some metallocephradines, J. Mol. Struct. 1099 (2015) 359–372. [21] M.S. Masoud, A.E. Ali, G.S. Elasala, Synthesis, spectral, computational and thermal analysis studies of metalloceftriaxone antibiotic, J. Mol. Struct. 1084 (2015) 259–273. [22] M.S. Masoud, A.E. Ali, G.S. Elasala, Synthesis, spectral, computational and thermal analysis studies of metallocefotaxime antibiotics, Spectrochim. Acta A 149 (2015) 363–377. [23] M.S. Masoud, A.G. Nassar, A.S. Abdel-Hamed, M.M. El-Dakiky, Complexing properties of some 0-dihydroxyazo compounds, Acta Chir. Hung. 129 (5) (1992) 631–640. [24] W.J. Gelsema, C.L. Deltgny, A.G. Remijnse, M.H.A. Bluleven, pH-measurements in alcohol water mixtures using aqueous and standard buffer solutions for calibration, Recueil 85 (1966) 647–659. [25] V. Evagelou, A.T. Kakoulidou, M. Koupparis, Determination of the dissociation constants of the cephalosporins cefepime and cepirome using UV spectrometry and pH potentiometry, J. Pharm. Biomed. Anal. 31 (2003) 11119–11128.
[26] M.S. Masoud, A.M. Khalil, I.I.A. El-Gawed, Electronic spectral properties & the stabilities of dinitrosoresorcinol sulfonate, Indian J. Chem. 15 A (5) (1977) 468–469. [27] A.A. Muk, M.B. Pravico, Effect of substituents on dissociation constants of picramine reagents containing the o,o’-dihydroxyazo group, Anal. Chem. Acta 45 (3) (1969) 534–538. [28] J. C. Colleter, Determination of formulas and stability constants of complexes. Study and applications of a new spectroscopic method, Ann. Chim (Paris), 5: 415–467 (1960); CA 55, 8144 b (1961). [29] K. Mui, W. McBryde, E. Neiboer, The stability of some metal complexes in mixed solvents, Can. J. Chem. 52 (10) (1974) 1821–1833. [30] A.P. Kreshkov, Present-day theory and practice of the analytical chemistry of nonaqueous solutions, Talanta 17 (11) (1970) 1029–1044. [31] J.F. Coetzee, C.D. Ritchie, Solute-Solvent Interactions, Marcel Dekker, New York, 1969 221. [32] A.M. Hamman, S.A. Ibrahim, A.A. Mohamad, N.M. Rageh, Acidity constants of some hydroxy azopyrazolopyridines in mixed aqueous-organic solvents, J. Chem. Eng. Data 38 (1) (1993) 63–66. [33] S.J. Yeh, H.H. Jaffe, Tautomeric equilibria. V. The basicities of disubstituted azobenzenes, J. Am. Chem. Soc. 81 (13) (1959) 3279–3283. [34] A.A. Abdel Gaber, O.A. Farghaly, M.A. Ghandour, H.S. El-Said, Potentiometric studies on some cephalosporin complexes, Monatshefte Fur. Chemie 131 (2000) 1031–1038. [35] J.M. Moratal, J. Borras, A. Donaire, Coordinating properties of the cephalexine antibiotic. A potentiometric study of the complexes formation between cephalexine and Co (II), Ni (II) and Cu (II) metal ions, Inorg. Chim. Acta 162 (1989) 113–119. [36] M.J. Zaworotko, H.H. Hammud, I. Abbas, V.C. Kravtsov, M.S. Masoud, Ampicillin acidity and formation constants with some metals and their thermodynamic parameters in different media. Crystal structure of two polymorphs isolated from the reaction of ampicillin with copper (II), J. Coord. Chem. 59 (1) (2006) 65–84. [37] G.B. Mohamed, M.S. Masoud, A.M. Hindawy, R.H. Ahmed, Solution equilibrium and structure of some antibiotic complex compounds, Egypt. J. Chem. 35 (2) (1992) 231–242. [38] G.B. Mohamed, M.S. Masoud, A.M. Hindawy, R.H. Ahmed, Differential pulse polarography of some cephalosporins and their degradation products, Alex. J. Pharm. Sci. 3 (2) (1989) 141–145. [39] H.H. Hammud, K.T. Holman, M.S. Masoud, A. El-Faham, H. Beidas, 1-Hydroxy benzotriazole (HOBt) acidity, formation constant with different metals and thermodynamic parameters: synthesis and characterization of some HOBt metal complexes – crystal structures of two polymers: [Cu2(H2O)5(OBt)2(μ-OBt)2]·2H2O·EtOH (1A) and [Cu(μ-OBt)(HOBt)(OBt)(EtOH)] (1B), Inorg. Chim. Acta 362 (10) (2009) 3526–3540. [40] J.C. Dearden, W.F. Forbes, The study of hydrogen bonding and related phenomena by ultraviolet light absorption: part IV; intermolecular hydrogen bonding in anilines and phenols, Can. J. Chem. 38 (6) (1960) 896–910 (38(10): 1837–1851). [41] T.S. Basu Baul, T.K. Chattopadhyay, B. Majee, Organotin complexes of 5-arylazo-8quinolinols, Polyhedron 2 (7) (1983) 635–640. [42] M.S. Masoud, G.Y. Ali, Electronic absorption spectra of substituted phenols, J. Chin. Chem. Soc. 28 (1981) 103–106. [43] E. Rusu, D.O. Dorohoi, A. Airinei, Solvatochromic effects in the absorption spectra of some azobenzene compounds, J. Mol. Struct. 887 (2008) 216–219. [44] H.S. Gold, C.E. Rechsteiner, R.P. Buck, Generalized spectral decomposition method applied to infrared, ultraviolet, and atomic emission spectrometry, Anal. Chem. 48 (11) (1976) 1540–1546. [45] N.S. Baylisis, L. Hume, Solvent effects in the spectra of benzene, toluene, and chlorobenzene at 2600 and 2000 Å, Aust. J. Chem. 6 (1953) 257–277. [46] H.H. Jaffe, M. Orchin, Theory and application UV, Spectroscopy New York, John Willy & Sons 1962, p. 182. [47] G. David, H.E. Hallam, Infrared solvent shifts and molecular interactions X triatomic molecules, CS2, COS and SO2, Spectrochim. Acta 23A (3) (1967) 593–603. [48] E.G. McRae, Theory of solvent effects on molecular electronic spectra frequency shifts, J. Phys. Chem. 61 (5) (1957) 562–572. [49] F.W. Fowler, A.R. Katritzky, R.J.D. Rutherford, The correlation of solvent effects on physical and chemical properties, J. Chem. Soc. (1971) 460–469. [50] R.W. Taft, M.J. Kamlet, The solvatochromic comparison method. 2. The .alpha.-scale of solvent hydrogen-bond donor (HBD) acidities, J. Am. Chem. Soc. 98 (10) (1976) 2886–2894. [51] C. Reichardt, Empirical parameters of the polarity of solvents, J. Angew. Chem. Int. 4 (1) (1965) 29–40. [52] K. Dwiecki, P. Gornas, M.N. Kalucka, K. Polewski, Spectral properties of propyl gallate in organic solvents and in heterogeneous environment, J. Acta. Agrophysica. 7 (1) (2006) 39–48. [53] M.S. Masoud, H.H. Hammmud, Electronic spectral parameters of the azo indicators: methyl red, methyl orange, PAN, and fast black K-salt, Spectrochim. Acta 57 A (2001) 977–984. [54] Y.H. Ebead, M.A. Selim, S.A. Ibrahim, Solvatochromic, acid–base features and time effect of some azo dyes derived from 1,3-benzothiazol-2-ylacetonitrile: experimental and semiempirical investigations, Spectrochim. Acta 75 A (2010) 760–768. [55] R.W. Taft, M.J. Kamlet, Linear solvation energy relationships. Part 4. Correlations with and limitations of the scale of solvent hydrogen bond donor acidities, J. Chem. Soc. Perkin Trans. 2 (1979) 1723–1726. [56] M. J. Kamlet, J. L. M. Abboud, T. H. Hall, J. Bodkin, M. H. Abraham and R. W. Taft, Linear solvation energy relationships.23 a comprehensive collection of the solvatochromic parameters π*,α and β and some methods for simpilifying the generalized solvatochromic equation, J. Org. Chem. 48: 2877 (1983); Linear solvation energy relationships. 6, addition to and correlations with the π* scale of solvent polarities, 44: 2599 (1979).
M.S. Masoud et al. / Journal of Molecular Liquids 224 (2016) 914–929 [57] Y. Marcus, The properties of organic liquids that is relevant to their use as solvating solvents, J. Chem. Soc. Rev. 22 (1993) 409–416. [58] M.R. Yazdanbakhsh, A. Mohammadi, Synthesis, substituent effects and solvatochromic properties of some disperse azo dyes derived from N-phenyl-2,2′iminodiethanol, J. Mol. Liq. 148 (1) (2009) 35–39. [59] M.M.M. Raposo, A.M.F.P. Ferreira, M. Belsley, J.C.V.P. Moura, 5′-Alkoxy-2,2′bithiophene azo dyes: a novel promising series of NLO-chromophores, Tetrahedron 64 (25) (2008) 5878–5884.
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[60] C. Reichardt, Solvents and Solvent Effects in Organic Chemistry, 3rd Ed Weinheim Wiley-VCH, 2003. [61] N.D. Divjak, N.R. Banjac, N.V. Valentic, G.S. Uscumlic, Synthesis, structure and solvatochromism of 5-methyl-5-(3- or 4-substituted phenyl)hydantoins, J. Serb. Chem. Soc. 74 (11) (2009) 1195–1205. [62] N. Trisovic, N. Banjac, N. Valentic, G. Uscumlic, Solvent effects on the structure-activity relationship of phenytoin-like anticonvulsant drugs, J. Solut. Chem. 38 (2009) 199–208.
